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Hormones and Behavior
Ashutosh Kumar
1,2
, Pavan Kumar
1,6
,
Muneeb A. Faiq
1,7
, Vivek Sharma
2,3,5
,
Kishore Sesham
1,6
and
Maheswari Kulandhasamy
4
1
All India Institute of Medical Sciences (AIIMS),
New Delhi, India
2
Jawaharlal Institute of Postgraduate Medical
Education and Research (JIPMER), Karaikal,
Puducherry, India
3
Government Institute of Medical Sciences
(GIMS), Greater Noida, Uttar Pradesh, India
4
Maulana Azad Medical College (MAMC),
New Delhi, India
5
Department of Physiology, Jawaharlal Institute
of Postgraduate Medical Education and Research,
Pondicherry, India
6
Department of Anatomy, All India Institute of
Medical Sciences (AIIMS), New Delhi, India
7
Dr. Rajendra Prasad Centre for Ophthalmic
Sciences, All India Institute of Medical Sciences,
New Delhi, India
Introduction
Hormones are secretions from the ductless
glands (known as endocrine glands) and special-
ized cells in the specific animal organs, which
circulate through blood to reach target destina-
tions in specific parts of the body (including the
brain) for action.
Modern view for the hormones is that a hor-
mone is any substance that acts at the cellular level
to initiate, stop, or modulate a cellular process,
and they include all chemical messengers synthe-
sized by the body that act by binding with high
affinity to target cells within the same individual.
Some scientists also consider pheromones as
hormones. Pheromones are those molecules
which act in a similar way as hormones –leave
the body of one individual to act on another indi-
vidual. The site of action can be nearby or at a
distant target.
Hormones can act via paracrine, autocrine, or
intracrine mechanisms. A hormone may act both
locally and at distant target sites traveling through
the bloodstream. To enter the brain, hormones
have to cross the blood-brain barrier (BBB)
which has differential regulation for specific hor-
mones and also come in direct contact with the
neurons in certain brain regions lacking a natural
BBB. Conversely, some hormones which are syn-
thesized inside the brain have to cross the BBB to
reach to the target sites present in the periphery. In
the brain, hormones alter neural transmission at
synapses and induce other neuroplastic changes,
which, with their concomitant action on the
peripherally present neuromuscular effectors,
influence neuro-physiological functions pertinent
to a behavior.
“Hormone”comes from the Greek word
hormon which literally meant “to set in motion,”
providing a clue for its inductive influence on the
behavior. Relation of the hormone with behavior
#Springer International Publishing AG 2018
J. Vonk, T. K. Shackelford (eds.), Encyclopedia of Animal Cognition and Behavior,
https://doi.org/10.1007/978-3-319-47829-6_476-1
is a complex phenomenon that cannot be
explained in the terms of direct causality. Both
show a kind of mutual dependence and certain
important to note intricacies. A hormone itself
doesn’t generate a behavior but creates a homeo-
static conditioning conductive for its occurrence,
i.e., it increases the chance that the organism will
show a particular behavior when physiological
and environmental conditions are optimum.
Empirical studies have shown that almost
all the aspects of behavior are influenced by
hormones –including survival, sovereignty,
circadian functions, feeding, reproduction, and
proliferation of the organisms. The specific
branch of the behavioral science devoted to
study hormonal influences on animal behavior
is known as “behavioral endocrinology.”
New advances and research updates in the
field have given “behavioral endocrinology”an
edge in explaining humoral bases of animal
behavior. An emerging concept “epigenetics”
has revolutionized this field providing the mech-
anisms for how the hormonal influences on the
behavior get tagged to the genetic structure of the
organism which not only may persist for the life
time but may also presumably pass into the next
generations. This chapter is aimed to provide a
summarized account of the basic concepts and
mechanisms, applied implications, and research
updates in “hormones and behavior.”
Hormones: Basic Handcuff
(Types and structure, sources, mechanisms of
action, physiological effects)
Types and Structure
The prototype chemical structure of the hormones
is that of a protein, but some are also peptides,
amines, or steroids. The protein, peptide, or amine
hormones are water soluble and hence cannot
enter into the cell directly; in contrast, steroid
hormones are lipid soluble and hence can enter
inside the cell directly. Lipid soluble hormones
act slow but their effects last longer than water-
soluble hormones.
Sources
Hormones are synthesized and secreted chiefly
by the endocrine organs –which are either com-
ponents of the brain or situated peripherally in
the body –and also by the specific tissue compo-
nents of the other organs such as the heart and
kidney (Table 1).
The endocrine organs and specific hormone-
secreting cells (inside the other organs) in
response to the neural stimuli (or humoral cues
released from specific hypothalamic nuclei)
release their secretions in the venous blood
draining those organs. In their further course,
from the venous tributaries, hormones reach to
the central blood channels from where through
the arterial branches they get distributed to the
target organs (including the brain).
Local Synthesis by Cortical Neurons
Certain hormones (including sex hormones)
are synthesized locally by cortical neurons in spe-
cific brain regions (in addition to their prime
secretion from endocrine organs) and get deliv-
ered through their axons to the targeted brain
regions which contain receptors for specific
hormones (Table 2). Hippocampus neurons are
known to secrete sex hormones and express their
receptors (Ish et al. 2007).
Mechanisms of Action
Biologically effective amounts of hormones
are very minute which get usually measured in
micrograms (mg, 10
6
g), nanograms (ng, 10
9
g),
or picograms (pg, 10
12
g).
A hormone other than steroid (except thyroid
hormones) attach to the receptors present on
the surface of target cells creating the hormone-
receptor complex, which in turn engages a
G protein-dependent secondary messenger path-
way (like cAMP, cGMP, diacylglycerol, Ca++,
etc.) to induce protein kinases/phosphorylases
related to specific biological events. Steroid hor-
mones, being lipid soluble, may additionally enter
into the cell to reach nucleus tagged with trans-
porters or binding protein present in the cell cyto-
plasm, where they set free from the carrier
molecule and attach to the nuclear receptors
2 Hormones and Behavior
Hormones and Behavior, Table 1 Salient animal hormones, sources, and major functions
Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
Hypothalamus Pituitary
Corticotropin-
releasing hormone
(CRH)
a,b,c
Paraventricular nuclei
(PVN)
Stimulates release of ACTH
and B-endorphin from anterior
pituitary
Adrenocorticotropic
hormone (ACTH)
b,c
Anterior pituitary Stimulates synthesis and release
of glucocorticoids
Gonadotropin-
releasing hormone
(GNRH)
a,b,c
Preoptic area; anterior
hypothalamus
Stimulates release of FSH and
LH from anterior pituitary
Vasopressin or
antidiuretic hormone
ADH or AVP
a,b,c
Posterior pituitary Increases water reabsorption in
kidney
Luteinizing
hormone-releasing
hormone (LHRH)
a
Nuclei; medial basal
hypothalamus (rodents
and primates); arcuate
nuclei (primates)
Stimulates release of LH from
anterior pituitary
B-endorphin
a,b,c
Intermediate lobe of
pituitary and throughout
CNS
Analgesic actions
Somatostatin (growth
hormone-inhibiting
hormone)
a
Anterior periventricular
nuclei
Inhibits release of GH and
TSH from anterior pituitary
inhibits release of insulin and
glucagon from pancreas
Follicle-stimulating
hormone (FSH)
Anterior pituitary Stimulates development of
ovarian follicles and secretion of
estrogens; stimulates
spermatogenesis
Melanotropin-release
inhibitory factor
(Dopamine)
a,c
Arcuate nuclei Inhibits the release of MSH
(no evidence of this peptide in
humans)
Growth hormone
(GH)
b,c
Anterior pituitary Mediates somatic cell growth
Neuropeptide
Y (NPY)
a,c
Arcuate nuclei Regulation of energy balance Luteinizing hormone
(LH)
Anterior pituitary Stimulates Leydig cell
development and testosterone
production in males; stimulates
corpora lutea development and
production of progesterone in
females
Neurotensin
a,c
Arcuate nuclei Regulation of energy balance Melanocyte-
stimulating hormone
(MSH)
c
Anterior pituitary Affects memory; affects skin
color in amphibians
Orexin A and B
a,c
Lateral hypothalamic area Regulation of energy balance/
food intake
Oxytocin
a,c
Posterior pituitary Stimulates milk letdown and
uterine contractions during birth
Thyrotropin-
releasing hormone
a,c
Paraventricular nuclei
(PVN)
Stimulates release of TSH and
PRL from anterior pituitary
Prolactin (PRL)
b,c
Anterior pituitary Many actions relating to
reproduction, water balance,
etc.
Histamine
a,c
Tuberomamillary nucleus
(also from mast cells)
Increases wakefulness,
prevent sleep
Thyroid-stimulating
hormone or
thyrotropin (TSH)
Anterior pituitary Stimulates thyroid hormone
secretion
(continued)
Hormones and Behavior 3
Hormones and Behavior, Table 1 (continued)
Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
Adrenal gland Thyroid/parathyroid
Mineralocorticoids Calcitonin (CT) C-cells of thyroid Lowers serum Ca2+ levels
Aldosterone Zona glomerulosa of
adrenal cortex
Sodium retention in kidney
11-
Deoxycorticosterone
(DOC)
Zona glomerulosa of
adrenal cortex
Sodium retention in kidney Parathyroid hormone
(PTH )
Parathyroid gland Stimulates bone resorption;
increases serum Ca2+ levels
Glucocorticoids Thyroxine or
tetraiodothyronine
(T4 )
b,c
Triiodothyronine
(T3)
b,c
Follicular cells Regulate oxidation and basic
metabolic rates in tissue;
learning associated
neuroplasticity
Cortisol
(hydrocortisone)
b,c
/
corticosterone
b,c
Zona fasciculata and
z. reticularis of adrenal
cortex
Increases carbohydrate
metabolism; antistress
hormone
Placenta
Increased carbohydrate
metabolism; antistress
hormone
Chorionic
gonadotropin (CG)
Placenta LH-like functions; maintains
progesterone production during
pregnancy
Dehydroepiandro-
sterone DHEA
Zona reticularis of adrenal
cortex
Weak androgen; primary
secretory product of fetal
adrenal cortex
Chorionic
somatomammotropin
or placental lactogen
(CS )
Placenta Acts like PRL and GH
Epinephrine or
adrenaline (EP)
b
Adrenal medulla Glycogenolysis in liver;
increases blood pressure
Pancreas
Norepinephrine or
noradrenaline (NE)
b
Adrenal medulla Increases blood pressure Glucagon
b,c
a-cells Glycogenolysis in liver
Ovary Insulin
b,c
b-cells Glucose uptake from blood;
glycogen storage in liver
Estrogen
c
Follicles (also in brain
regions like
hippocampus,
hypothalamus, prefrontal
cortex, amygdala)
Uterine and other female
tissue development Enhances
cognition, neuroprotective
Somatostatin d-cells Inhibits insulin and glucagon
secretion
Pancreatic
polypeptide (PP)
Peripheral cells of
pancreatic islets
Effects on gut in
pharmacological doses
Gut
4 Hormones and Behavior
Progesterone
c
Corpora lutea, placenta Uterine development;
mammary gland development;
maintenance of pregnancy
Bombesin
a
Neurons and endocrine
cells of gut
Hypothermic hormone;
increases gastrin secretion
Testes Cholecystokinin
(CCK)
a
Duodenum and CNS Stimulates gallbladder
contraction and bile flow;
affects memory, eating behavior
Androstenedione
c
Leydig cells Male sex characters Gastric inhibitory
polypeptide (GIP)
Gastrin
Duodenum
G-cells of midpyloric
glands in stomach
antrum
Inhibits gastric acid secretion
Increases secretion of gastric
acid and pepsin
Dihydrotestosterone
(DHT)
c
Seminiferous tubules and
prostate
Male secondary sex characters Gastrin-releasing
peptide (GRP)
GI tract Stimulates gastrin secretion
Testosterone
c
Leydig cells Spermatogenesis; male
secondary sex characters
Vasoactive intestinal
peptide (VIP)
a,c
Small intestine (also in
central and enteric
nervous system, and
nerve terminals)
Inhibits gastric acid secretion
and increases intestinal
secretion of water and
electrolytes; a neurotransmitter/
neuromodulator in CNS/ENS
Serotonin
a,c
GI tract and blood
platelets (also a
neurotransmitter in
brain)
Maintain mood, sleep, appetite,
and digestion. Regulate bowel
function and movements
CNS
Dopamine (DA)
a,c
Arcuate nuclei of
hypothalamus
Inhibits prolactin release (and
other actions)
Melatonin
a,c
Pineal gland Affects reproductive and
circadian control of bodily
functions
Serotonin (5-HT)
a,c
(also a
neurotransmitter)
Multisites in CNS
(including pineal)
Stimulates release of GH,
TSH, ACTH; inhibits release
of LH
Norepinephrine or
noradrenaline (NE)
a,b,
c
Hypothalamus (PVN)
(also as a
neurotransmitter from
locus ceruleus)
Regulates HPA axis (and other
actions)
Miscellaneous
Leukotrienes (LT) Lung Long-acting
bronchoconstrictors
Prostaglandins E1 and
E2 PGE1 and PGE2
Multiple type of cells Contraction/relaxation of
smooth muscle cells in vessels,
aggregation/disaggregation of
(continued)
Hormones and Behavior 5
Hormones and Behavior, Table 1 (continued)
Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
platelets, sensitization to pain
(and other actions)
Atrial naturetic factor
(ANF)
Atrial myocytes (heart) Regulation of urinary sodium
excretion
Klotho
c
Multiple organs Enhances cognition, protects
against aging
Arcuate nucleus
(hypothalamus)
Regulation of energy
balance
Regulation of energy balance Acetylcholine (also a
neurotransmitter in
brain)
Insulin-like growth
factor (IGF-1)
c
Bronchial epithelial cells
Hepatocytes. Also by
neuronal and
nonneuronal tissue in
brain. Cross blood brain
barrier
Regulates bronchoconstriction
and mucus secretion
Supports cell growth and
differentiation, vascular
remodeling. Neurotrophic
function in brain
Thymosin
Thymostatin
Thymocytes (thymus) Proliferation/differentiation of
lymphocytes
a
neurohormone
b
stress hormone
c
implicated in behavioral functions
6 Hormones and Behavior
(binding sites) at DNA promoter regions
for the genes assigned for forming specific
proteins (Fig. 1).
Although thyroid hormones are chemically
amine, their three-dimensional structure resemble
that of the steroid hormones and hence can enter
the cell and reach to the specific nuclear receptors
with the help of specific transporters present at the
cell membrane (facilitated diffusion) and in the
cell cytoplasm.
Hormones coordinate an animal’s physiology
and behavior by managing its bodily functions.
Hormones are functionally similar to the chemical
mediators including neurotransmitters and cyto-
kines and also interact with them in influencing
a behavior. They often function locally as the
neurotransmitters.
Hormones may synergize or antagonize with
each other in influencing a behavior. For example,
various sex hormones released during ovulation
in a female add up their effects inducing a
reproductive behavior; in contrast, the estrogen
which is followed by the progesterone in the men-
strual cycle induces opposite behavioral effects.
Endocrine System and Physiological Effects of
Hormones
Classically, the endocrine system of the body
has three main components: a brain part, pituitary
(anterior part), and target endocrine organ.
Neurosecretory cells in the brain (as in hypothal-
amus) synthesize releasing/inhibitory neurohor-
mones, which reach to the pituitary gland via
hypothalamic-hypophyseal portal system and
stimulate the pituitary gland to secrete its products
into the general blood supply of the body. Pitui-
tary hormones stimulate target cells in the endo-
crine organ to secrete specific hormones. In the
brain, the output hormone has a negative feedback
loop, regulating the brain’s secretion of neurohor-
mones. This three-tier system of control operates
for all endocrine organs in the body such as the
Hormones and Behavior, Table 2 Hormone synthesis by cortical neurons
Brain region Hormone Receptor
Hippocampus Estrogen progesterone Estrogen
Progesterone
Testosterone Testosterone
Oxytocin
Vasopressin
B-endorphin
Prefrontal cortex Estrogen, progesterone Estrogen
Progesterone
Testosterone
Oxytocin
Vasopressin
B-endorphin
Amygdala (quasi-cortex) Estrogen Estrogen,
Progesterone
Testosterone
Oxytocin
Vasopressin
B-endorphin
Anterior cingulate cortex Estrogen Estrogen,
Progesterone
Testosterone
Oxytocin vasopressin
B-endorphin
Hormones and Behavior 7
gonads and adrenal and thyroid glands, though all
hormones don’t follow the three-tier system as
those secreted from posterior pituitary (posterior
part of the pituitary is considered as extension of
the brain and secretes oxytocin and vasopressin
which have important physiological and behav-
ioral effects) and from specific cells of the brain
(other than the hypothalamus) or other bodily
organs (Table 1).
Hormones are involved in the maintenance of
physiological functions not only involved in day-
to-day activities like sleep, feeding, drinking,
etc. but also that with prolonged course of effects
like reproduction, growth, aging, immunity,
etc. (Table 1). Hormonal regulations of the phys-
iological processes have been co-opted with
the behavior linked to these processes in the
evolutionary course to ensure better survival of
the organism.
Behavioral Endocrinology As a
Discipline
History
George Montagu in 1802 had noted that songbirds
sing more at the times of the year when their testes
are larger. The first study of behavioral
endocrinology as per records was done by Arnold
Adolph Berthold in 1846. Berthold showed that
male typical behavior could be restored by
reimplanting the testes in the cockerel birds
(what they had lost following the castration). He
thought it is caused by certain substances –
androgens –secreted from the testes (Fusani
2017).
Further founding works in this field were done
by Frank et al., using domestic or laboratory ani-
mals. In 1960, the advent of radioimmunoassay
(RIA) had allowed to measure hormones in small
blood samples. RIA had revolutionized behavior
endocrinology research because it made easy to
study in living animals and to keep them alive for
further observations and follow-ups or involve
human subjects (Fusani 2017).
Commonly Used Investigations and
Experimental Methods
The concentration of hormones in the blood or
serum in the living animal can be investigated
with the immunoassays (radioimmunoassay,
enzyme immunoassay, and fluorescence immuno-
assay) and more recently high-performance liquid
chromatography (HPLC) and mass spectrometry
combined with gas chromatography (MS-GC).
The general investigations used for in vitro
Cell surface receptor
Secondary
messenger
Protein
enzymes++
Hormone
receptor
complex
Protein, peptide,
amine hormones Steroid and thyroid
hormones
Molecular
transporters
Protein synthesis
Coding of mRNAs
Hormones and Behavior, Fig. 1 Mechanisms of action a. Protein, peptide, and amine hormones b. Steroid and
thyroid hormones
8 Hormones and Behavior
determination of hormones or their receptors are
immunocytochemistry (ICC), autoradiography, in
situ hybridization, and blotting. Brain imaging
techniques (like PET scan and f-MRI) which
reveal brain activation during certain behaviors,
paired with endocrine manipulations or monitor-
ing, can provide important information about
hormone-behavior interactions (Fusani 2017).
Standard scientific approaches to experimen-
tally manipulate the hormonal production and
observe the resultant change of behavior are men-
tioned below:
Ablation: A hormone-dependent behavior disap-
pears when the source of the hormone is
removed or the hormone actions are blocked –
it is done by surgery (an endocrine organ is
removed), antagonist or blocker (hormone
receptor is blocked), or gene knockouts.
Replacement: Restoration of the missing hor-
monal source or its hormone restores the
absent behavior –it is done by hormone
implants (planted under skin), agonists or
mimics (induce signaling cascade acting on
the hormone receptor), and natural or
engineered gene mutation.
Hormone-behavior correlation: Behavior is
studied for the covariation with the changing
concentrations of the hormone.
Hormonal Homeostasis and Its Linking
to Behavior
Major hormonal centers in the body work in uni-
son in attempt to maintain a state of functional
equilibrium with each other and put an accumula-
tive influence on the neurocognitive functions,
which is reflected in the behavioral performance
of the animal. The hypothalamus in association
with the anterior pituitary and adrenal gland con-
stitutes HPA axis –the central axis in the body
maintaining neuroendocrine homeostasis. HPA
axis is extremely important for the development
of adaptive behavior –which is necessary to deal
with the stress. A parallel axis connecting the
hypothalamus and anterior pituitary to gonads
(testis in male and ovary in female) constitutes
HPG axis. In HPG axis, release/inhibitory hor-
mones are secreted from specific hypothalamic
nuclei which induce synthesis/release of stimulat-
ing/luteinizing hormones from anterior pituitary
which in turn induce synthesis/release of sex hor-
mones from the gonads (Table 1) which makes
basis of sexual and reproductive behavior in both
sexes.
Extensive connections of the hypothalamic
nuclei to the key brain regions especially that
dealing with the emotion, learning, and memory
make HPA axis crucial in behavioral
endocrinology.
Uniquely, HPA axis components don’t connect
to each other through neural pathways, but regu-
latory instructions and feedbacks between the axis
components reach through the blood. A venous
portal system from the hypothalamus carries
corticotrophin-releasing hormone (CRH), released
from the paraventricular nuclei (PVN) to the
anterior part of the pituitary (adenohypophysis)
where they stimulate/inhibit release of adrenocor-
ticotropic hormone (ACTH). ACTH in the
blood stimulates release of cortisol/corticosterone
(a glucocorticoid) from the adrenal gland cortex,
which is directly released in the veins draining this
organ and through the blood reaching to the target
destinations, which express glucocorticoid recep-
tors (GR) for action.
HPA axis mediated neuroendocrine homeosta-
sis, and consequent neural stabilization of cogni-
tive domains of the brain is largely involved in
maintenance of healthy behavior. HPA axis
responses to the stimuli are controlled by negative
and positive feedback loops running between the
HPA centers and target destinations. A positive
feedback should increase the hormonal secretion,
and vice versa a negative feedback should in turn
decrease the hormonal secretion. Though, a posi-
tive feedback loop is less common in practice than
the negative feedback loop in HPA axis regula-
tion. Final command for the feedback loops
comes from the hypothalamic nuclei (through
releasing or inhibitory hormones). Functionally,
HPA axis extends to the limbic cortex of the brain
(HPA-L axis –the limbic cortex deals with the
emotion and affective behavior and contains
amygdala, hippocampus, medial prefrontal,
Hormones and Behavior 9
insular, and cingulate cortices as chief constitu-
ents. Different limbic system components may
have varying influence on HPA axis as has been
noted between the hippocampus and amygdala
(Fig. 2) (Kumar et al. 2017a). A dysregulation of
extended HPA axis has been extensively impli-
cated in the genesis of stress-induced behavioral
pathologies (Phillips et al. 2006; Kumar et al.
2017a).
Circadian Control of Hormone-
Regulated Behavior
Specific nuclei in the hypothalamus, namely,
suprachiasmatic (SCN) and paraventricular
nucleus (PVN), regulate timed release of hor-
mones. The pineal gland is also known to main-
tain timed release of melatonin which depends
on exposure of the organism to the light (Tsang
et al. 2014). The circadian releases of the hor-
mones from the hypothalamic and pineal nuclei
are affected by the duration and intensity of the
light the organism is exposed to. The information
of the light exposure reaches to the SCN and other
hypothalamic nuclei through bidirectional
retinohypothalamic connections (Tsang et al.
2014). Pineal gland nuclei are also connected
(Tsang et al. 2014). Control of circadian rhythm
through SCN and PVN nuclei is a complex bio-
logical process which is conserved among species
and genetically determined (Andreani et al. 2015).
The molecular repertoire of the SCN has been
presented in brief in Table 3.
The molecular repertoire maintaining circadian
rhythms were found present in many bodily
organs and tissues, which together create a
complex molecular network system which gets
L-limbic lobe of brainACTH
CRH
Glu+
GR
L
H
P
A
GR
±
+
+H-hypothalamus
CRH-corticosteroid releasing hormone
P-pituitary
ACTH-adrenocorticotrophin hormone
A-adrenal gland
GR-glucocorticoid receptor
Glu-glutamate
Glucocorticoids
GR
Hormones and Behavior,
Fig. 2 Feedback
regulations at extended
HPA-L axis
Hormones and Behavior, Table 3 Molecular repertoire
of SCN
Brain and muscle ARNT like protein-1 (Bmal1)
Clock (or Npas2 in neuronal tissue)
Cryptochrome (cry) 1,2
Period (per)1,2,3
E-box
Retinoid-related orphan receptor (Ror) a,b,l
Rev-Erb a,b
Chrono
Casein kinase 1 (ck1) d,e
10 Hormones and Behavior
its central command from SCN (Hughey and
Butte 2016).
Cortisol, the HPA axis output hormone, also
follows circadian rhythm, with its peak secretion
in the morning with lesser serum values along
the day. A dysregulation of circadian synthesis/
release of cortisol was found implicated in stress-
induced psychiatric disorders (Kumar et al.
2017a,b).
Blood-Brain Barrier (BBB): A Body-Brain
Interface in Hormonal Action
Crossing Blood-Brain Barrier (BBB)
A hormone would pass through the BBB or not
depending on its chemical structure. Steroid hor-
mones are lipid soluble and hence can easily pass
to-and-fro through the BBB (the peripherally syn-
thesized hormones enter the brain and those syn-
thesized inside the brain reach to periphery), but
protein, peptide, amine, and other non-lipid hor-
mones can do it with help of the transporters/
binding proteins only. Availability of the trans-
porters/binding proteins in the blood makes
passage of lipid-insoluble hormones a saturable/
rate-limited process.
No BBB in Selective Brain Regions
Selective sites of the hormone synthesizing
brain regions called circumventricular organs are
devoid of a blood-brain barrier (BBB) which
facilitates the release of the stored hormones in
the blood (Table 4).
These BBB-free regions are also the site for
receiving peripherally released hormones and
contain receptors for such hormones –present-
ing a unique opportunity for neuron-hormone
interactions.
Neuron-Hormone Interactions Inside the
Brain
Hormone-Induced Neuroplasticity
Hormonal exposure induces adaptive plastic
changes at the neural synapses –basic unit of the
information processing in the nervous system.
The key brain regions involved in the neuroendo-
crine regulation (like amygdala, hippocampus,
hypothalamus, prefrontal and limbic cortex)
densely express receptors for the hormones impli-
cated in cognitive and emotional development
(like sex and thyroid hormones, oxytocin, and
vasopressin).
Any change in the physiological levels of a
hormone reaching the brain centers involved in a
behavior-induced structural and functional
changes at the synapses –alter membrane excit-
ability, induce synaptic protein formation and
activate membrane signaling cascade, and alter
presynaptic release of neurotransmitters and/or
response at postsynaptic membrane –in turn influ-
ences synaptic transmission. Hormonal influence
is also evidenced in the formation of the new
synapses, neurite outgrowth and spine density,
dendritic arbo rization, myelination, neural
connectivity, and other parameters of the
neuroplasticity. Additionally hormonal stimula-
tion induces release of neurotrophins, mainly
brain-derived neurotrophic factor (BDNF),
which shows neural activity-dependent secretion
in the cognitive domains of the brain and can
induce the analogous neuroplastic changes
(Kumar et al. 2017b).
Estrogen has a significant role in both sexes
in improving learning and memory acting at
hippocampal neurons which are known to synthe-
size estrogen locally and also densely express
receptors for it. These synaptic and other
neuroplastic changes are remodeled with further
hormonal level changes to reinforce or weaken a
behavior. Hormone-induced neuroplastic changes
Hormones and Behavior, Table 4 BBB free regions
in brain
Circumventricular organs
1. Organum vasculosum of lamina terminalis
2. Subfornical organ
3. Subcommissural organ
4. Median eminence (hypothalamus)
5. Intermediate lobe of pituitary gland
6. Posterior pituitary
7. Pineal gland
8. Area postrema (4th ventricle)
Hormones and Behavior 11
supposedly create a basis for such more changes
in future –a neuroscience concept known as
“meta-neuroplasticity”(Salma 2014). Behavior-
specific neural networks get hormonal modulation
when challenged with specific stimuli. Release of
a hormone in response of a stimulus is orches-
trated by specific hypothalamic nuclei –which is
the command center for the synthesis/release of all
hormones. Hormones specifically induce synthe-
sis/release of various neurotransmitters/modula-
tors in different parts of the brain. Unique of
the steroid receptors present in the brain is that
they may be activated by the neurotransmitters
and intracellular signaling systems other than
the cognate hormone by a process known as
ligand-independent activation (Blaustein 2004).
Together these molecules differentially modulate
the components of the synaptic transmission and
neural network properties. A hormone-induced
neuroplasticity is specific and unique to the indi-
viduals which brings diversity in their behavior,
i.e., two individuals may behave differently even
in the similar environmental contexts.
Cortical and Subcortical Control
Hormones show region-specificinfluence on the
cerebral cortex. The reflex-based, primitive and
instinctual, emotional, and survival behaviors
(fright, flight, fight!) which are common to all
animals depend more on the control of the hor-
mones and involve cortical regions which are
older in evolution like the hippocampus and den-
tate gyrus, olfactory cortex, and medial prefrontal/
orbital and cingulated cortex. In contrast, execu-
tive behaviors like thinking, strategizing or plan-
ning, and decision making –which are salient
characteristics of human –show less hormonal
influence and involve newly evolved cortical
brain regions like lateral prefrontal and associa-
tive regions of the neocortex.
The amygdala –a quasi-cortical structure
which is the nodal brain center for the primitive
behaviors like fear, rage, and anger and densely
expresses receptors for many hormones like
steroid (especially sex hormones and cortisol)
and amine hormones, and also for oxytocin
and vasopressin –shows high influences of the
hormones.
Hippocampal neurons (including dentate
gyrus) not only densely express receptors for the
above named hormones but are also known
to synthesize some sex hormones de novo
(Table 3), especially estrogen (Ish et al. 2007).
Synthesis of sex hormones in the hippocampus
and expression of their receptors in this and other
cortical brain regions are considered important for
the sex-specific differentiation of the brain during
embryonic development. Hormonal influence in
the hippocampus is believed to contribute more
than any other brain region owing to wider impact
of the hippocampal functions in behavior. The
hippocampus is the nodal region for learning
and memory and also maintains functional con-
nectivity with other brain regions. Estrogen is
neuroprotective and contributes substantially to
the hippocampal functions, particularly by induc-
ing structural plasticity at synapses. Testosterone,
oxytocin, and vasopressin also improve the hip-
pocampal functions (in contrast, cortisol improves
the hippocampal functions in acute exposure but
diminishes in chronic exposure). Oxytocin recep-
tor signaling in hippocampal neural circuits is
thought to mediate discrimination of social stimuli
and affiliation or avoidance behavior guiding
social recognition (Raam et al. 2017).
Hormones also influence hippocampal
neurogenesis –which has been evidenced to
keep going lifelong (in dentate gyrus) and said to
facilitate inclusion of new information –and
hence bear an important role in learning and
memory, and a dysregulation of this has been
implicated in genesis of psychiatric disorders
(Kumar et al. 2017a,b). Hormonal influences
on parahippocampal brain regions, especially
of testosterone, are known to improve spatial
performances.
Specific hypothalamic nuclei secrete hormones
which reach to various target centers inside the
brain and periphery through blood streams and
induce release of a distinct set of hormones/neu-
rotransmitters/modulators. Hypothalamic nuclei
are also intricately connected to the cortical, sub-
cortical, brain stem nuclei and spinal autonomic
centers through the nerve fibers. Thus at specific
hypothalamic nuclei, neural feedbacks integrate
and balance with that derived from the hormones
12 Hormones and Behavior
running in the circulatory system which helps the
organism to respond to the internal cues like food,
sex, or body temperature. For illustration, in hun-
ger or satiety, specific hormones are released from
the endocrine glands in the digestive system into
the draining veins which are further carried to the
parts of hypothalamus through the blood. In the
hypothalamus, specific nuclei groups further
transmit the impulses to the cortical neurons to
create a conscious awareness of feeding status of
the organism.
A miniature reign like neural structure located
at the posterior limit of the hypothalamus –the
habenula –which connects subcortical gray mat-
ter structures to the brainstem centers containing
aminergic nuclei is known to implicate in the
learning of the adaptive behavior (Kumar et al.
2017c). Habenular pathways get also influenced
by the HPA axis hormonal changes which is said
to be instrumental in the pathological develop-
ment of submissive behaviors like social defeat
(Kumar et al. 2017c).
Aminergic Release from the Brain Stem and
Hypothalamic Nuclei: A Closer Function as
Hormones
The specific nuclear groups in the brain stem
secrete aminergic/cholinergic molecules which
are released at target sites in different brain
regions through axonal endings (Table 5).
These molecules have the similar influences
on the synaptic processing as blood-running
hormones and are referred to as neurohor-
mones, though some of them can work like
neurotransmitters (or neuromodulators) –as dopa-
mine, serotonin, noradrenaline/norepinephrine,
and acetylcholine (Tables 5and 6). Some of
these molecules are also synthesized in the hypo-
thalamic nuclei –as dopamine, serotonin, and
histamine. These aminergic centers have wide-
spread reciprocal connections in the brain and
have crucial involvement in controlling neural
networks involved in emotional, survival, and
adaptive behavior of the animal. The brain stem
aminergic molecules in association with that
released from hypothalamic nuclei help in
maintaining consciousness and keeping the
organism alert and also influence circadian control
of feeding and sleep behavior.
Setting of Moods, Emotions, and Impulses
Hormones influence information transmission
speed at the synapses which provide a neural
substrate for the mood, emotions, and impulses
in the organism. The synthesis and release of the
hormones are stimulated or suppressed by the
environmental cues, i.e., a prolonged exposure
of the organism to a favorable environment
induces synthesis/release of the particular hor-
mones necessary to promote a behavior suitable
to the context. For example, when an animal is
kept in contact with a potential mate, synthesis
and release of the sex hormones will show an
upsurge. Similarly, exposure to a rival will
upsurge release of testosterone and stress
Hormones and Behavior, Table 5 Aminergic/choliner-
gic secretion by brain stem neurons
Amines
Norepinephrine –locus ceruleus, ventral tegmental
area (VTA)
Epinephrine –reticular formation (along motor nuclei
in the floor of 4th ventricle) and in periaqueductal gray
Serotonin –raphe nuclei
Dopamine –substantia nigra, ventral tegmental area
(VTA)
Choline
Pedunculopontine nucleus (PPN) –acetylcholine
Hormones and Behavior, Table 6 Types of neuronal
secretions in brain
A neurotransmitter
Is released at synapses
Passes through synaptic cleft to affect postsynaptic
neurons, a muscle cell, or another effector cell
A neuromodulator
Affects groups of neurons or effector cells with
appropriate receptors
Often acts through second messengers and can
produce long-lasting effects
A neurohormone
Is released into the blood and therefore may exert its
effects on distant peripheral targets
Hormones and Behavior 13
hormones –which are implicated in combating
behavior.
Both male and female sex hormones by
influencing release of neurotransmitters/modula-
tors like dopamine and serotonin make an impact
on mood and emotion driving an individual into
reproductive behavior. A cyclical change of sex
hormones during menstruation in female is asso-
ciated with the mood changes/swings; women
report enhanced mood in part of menstrual cycle
when estrogen will have higher secretion and vice
versa (Dreher et al. 2007). Some mood disorders
like premenstrual or postnatal depression and
perimenopausal depression (or psychosis) signify
influence of estrogen in maintenance of mood in
female. In male, high serum testosterone has been
associated with increased concentration, visual
acuity and geo-spatial abilities, positive mood,
and also with the rage and impulsive behavior.
Endogenous opioids, which are physiologically
secreted during heavy exercise or the habitual
strenuous physical activities, increase threshold
for the pain and create a euphoric feeling. Inter-
nally secreted hormone-like molecules in the
brain –neurohormones –which work like
neuromodulators and some as also neurotransmit-
ters (dopamine, serotonin, noradrenaline) have a
critical role in setting and maintenance of the
mood (Table 7).
An intricately regulated cocktail of neurohor-
mones is said to control the rate, rhythm, cou-
pling, and synchronization of the cortical
oscillatory waves in the neurocognitive networks
of the brain –which is crucial for setting and
maintenance of the mood.
Oxytocin and vasopressin which are secreted
from posterior pituitary during labor and
breastfeeding in female, and during sexual inter-
course and intimate behavior in both the sexes, are
known to have positive effect on mood and emo-
tion. Oxytocin has a higher secretion in female
and vice versa, vasopressin witnesses higher
secretion in male, and their effects have been
known to match to estrogen and testosterone,
respectively.
Autonomic Nervous System (ANS)-
Hormone Cross Regulation
ANS comprises of sympathetic and parasympa-
thetic limbs that are involved in the antagonistic
components of the behavior –crucial for the
development of sexual and adaptive behavior in
the organisms. ANS plays a central role in the
genesis of psychological and pathophysiological
stress and control of animal behavior, by being
intricately involved in the regulation of neuroen-
docrine balance, neuroeffector communication,
and behavioral response of the individual. Sym-
pathetic and parasympathetic activations are asso-
ciated with release of specific hormones inside the
brain and also from the peripheral endocrine
organs. Sympathetic nerves release adrenaline/
epinephrine which has an activational role in
fight-flight behavior and also increase heart rate
acting at sinoatrial (SA) node; in contrast, para-
sympathetic nerves release acetylcholine which
has calming effect and also decrease the heart rate.
Adrenaline/epinephrine is secreted from the
adrenal medulla (which contains developmentally
migrated sympathetic ganglions) in response to
the neural stimulus reaching to it through sympa-
thetic nerves. Both components of the ANS
engage distinct sets of the hormones,
Hormones and Behavior, Table 7 Neurohormones
Corticotropin releasing Thyrotropin
releasing
Hormone (CRH) Hormone
Gonadotropin releasing Histamine
Hormone (GNRH) Vasopressin or
antidiuretic
Luteinizing hormone releasing Hormone)
Hormone (LHRH) ADH or AVP
Somatostatin (growth hormone-
inhibiting hormone)
Oxytocin
Norepinephrine
Dopamine
Melanotropin release Serotonin
Inhibitory factor (dopamine) Melatonin
Neuropeptide Y (NPY) B-endorphin
Neurotensin Agouti-related
protein (AGRP)
Orexin A and B Estrogen
14 Hormones and Behavior
neurotransmitters, and modulators to execute their
effect. Hypothalamus is the master regulator of
the ANS integrating the influences of all the con-
tributory components and mechanisms.
Gut Hormones: Influence on Behavior
The hormones secreted in the gut (Table 1) not
only have regulatory roles in feeding behavior,
i.e., control hunger and appetite, but are also
involved in maintaining mood and emotion,
which has given rise to the concept of gut-brain
axis. The gut-brain axis gets influenced by the
common hormones (or hormone-like molecules)
which are secreted in the gut as well as inside the
brain –like peptide hormones (especially neuro-
peptide Y) and serotonin. The gut-brain axis is
also influenced by the enteric nervous system
(ENS) –which is predominantly autonomic in
function. ENS in concert with the gut hormones
helps to maintain the mood and emotion which
will have a direct impact on the behavior of the
organism –a dysregulation of gut hormone-ENS
found implicated in many behavioral pathologies
(Zhou and Foster 2015). Interestingly, human
studies support influence of gut microbiota on
behavior involving gut hormone-ENS (Skibicka
and Dickson 2013).
Hormonal Induction of Behavior:
Underlying Mechanisms
Animal behaviors range from simple reflexive
actions like withdrawal of the limb when touched
with a prick or hot stick to a complex action like
responding to the advances of a potential mate, the
human-specific behaviors like playing a musical
note, or responding to the offers of a business
partner. Hormones have an influence on almost
all aspects of animal behavior with the greater
impact on that related to the species survival and
proliferation like feeding and reproductive behav-
ior and dealing with the threats to life and self-
respect. (In Table 1hormones implicated in vari-
ous aspects of the animal behavior are indicated in
superscript “c.”)
A hormonal influence on behavior depends on
multiple factors, viz., age, sex, built, genetic
makeup, developmental history, and early-life
experience of the individual, also on the environ-
mental context, duration of exposure to the stim-
uli, and associated rewards or threats. Hormone-
driven behaviors such as sexual arousal and mate
seeking, aggression to sexual opponent, response
for food when hungry, etc. are conserved in ani-
mal kingdom and can be reproduced in the
matching environmental and personal context
(in contrast to the intellectually driven behaviors,
which are specific to human and contain less
hormonal influence and show more inter-
individual variation).
A single hormone bears impact on many types
of behaviors, or more appropriately a set of hor-
mones together determine a particular behavior.
A hormone’sfinal influence on behavior depends
on the type and expression of the cognate recep-
tors present on the target structures in the central
and peripheral nervous system, which in turn
depends on the encoding genes and their isoforms
(Pfaff 1997; Maney 2017).
Hormones have two kinds of effect on the
institution of behavior –“organizational”and
“activational.”“Organizational”effect of the hor-
mones is set during the development of the brain,
and it determines the future response of the indi-
vidual to the stimulus. In contrast, “activational”
effect depends on the current status of the hor-
mone in the body and determines immediate
response.
Most of the hormones which are implicated in
behavioral functions are either produced by neu-
ronal tissue or by the components of central neu-
roendocrine axis regulating behavior –HPA/HPG
axis. In exception, some hormones –such as
growth hormone (GH) secreted from anterior pitu-
itary, thyroid hormones, and a newly known hor-
mone Klotho, which is secreted from multiple
animal organs (chiefly kidney, liver, skin) (Dubal
et al. 2014), which are chiefly meant for somatic
functions –have also been implicated in behav-
ioral functions improving cognition (Table 1).
Hormone-behavior interaction is bidirectional,
i.e., both can induce each other. The mutual
dependency of the hormone and behavior
Hormones and Behavior 15
provides conceptual basis for the behavioral cor-
rections with therapeutic hormone manipulations
and vice versa and hence constitutes a fundamen-
tal concept in the “behavioral endocrinology.”
Genetic and Epigenetic Mechanisms
Hormone-driven behavior is hardwired in the
genes and is seen grossly conserved across the
animal kingdom. Any interindividual variation is
attributed to the different gene isoforms for the
hormones and their cognate receptors existing in
the species population. Though, it is known to
vary with the developmental history, early and
current life experiences of the individual, which
are not explained with any genetic theory. In
recent years, a new concept “epigenetics”has
been put forward to explain such lifetime varia-
tions in the hormone-driven behavior, which is
defined as “a change in the DNA structure of an
organism without introducing any change in its
code sequence.”Such epigenetic changes in the
DNA are environment induced and brought about
by the chemical tagging of the DNA bases by
methylation, or there can be changes in the
DNA packaging material like histone proteins
(methylation/acetylation) or in the methyl-
binding proteins or through noncoding RNAs
(micro-RNAs and long ncRNAs) (Cao 2014).
Hormone-induced sexual differentiation of the
developing brain and its impact on adult sexual
behavior and also infant-mother interactions and
other early-life experiences which may have grave
impact on the future behavior as an adult are
mediated through epigenetics. Though epigenetic
mechanisms introduce environment-induced
adaptive changes in the genomic structure of the
organism, by a default mechanism, most of the
epigenetic changes (gathered by an individual
either during embryonic development or through
personal life experiences) do not carry forward in
the offspring and get erased during gametogenesis
(Hackett et al. 2013). Pertinent here is to mention
that certain epigenetic changes as that created
from severe chronic stress (involving HPA axis)
may pass into next generations bypassing the
default erasure –the phenomenon is called “trans-
generational epigenetics”(Hackett et al. 2013;
Jensen 2013). Epigenetics is considered to be
instrumental in stress-induced alterations in HPA
axis settings and their consequent effects on
neurocognitive functions.
Institution of Social Behavior in a Newborn
How social behavior is instituted in a newborn is
not well understood. Supposedly, a newborn
learns how to behave interacting with the environ-
mental cues (although some of the newborn
behaviors are innate and conserved –like crying
just after birth, frequent startling, and exploratory
behavior such as putting things in mouth). Empir-
ical studies suggest that mother’s hormones in the
breast milk bear impact on a newborn’s learning
of the behavior (Grey et al. 2013). This observa-
tion has applied importance that any exogenous
intake of hormones –like anabolic steroids –by
the mother may be a hindrance to this learning.
Excess glucocorticoids (mainly cortisol) released
during stress in pregnant mother were found to
have pathological impact on programming of
HPA axis and consequent learning of behavior in
fetus (Kinsella and Monk 2009).
Hormonal Disruption in Developing Fetus:
Residual Effect on Adult Behavior
Many chemicals released from artificial sources –
industrial effluents and pesticides, heavy metals
and plastics, and natural sources –derived from
plant products, phytogens, when entered into
the body as contamination, act as decoy
ligands which hijack some components of the
biological actions of the original hormones. Such
chemicals are called hormone disruptors or
endocrine-disrupting chemicals (EDCs) (Barrett
and Patisaul 2017). Environmental estrogens and
phytoestrogens are the prime hormone disruptors,
known to affect neurocognitive domains in devel-
oping fetus, disrupting HPA/HPG (gonadal) axis,
in turn affecting institution of behavior. Loss of
behavior will be noted not only for sexual and
reproductive domain in affected fetus as adult,
but normal intelligence and memory and social
behavior may also get compromised.
Hormonal Correlates of Homosexual Behavior
Homosexual behavior is known in human from
archaic times and can be seen in many animals
16 Hormones and Behavior
also. A scientific theory supporting the biological
basis of homosexuality suggests that it has an in
utero origin linked to prenatal overexposure of the
fetus to an opposite sex hormone (Rice et al.
2012). Developing fetus faces a contrasting situa-
tion in utero, and maternal and fetal hormone
levels adjust for the better survival of the fetus
(Rice et al. 2012). Although both sex fetuses get
exposed to both kinds of sex hormones normally,
in certain cases, a sex hormone may dominate on
others helping the survival, which may or may not
be matched to the sex of the fetus. A contrasting
exposure of a developing fetus to a sex hormone is
proposed to influence its sexual behavior after-
ward as an adult, i.e., in utero exposure of a male
fetus to estrogen-predominating environment may
influence its sexual orientation in adult, and vice
versa may be true for the testosterone exposure to
a female fetus (Rice et al. 2012).
In an alternative view, a same sex hormonal
predominance in the uterus for a pregnancy
(necessitated for the survival of a particular sex
fetus) may get tagged in the genome of the mother
to get reactivated in subsequent pregnancies
(through a phenomenon called epigenetics) and
may influence in utero development of next oppo-
site sex fetuses (Rice et al. 2012). A reversed
2D/4D ratio also was found predictive of homo-
sexual behavior in the men (Xu and Zheng 2016).
Hormone-Induced Behaviors: A Brief
Overview
Survival and Adaptive Behavior
HPA axis hormones like CRH, ACTH, and
cortisol and other hormones like arginine
vasopressin –from posterior pituitary –and
adrenalin/noradrenaline from adrenal gland are
secreted in response to the acute and chronic
stress (Table 8).
HPA axis hormones are implicated in the
mechanism of avoidance learning and escape –
an adaptive behavior. Release of the stress hor-
mones is associated with concomitant activation
of the sympathetic system which adds up into the
effect. Release of stress hormones in acute stress
helps the organism to prepare for the flight or fight
behavior (both of these bear survival values for
the organism and constitute adaptive behavior).
Conversely, the chronic exposure to the stress
leads to abnormal forms of the behavior –like
anxiety, panic, and depression –mediated by key
molecular cascades like immediate early genes at
synapses induced by persistently raised levels of
the stress hormones (Senba and Ueyama 1997;
Kozlovsky et al. 2008).
Sexual and Reproductive Behavior
Sex hormones bear an exclusive influence on sex-
ual orientation and drive of the animals including
human. Both testosterone and estrogen are
secreted in each sex, former being dominating in
male and latter in female. Testosterone is convert-
ible into secondary male hormones and also estro-
gen with the action of aromatic enzyme alpha-
reductase in the brain and in periphery. Secondary
male sex hormones are essential for the develop-
ment of secondary sexual characters during
puberty, and conversion of testosterone to estro-
gen by aromatization in medial preoptic nuclei
of hypothalamus is obligatory for sexual motiva-
tion in males (Balthazart 2017). Different
brain regions bear the receptors for sex hormones,
especially that involved in maintaining
neurocognition –the prefrontal and limbic cortex
(including the hippocampus), hypothalamus, and
amygdala (Blaustein 2004). Dimorphic sexual
behavior is regulated by sex hormones-directed
modular gene expression in these brain regions.
Various components of sexually dimorphic
behaviors are governed by separable genetic pro-
grams, i.e., single genes control the specific
Hormones and Behavior, Table 8 Hormones of stress
CRH "Glucagon- "
AV P "Insulin #
ACTH "glucocorticoids "(cortisol,
corticosterone)
Angiotensin-
"
GnRH #
Epinephrine "GH "
Norepinephrine "Prolactin "#
Endorphin "Thyroid
hormones#
Hormones and Behavior 17
components of the male/female sexual behavior
(Xu et al. 2012).
Sex hormones induce an immediate sexual
drive –while effects of testosterone are more
robust and may induce aggression, the effects of
estrogen are comparatively modest. Both hor-
mones induce sex-specific behavioral and physi-
cal characteristics, as evidenced in diseases with
sex hormone dysfunction and experimental stud-
ies in the animals. Male teens with androgen
insensitivity syndrome in which dysfunction lies
at the testosterone receptor have been shown to
bear female-like physical and psychological
characteristics, including sexual orientations and
preferences. In contrast, in cases of in utero
early testosterone exposure of a female fetus in a
twin pregnancy (when another fetus is a male) or
in case congenital adrenal hyperplasia (CAH)
which may bring some masculine features in
the female child and may also reflect in the
behavior –showing characteristics of a male typ-
ical behavior. A sex-specific change of behavior
also got noted in empirical studies involving ani-
mal models where either testis or ovary was cas-
trated; conversely, the change of behavior got
undone with reimplant of the removed gonad.
Sex hormones bear wider impact on interper-
sonal relationship involving opposite sexes.
Cyclical change of the sex hormones in female
are said to influence sexual behavior which might
be reflected in interpersonal relationships. How-
ever, studies are lacking to support if same phe-
nomenon is also occurring in the male. Though
diurnal and periodic variations of the testosterone
have been noted, corresponding changes in sexual
behavior is not much defined in male animals,
with exception of rabbits (in which a cyclical
variation has been noted) (Degerman and
Kihlström 1961). In male animals, alterations in
sex hormone levels and accompanied sexual drive
are limited by exposure to the female, freedom to
intimacy, and engagement or abstinence from the
sexual activities. Seasonal or annual surge of sex
hormones is common in animals with exception
of the highest rank primates including human –
in whom there is no such fixed pattern. The cyclic
or periodic changes of sex hormones may be
associated with sexual urge and fantasies and
self-stimulating/gratifying practices. A periodic,
seasonal, or annual surge in secretion of sex hor-
mones is controlled by the releasing and stimulat-
ing hormones from hypothalamic and pituitary
centers, respectively (Table 1).
Other than the sex hormones, posterior pitui-
tary oxytocin and vasopressin are also noted to
involve in sexual and reproductive behavior
(discussed elsewhere in this chapter). Uniquely,
an anterior pituitary hormone prolactin which is
generally known to be associated with infant-
parent bonding has also been found to be associ-
ated with the heterosexual pair bonding and its
variation in secretion found to correlate with the
amount of sexual behavior and contact affiliation
in both sexes (Snowdon and Ziegler 2015).
Aggressive and Violent Behavior
Empirical studies present evidence for causal
association of testosterone in aggressive and vio-
lent behavior though a causal association has been
challenged putting forward counter argument that
aggressive/violent behavior is a by-product of
testosterone’s impact on individual’s concern for
gaining higher social status (Eisenegger et al.
2010). Sex violence by males has been almost
exclusive and also correlated positively with
serum testosterone levels (Studer et al. 2005).
Testosterone is also found linked to incidences
of aggressive behavior and violence by gun
owners (Klinesmith et al. 2006).
Unethical Behavior
Empirical studies have supported that a combina-
tion of the testosterone and cortisol may drive the
subject into unethical behavior (Lee et al. 2015).
Testosterone is said to influence a person’s drive
to acquire status-bearing resources (money,
power, leadership, etc.) which gets further inten-
sified by cortisol. Cortisol is released essentially
in reaction to a stress and may be raised in a moral
conflict leading to the mental strain, and it was
found to associate with the reward-seeking and
fear-reducing influence of the testosterone in stud-
ies (Lee et al. 2015). Individuals were found to
have lower serum levels of cortisol after commit-
ting unethical behavior as the commission of the
18 Hormones and Behavior
act perhaps had given them a sense of relief from
the mental strain (Lee et al. 2015).
Oxytocin: A Molecular Mediator of Positive
Behavior and Bonding
(Maternal behavior, sexual intimacy, romantic
love, generosity, trust, ethical and spiritual
behavior)
Oxytocin is the hormone in which most of the
behavioral endocrinologists show particular inter-
est. The physiological functions of oxytocin in
breast milk ejection during child feeding, and its
copious release during sexual intercourse and
childbirth, are known since long. Oxytocin’s role
in maternal behavior is outstanding. A study noted
induction of maternal behavior in virgin rats after
intracerebroventricular injection of oxytocin
(Pedersen et al. 1979).
Contemporary research has established its sub-
stantial role in intimate and positive aspects of
behavior (Kosfeld et al. 2005; Insel 2010).
In consecutive studies along the years, oxytocin
has been strongly implicated in the peer bonding,
romantic, and intimate relationship (Insel 2010),
and many positive aspects of behavior such as
trust, ethics, spirituality, and generosity (Kosfeld
et al. 2005; Van Cappellen et al. 2016). A study
implicated it in inducing an altruistic behavior in
social groups against the ethnic backdrops (Marsh
et al. 2017). Studies also implicated its determin-
ing role in the economic behaviors –such as in
building the trust of the customers in the investors
(Kosfeld et al. 2005).
Though having a substantial role in social
behavior, all is not fascinating about this mole-
cule. A study implicated it in some negative
aspects of behavior as well, like doing a bias in
favor of a social group to which individual
belongs (Shalvi and De Dreu 2014). Further, an
oxytocin-mediated behavior was found to be dose
dependent and inducing at optimum serum/CSF
concentrations only –violation of which may
show contrasting behavioral effects, making its
pharmacological exploitation for behavioral cor-
rections difficult (Zhong et al. 2012; Bales et al.
2013). Furthermore, oxytocin is a biological
mediator and facilitator of a positive behavior
but cannot generate itself, which limits its
pharmacological use for this purpose. After all,
expanded understanding of the oxytocin-
mediated biological mechanisms has now brought
the opportunity for the behavioral interventions
aimed at inducing the positive behavior and bond-
ing in various applied conditions.
Personality Trait Association
Personality hormone association has not been a
defined one, though unconfirmed descriptions of
high testosterone and thyroid hormone associa-
tion to certain personality traits being competitive,
focused, and aggressive can be found in the liter-
ature. Plasma oxytocin level was found positively
correlating with extravert behavior in studies
(Bendix et al. 2015). Uniquely, an anthropological
measurement comparing the length of the 2nd and
4th digits of the hands (2D/4D ratio), which is
believed to reflect the prenatal testosterone/andro-
gen exposure of the fetus, was found associated
with sex-specific behavior as the adults (Galis
et al. 2010; Xu and Zheng 2016). A lower
2D/4D ratio was found correlating with a more
male typical behavior and vice versa was found
true for a more female typical behavior.
A mismatched prenatal exposure of the sex hor-
mones have been associated with the borderline
personality disorders.
Pathological Behavior
Studies implicated hormones in the genesis of
pathological behavior like gambling, drug addic-
tion, and obsessive-compulsive disorders (OCD)
such as compulsive stealing, binge eating, etc.
HPA axis hormones are implicated in chronic
stress-induced genesis of psychiatric disorders
such as major depressive illness, bipolar disorder,
schizophrenia, and PTSD (Kumar et al. 2017b).
Chronic stress permanently alters the HPA axis
regulation resulting in a persistently increased
level of cortisol, creating basis for the pathogene-
sis of such psychiatric disorders by inducing the
structure/function changes at synapses altering
neural transmission and blunting the growth of
the neuronal processes making connections in
key brain regions involved in learning and
memory –like hippocampus and prefrontal cor-
tex. Behavioral effects of stress-induced cortisol
Hormones and Behavior 19
are mediated by epigenetic changes at GR and
involve MAPK signaling pathway and Egr-1
(Revest et al. 2005). Another hormone,
melatonin –which is known for maintaining cir-
cadian rhythm –was also found implicated in
genesis of psychiatric disorders by various stud-
ies. Melatonin dysregulation perhaps plays by
disrupting molecular clock in SCN of the hypo-
thalamus and also the normal sleep pattern leading
to detrimental changes in structure/function of
hippocampus neurons, primarily suppressing con-
tinued neurogenesis which is crucial for learning
and memory.
A persistently low serum level and diminished
cortisol release response in acute stress challenge
links with anhedonia –feeling no pleasure in
normally pleasurable activities, depression, and
suicidal behavior. A cortisol release response
against presented acute stress challenge indicates
how fervent or disheartened individual would
respond to an eminent challenging situation. An
optimum cortisol challenge response seems nec-
essary for maintaining the healthy behavior.
Neuroplasticity induced by the hormones
set the basis for the further neuroplasticity in
future, a concept known as meta-neuroplasticity
(Salma 2014). A dysregulation of the meta-
neuroplasticity has been implicated in the progres-
sion of neurocognitive dysfunctions and also in
the genesis of many neuropsychiatric diseases in
adult where etiology has been developmental or
early-life stress (Lai and Huang 2011).
Cross-References
▶Hormones and Cognition
▶Hypothalamus
▶Passive Avoidance Learning
▶Rescue Behavior
▶Social Behavior
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