Stephen Marc Breedlove

Stephen Marc Breedlove
Michigan State University | MSU · Department of Neuroscience

Ph.D.

About

223
Publications
91,327
Reads
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13,374
Citations
Additional affiliations
January 2010 - present
January 2010 - present
Pennsylvania State University
January 2008 - December 2009
Kyoto Prefectural University of Medicine
Education
January 1978 - September 1982
September 1976 - December 1978
September 1972 - December 1975
Yale University
Field of study
  • Psychology

Publications

Publications (223)
Article
In laboratory animals, exposure to gonadal steroid hormones before and immediately after birth can exert permanent effects on many behaviors, particularly reproductive behaviors. The extent to which such effects occur in humans remains an open question, but several lines of evidence indicate that perinatal levels of both androgens and estrogens may...
Article
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Individual variation in the age of pubertal onset is linked to physical and mental health, yet the factors underlying this variation are poorly understood. Life history theory predicts that individuals at higher risk of mortality due to extrinsic causes such as infectious disease should sexually mature and reproduce earlier, whereas those at lower...
Article
Ovarian estrogens may influence the development of the human brain and behavior, but there are few opportunities to test this possibility. Isolated GnRH deficiency (IGD) is a rare endocrine disorder that could provide evidence for the role of estrogens in organizing sexually differentiated phenotypes: Unlike typical development, development in indi...
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Primate same-sex sexual behavior (SSSB) is rarely observed in strepsirrhine species, and only somewhat more common in platyrrhines, but is observed in nearly all catarrhine species, including humans, suggesting the common catarrhine ancestor as the origin of routine SSSB. In mice, disruption of the transient receptor potential cation channel 2 (TRP...
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Low perinatal androgens predict recalled childhood gender nonconformity in men Abstract The contributions of gonadal hormones to the development of human behavioral sex differences are subjects of intense scientific and social interest. Isolated GnRH deficiency (IGD) is a rare endocrine disorder that can reveal a possible role of early gonadal horm...
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Among non-human mammals, exposure to androgens during critical periods of development leads to gynephilia (attraction to females), whereas the absence or low levels of prenatal androgens leads to androphilia (attraction to males). However, in humans, retrospective markers of prenatal androgens have only been associated with gynephilia among women,...
Article
Testosterone (T) exerts anxiolytic effects through functional androgen receptors (ARs) in rodents. T treatment of castrated mice reduces anxiety-like behavior in wild-type (WT) males, but not males with a spontaneous mutation that renders AR dysfunctional (testicular feminization mutation, Tfm). Using Cre-LoxP technology we created males carrying i...
Preprint
The contributions of gender socialization and direct hormonal action on the brain in the development of human behavioral sex differences are subjects of intense scientific and social interest. Prior research indicates masculinized behavioral patterns in individuals with high prenatal androgen exposure raised as girls, but complementary evidence reg...
Article
Circulating gonadal hormones have been linked to variation in the structure and function of the adult human brain, raising the question of how cognition is affected by sex hormones in adulthood. The impacts of progestogens and estrogens are of special interest due to the widespread use of hormone supplementation. Multiple studies have analyzed rela...
Article
Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the puber...
Article
Key points: Muscle-derived neurotrophic factors may offer therapeutic promise for treating neuromuscular diseases. We report that a muscle-derived neurotrophic factor, BDNF, rescues synaptic and muscle function in a muscle-type specific manner in mice modelling Kennedy's disease (KD) We also find that BDNF rescues select molecular mechanisms in sl...
Article
Experiments in male rodents demonstrate that sensitivity to the organizational effects of steroid hormones decreases across the pubertal window, with earlier androgen exposure leading to greater masculinization of the brain and behavior. Similarly, some research suggests the timing of peripubertal exposure to sex steroids influences aspects of huma...
Article
On average, the length of the index finger (digit 2) divided by the length of the ring finger (digit 4) on the right hand, is greater in women than in men. Converging evidence makes it clear that prenatal androgens affect the development of digit ratios in humans and so are likely responsible for this sex difference. Thus, differences in 2D:4D betw...
Article
Relatively little is known about the effects of endogenous and exogenous steroid hormones on ecologically relevant behavioral and cognitive phenotypes in women, such as emotion recognition, despite the widespread use of steroid hormone-altering hormonal contraceptives (HCs). Though some previous studies have examined the effect of HC use, estradiol...
Article
Oxytocin (OT) often regulates social behaviors in sex-specific ways, and this may be due to sex differences in the brain OT system. Adult male rats show higher OT receptor (OTR) binding in the posterior bed nucleus of the stria terminalis (pBNST) than adult female rats. Here, we investigated the mechanisms that lead to this sex difference. First, w...
Article
Full-text available
Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing genes to reg...
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Background: Post-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex...
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Background Our previous study revealed that adult female rats respond differently to trauma than adult males, recapitulating sex differences in symptoms of post-traumatic stress disorder (PTSD) exhibited by women and men. Here, we asked two questions: does the female phenotype depend on (1) social housing condition and/or (2) circulating gonadal ho...
Research
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For over 50 million years, every single mammal on Earth had to enter the world through a harrowing passage: the birth canal. The hazards of this journey, short in distance but potentially prolonged in duration, may have peaked in our own species, where the evolution of larger and larger brains at birth seems to have been limited by increasing risks...
Article
A distinguishing aspect of spinal bulbar muscular atrophy (SBMA) is its androgen-dependence, possibly explaining why only males are clinically affected. This disease, which impairs neuromuscular function, is linked to a polyglutamine expansion mutation in the androgen receptor (AR). In mouse models of SBMA, motor dysfunction is associated with pron...
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In non-human vertebrate species, sexual differentiation of the brain is primarily driven by androgens such as testosterone organizing the brains of males in a masculine fashion early in life, while the lower levels of androgen in developing females organize their brains in a feminine fashion. These principles may be relevant to the development of s...
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Research
Faint heart never won fair lady. Thomas Lodge, Rosalind Across most mammalian species, males must first compete with one another, sometimes violently, before having the opportunity to mate with a female. These two encounters— an aggressive interaction with one or more males followed by mating with a female—sometimes take place within minutes of eac...
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Ongoing political controversies around the world exemplify a long-standing and widespread preoccupation with the acceptability of homosexuality. Nonheterosexual people have seen dramatic surges both in their rights and in positive public opinion in many Western countries. In contrast, in much of Africa, the Middle East, the Caribbean, Oceania, and...
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Spinal bulbar muscular atrophy (SBMA) is a progressive, late onset neuromuscular disease causing motor dysfunction in men. While the morphology of the neuromuscular junction (NMJ) is typically affected in neuromuscular disease, whether the NMJs in SBMA are similarly affected by disease is not known. Such information will shed light on whether defec...
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Defects in axonal transport are seen in motoneuronal diseases, but how that impairment comes about is not well understood. In spinal bulbar muscular atrophy (SBMA), a disorder linked to a CAG/polyglutamine repeat expansion in the androgen receptor (AR) gene, the disease-causing AR disrupts axonal transport by acting in both a cell-autonomous fashio...
Article
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Unlabelled: Spinal and bulbar muscular atrophy (SBMA) in men is an androgen-dependent neuromuscular disease caused by expanded CAG repeats in the androgen receptor (AR). Whether muscle or motor neuron dysfunction or both underlies motor impairment in SBMA is unknown. Muscles of SBMA mice show significant contractile dysfunction, implicating them a...
Article
The posterodorsal aspect of the medial amygdala (MePD) in rats is sexually dimorphic, being larger and containing more and larger neurons in males than in females. It is also highly lateralized, with the right MePD larger than the left in both sexes, but with the smaller left MePD actually containing more and larger neurons than the larger right. A...
Chapter
Sex differences in the brain impact physiology as well as behavior. The most important factors causing sex differences are the programming effects of gonadal hormones during critical periods in development and the acute effects of hormones later in life. Ultimately, however, differences in gonadal hormones depend on differences in sex chromosomes,...
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Full-text available
We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous...
Article
Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived ne...
Article
Full-text available
Spinal and bulbar muscular atrophy (SBMA) is characterized by progressive muscle weakness linked to a polyglutamine expansion in the androgen receptor (AR). Current evidence indicates that mutant AR causes SBMA by acting in muscle to perturb its function. However, information about how muscle function is impaired is scant. One fundamental question...
Article
Prenatal testosterone exposure may be protective against disordered eating. However, prior studies have produced mixed results. Developmental differences in prenatal testosterone's protective effects on disordered eating may explain these discrepancies. Indeed, studies have differed in the age of participants assessed, with data supporting prenatal...
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Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and de...
Article
Full-text available
Spinal and bulbar muscular atrophy (SBMA) is a late onset, progressive neurodegenerative disease linked to a polyglutamine (polyQ) expansion in the androgen receptor (AR). Men affected by SBMA show marked muscle weakness and atrophy, typically emerging mid-life. Given the androgen-dependent nature of this disease, one might expect AR antagonists to...
Article
Men are less likely than women to suffer from anxiety disorders. Because gonadal hormones play a crucial role in many behavioral sex differences, they may underlie sex differences in human anxiety. In rodents, testosterone (T) exerts anxiolytic effects via the androgen receptor (AR): we found that male mice with a naturally-occurring mutation rende...
Article
Astrocytes in the posterodorsal portion of the medial amygdala (MePD) are sexually dimorphic in adult rats: males have more astrocytes in the right MePD and more elaborate processes in the left MePD than do females. Functional androgen receptors (ARs) are required for masculinization of MePD astrocytes, as these measures are demasculinized in adult...
Article
Introduction: Testosterone (T) induces motor dysfunction in transgenic (Tg) mice that overexpress wild-type androgen receptor (AR) in skeletal muscles. Because many genes implicated in motor neuron disease are expressed in skeletal muscle, mutant proteins may act in muscle to cause dysfunction in motor neuron disease. Methods: We examined contra...
Article
Research suggests that prenatal testosterone exposure may masculinize (i.e., lower) disordered eating (DE) attitudes and behaviors and influence the lower prevalence of eating disorders in males versus females. How or when these effects become prominent remains unknown, although puberty may be a critical developmental period. In animals, the mascul...
Article
Gonadal androgens are critical for the development and maintenance of sexually dimorphic regions of the male nervous system, which is critical for male-specific behavior and physiological functioning. In rodents, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) provide a useful example of a neural system dependent on androgen. Unl...
Article
The posterodorsal medial amygdala (MePD) exhibits numerous sex differences including differences in volume and in the number and morphology of neurons and astroctyes. In adulthood, gonadal hormones, including both androgens and estrogens, have been shown to play a role in maintaining the masculine character of many of these sex differences, but whe...
Article
The spinal nucleus of the bulbocavernosus (SNB) in rodents is a neuromuscular system consisting of lumbar motoneurons and the perineal muscles they innervate, the bulbocavernosus and levator ani. This system is present prenatally in both males and females but degenerates postnatally in females because of the lack of perinatal androgens. Whether and...
Article
Full-text available
Spinal and bulbar muscular atrophy (SBMA) impairs motor function in men and is linked to a CAG repeat mutation in the androgen receptor (AR) gene. Defects in motoneuronal retrograde axonal transport may critically mediate motor dysfunction in SBMA, but the site(s) where AR disrupts transport is unknown. We find deficits in retrograde labeling of sp...
Article
Testosterone influences the hypothalamic-pituitary-adrenal axis, anxiety-related behavior, and sensorimotor gating in rodents, but little is known about the role of the androgen receptor (AR) in mediating these influences. We compared levels of the stress hormone corticosterone at baseline and following exposure to a novel object in an open field i...
Article
Many men suffering from stress, including post-traumatic stress disorder (PTSD), report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP) system in the lumbar spinal cord that is a primary mediator for male reproductive functions. To ask whether acute severe st...
Article
Full-text available
Perinatal exposure to testosterone (T), which can act upon both the androgen receptor (AR) and, via aromatization of T into estrogens, upon estrogen receptors, organizes many adult behaviors in rodents. We compared behaviors in wild-type (WT) male rats and AR-deficient rats with the testicular feminization mutation (Tfm), which on the day of birth...
Article
Full-text available
Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is...
Article
Castration of adult male rats causes dendrites of the spinal nucleus of the bulbocavernosus (SNB) to retract. The neurotrophin brain-derived neurotrophic factor (BDNF) is implicated in mediating these androgenic effects on SNB dendrites. We previously found that castration decreases BDNF mRNA in SNB somata and BDNF protein in proximal SNB dendrites...
Article
Full-text available
There is now compelling evidence that the ratio of the length of the second digit divided by the length of the fourth digit (2D:4D) is affected by prenatal androgens in humans. This ratio is greater in females than males from fetal life through adulthood, correlates with polymorphism in the androgen receptor gene in men, is feminine in XY androgen...
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Full-text available
Mark R. Rosenzweig, emeritus professor of psychology at the University of California, Berkeley, died on July 20, 2009, shortly before his 87th birthday. Born in Rochester, New York, on September 12, 1922, the son of a lawyer and a homemaker mother, Rosenzweig entered the University of Rochester in 1940, where he first encountered his lifelong profe...
Article
A(11) diencephalospinal dopamine (DA) neurons provide the major source of DA innervation to the spinal cord. DA in the dorsal and ventral horns modulates sensory, motor, nociceptive, and sexual functions. Previous studies from our laboratory revealed a sex difference in the density of DA innervation in the lumbar spinal cord. The purpose of this st...
Article
The courtship behavior of animals has often been likened to a dance, each partner alternating with the other to produce a seamless and pleasing whole. Indeed, dancing has proven to be an important prelude to a future union for many human pairs. In this issue of Neuron, we learn that even within a sex an elaborate, highly coordinated dance between f...
Article
The amygdala has received considerable attention because of its established role in specific behaviors and disorders such as anxiety, depression, and autism. Studies have revealed that the amygdala is a complex and dynamic brain region that is highly connected with other areas of the brain. Previous works have focused on neurons, demonstrating that...