Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle. Gonadotropin-Releasing Hormone, Glutamate, and GABA

Institute for Neuroscience, University of Texas, Austin, Texas 78712, USA.
International review of cell and molecular biology (Impact Factor: 3.42). 02/2009; 274:69-127. DOI: 10.1016/S1937-6448(08)02002-9
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The hypothalamic-pituitary-gonadal (HPG) axis undergoes a number of changes throughout the reproductive life cycle that are responsible for the development, puberty, adulthood, and senescence of reproductive systems. This natural progression is dictated by the neural network controlling the hypothalamus including the cells that synthesize and release gonadotropin-releasing hormone (GnRH) and their regulatory neurotransmitters. Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters in the central nervous system, and as such contribute a great deal to modulating this axis throughout the lifetime via their actions on receptors in the hypothalamus, both directly on GnRH neurons as well as indirectly through other hypothalamic neural networks. Interactions among GnRH neurons, glutamate, and GABA, including the regulation of GnRH gene and protein expression, hormone release, and modulation by estrogen, are critical to age-appropriate changes in reproductive function. Here, we present evidence for the modulation of GnRH neurosecretory cells by the balance of glutamate and GABA in the hypothalamus, and the functional consequences of these interactions on reproductive physiology across the life cycle.

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    • "The activity and functionality of this neuronal circuitry is controlled through different neurotransmitters; activation of the complex KiSS-1/kisspeptin/GPR54 system and increased glutamatergic neurotransmission are two excitatory events stimulating the onset of puberty (Maffuci and Gore, 2009; Perfito and Bentley, 2009; Meza-Herrera et al., 2010; Meza-Herrera, 2012; Meza-Herrera and Tena-Sempere, 2012). Besides to its role as the main neurotransmitter within the CNS, glutamate has also been involved in the modulation of metabolic activity, gene expression and protein synthesis (Parent et al., 2005; Meza-Herrera, 2008, 2012; Maffuci and Gore, 2009). However, reactivation of GnRH neurons at puberty not only involves changes in the expression of defined hormones or neurotransmitters (Meza-Herrera, 2008, 2012), but also can be modulated by the concentration of endogenous metabolites (Blache et al., 2006). "
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    ABSTRACT: Different neurotransmitter and neuromodulatory systems regulate synthesis and secretion of GnRH. Whereas the endocrine and neural systems are activated in response to the metabolic status and the circulating levels of specific blood metabolites, glutamate receptors have been reported at hepatic level. This study evaluated the possible effect of glutamate supplementation upon changes in serum concentrations across time for total protein (TP), urea (UR) and cholesterol (CL) around the onset of puberty in goats. Prepuberal female goats (n=18) were randomly assigned to: (1) excitatory amino acids group, GLUT, n=10; 16.52±1.04kg live weight (LW), 3.4±0.12 body condition score (BCS) receiving an i.v. infusion of 7mgkg(-1) LW of l-glutamate, and (2) Control group, CONT, n=8; 16.1±1.04kg LW, 3.1±0.12 BCS. General averages for LW (23.2±0.72kg), BCS (3.37±0.10 units), serum TP (65.28±2.46mgdL(-1)), UR (23.42±0.95mgdL(-1)), CL (77.89±1.10mgdL(-1)) as well as the serum levels for TP and UR across time did not differ (P>0.05) between treatments. However, while GLUT positively affected (P<0.05) both the onset (207±9 vs. 225±12 d) and the percentage (70 vs. 25%) of females showing puberty, a treatment×time interaction effect (P<0.05) was observed in the GLUT group, with increases in serum cholesterol, coincident with the onset of puberty. Therefore, in peripuberal glutamate supplemented goats, serum cholesterol profile could act as a metabolic modulator for the establishment of puberty, denoting also a potential role of glutamate as modulator of lipid metabolism.
    Animal Reproduction Science 04/2014; DOI:10.1016/j.anireprosci.2014.04.004 · 1.51 Impact Factor
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    • "The activity and functionality of this neuronal circuitry is, in turn, controlled through different neurotransmitters and metabolic hormones. Whereas activation of the complex KiSS-1/kisspeptin/GPR54 system augments the glutamatergic neurotransmission, increases in the metabolic status and in the adipocyte-derived hormone leptin are excitatory events, stimulating not only the onset of puberty but also the reproductive cyclicity in adult stages (Maffucci and Gore, 2009; Meza-Herrera et al., 2010; Meza- Herrera, 2012; Meza-Herrera and Tena-Sempere, 2012). "
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    ABSTRACT: Abstract The effect of betacarotene (BC) supplementation on serum triiodothyronine (T3) levels over time in prepubertal goats was evaluated. Goats (n = 17; 3 months old; 7/8 Saanen-Alpine; 26° NL) were randomly assigned to one of the following two groups: 1) the betacarotene group, supplemented daily with 50 mg of BC (n = 9; live weight [LW]: 17.3 ± 1.0 kg; body condition score [BCS]: 3.34 ± 0.12), or 2) the control group (CC; n = 8; LW:16.1 ± 1.0 kg; BCS = 3.17 ± 0.12). The initial mean LW (16.7 ± 1.0 kg) and BCS (3.31 ± 0.12) were similar (p > 0.05) in both groups. Whereas BC supplementation did not affect the onset of puberty (215.7 vs. 226.7 ± 6.6 days; p > 0.05) for the BC and CC, respectively, increases in serum T3 during the second half of the experiment were observed in the BC supplementation group (p < 0.05). As the LW and serum T3 levels increased, the natural photoperiod decreased, revealing a negative correlation (p < 0.05) between the variables; the observed values were r = - 0.94 for LW and photoperiod and r = - 0.41 for T3 and photoperiod. Long-term BC supplementation was not associated with a precocious onset or an increased percentage of goats reaching puberty. Long-term BC supplementation positively affected the release pattern of triiodothyronine over time, suggesting a potential role of BC as a thyroid-activating molecule; these results might possess clinical significance. Additional keywords: Goats, betacarotene, puberty, progesterone, triiodothyronine.
    Small Ruminant Research 02/2014; 116:176-182. DOI:10.1016/j.smallrumres.2013.10.017 · 1.13 Impact Factor
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    • "In addition, the investigation of the toxic potential of a substance upon the reproductive system must include the dosage of serum levels of hormones involved in the homeostasis of the hypothalamic axis, hypophysis, and gonads [1]. First, the hypothalamus produces and secretes the GnRH which stimulates the hypophysis to release the FSH and LH; these, in turn, have a direct action upon the ovaries promoting follicular development and release of the oocyte [34]. "
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    ABSTRACT: The treatment during the embryonic preimplantation phase of Wistar rats with the Pradosia huberi extract did not interfere with the water and feed consumption, as well as upon the body-weight gain. However, it has expressed a decrease of the uterine implant number, followed by the preimplantation losses at all applied doses (1.22, 6.1, and 30.5 mg/kg), and the number of embryonic resorptions in the two highest doses (6.1 and 30.5 mg/kg). After the organ weighing (hypophysis, ovaries, and uterus), only the relative weight of the hypophysis was raised at the different doses (1.22, 6.1, and 30.5 mg/kg). It was concluded that the hydroalcoholic extract of Pradosia huberi compromises the reproductive ability during the embryonic preimplantation phase, suggesting a possible toxic effect upon the reproductive system of Wistar rats.
    03/2013; 2013:294172. DOI:10.1155/2013/294172
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