Control of Puberty by Excitatory Amino Acid Neurotransmitters and its Clinical Implications

Abstract

Excitatory amino acids, glutamate in particular, have a marked stimulatory effect on the reproductive axis, particulary at puberty. Glutamate, N-methyl-D-aspartate (NMDA), and kainite-stimulate gonadotropin-releasing hormone (GnRH) secretion in immature mammals and NMDA receptor stimulation results in precocious puberty in rats and monkeys. Puberty is characterized by an increased sensitivity of GnRH to glutamate as well as an increase in glutaminase activity in the hypothalamus. Glutamatergic and GABAergic regulation of GnRH secretion seem strongly interdependent around puberty. In addition to the transsynaptic glutamatergic regulation of GnRH secretion, a coordinated activity of glutamatergic neurons and astroglial cells has been shown to play an active role in puberty. The participation of kainate receptors in the estradiol-induced advancement of puberty suggest that these receptors may be involved in the estradiol-mediated activation of GnRH secretion at puberty. A case of precocious puberty associated with hyperglycinemia illustrates the NMDA involvement in puberty in humans. In this patient, the occurrence of precocious puberty was thought to result from excessive stimulation by glycine of the NMDA receptors linked to the GnRH neurons. Glutamate plays several roles in the hypothalamic mechanism of puberty as it has been shown in animal models, but there are still few clinical data supporting the role of glutamate in human puberty.

Social Opportunity Rapidly Regulates Expression of CRF and CRF Receptors in the Brain during Social Ascent of a Teleost Fish, Astatotilapia burtoni

“…Onset of puberty in mammals is generally characterized by an increase in GnRH1 secretion and concurrent FSH and LH release, which leads to gonadal maturation and appearance of secondary sex characteristics arising from production of sex-steroids [67], [68]. This process results from the activation of the GnRH1 pulse generator, stimulated by functional changes occurring in neuronal and astroglial networks connected to hypothalamic neurons [69]. The primary mode of excitation in the hypothalamus is via glutamate release [70], and GnRH1 neurons receive direct glutamatergic innervation [71].…”

PRECLINICAL STUDY: Age‐dependent differences in sensitivity and sensitization to cannabinoids and ‘club drugs’ in male adolescent and adult rats

“…For example, male rats that received subchronic phencyclidine twice daily for 7 days beginning at PN42 exhibited decreased locomotion, disturbed social behavior, and increased number of errors in a spatial learning task when tested as adults (>PN70) (Schwabe, Klein & Koch 2006). In addition, glutamate has been shown to be involved in timing of puberty (Parent, Matagne & Bourguignon 2005), raising the possibility that subchronic blockade at NMDA receptors may affect this hallmark of adolescent development.…”

Selective role of neuropeptide Y receptor subtype Y2 in the control of gonadotropin secretion in the rat

“…Our results demonstrate an inhibitory effect of PYY on GnRH release, which is coincident with data reported previously by our group (14,40) on the ability of PYY to decrease hypothalamic GnRH secretion in prepubertal and adult male rats, thus suggesting the involvement of Y 2 receptor activation in mediating such action. The inhibition of GnRH release might be directly exerted on GnRH neurons or mediated through blockade of different neurotransmitters such as glutamate, NPY, or noradrenaline, which are well-known stimulatory inputs for GnRH neurons (23,25,29,35,36,46) and whose release is inhibited after activation of Y 2 receptors (9,11,27,30). Admittedly, the mechanism(s) involved in the reduction of GnRH release by PYY needs to be characterized further.…”