Effect of Ovarian Hormones on the Hypothalamic Excitatory Amino Acids System during Sexual Maturation in Female Rats

Abstract

The present experiments were designed to study in female rats during sexual maturation: (1) the hypothalamic release of aspartate (Asp), glutamate (Glu) and glycine (Gly) which are the excitatory amino acids (EAAs) involved in NMDA neurotransmission and of taurine (Tau), a putative inhibitory amino acid of GnRH secretion; (2) the relationships between the effect of estrogen-progesterone (EP) on the release of these EAAs and the secretion of gonado-tropins, and (3) the effect of hypothalamic NMDA receptor stimulation on EAAs release by the hypothalamus as well as the effect of EP on this release. The release of EAAs by the anterior preoptic and medial-basal hypothalamic areas (APOA-MBH) is significantly higher in peripubertal than in prepubertal rats (p < 0.01). EP treatment in prepubertal rats (16 days of age) decreased LH and FSH plasmatic levels and also the in vitro release of Asp, Glu, Gly and Tau. Contrary to the observations in prepubertal rats, in 30-day-old peripubertal rats the ovarian hormones significantly (p < 0.01) increased the levels of LH and FSH as well as the release to the medium of these amino acids. In prepubertal rats, the addition of NMDA to the incubation media significantly increased the release of Asp and of Glu. The NMDA receptor agonist did not modify the hypothalamic release of Gly and Tau to the incubation media. On the other hand, pretreatment with EP did not modify either the Asp and Glu release response to NMDA or the lack of response on Gly and Tau. In peripubertal rats NMDA also significantly increased the in vitro release of Asp and Glu, but at this age pretreatment with EP significantly potentiated the release of these amino acids induced by NMDA. On the other hand, the ovarian hormones induced Gly and Tau release by NMDA, this not being observed in control rats. In conclusion, the present results indicate that during sexual maturation the in vitro release of Asp, Glu and Gly by APOA-MBH increases and Tau release decreases. EP pretreatment of prepubertal rats decreases the hypothalamic release of EAAs as well as the serum LH and FSH levels but increases both EAAs release and plasmatic gonadotropin in peripubertal rats. On the basis of these results it is proposed that the increase in EAAs release by the hypothalamus is directly connected with the onset of puberty and that the maturation of the positive feedback effect of ovarian hormones on gonadotropin secretion is related to the maturation of the capacity of EP to increase hypothalamic EAAs. Before this maturational event EP inhibits EAAs release as well as gonadotropin release (prepubertal rats). NMDA receptor stimulation leads to a positive mechanism which increases the release of Asp and Glu from APOA-MBH both in prepubertal and peripubertal rats, but EP potentiates this mechanism only in peripubertal rats. This could be an additional neuroendocrine mechanism involved in the increase of gonadotropin during sexual maturation which induces the onset of puberty and the preovulatory discharge of these pituitary hormones.

Chapter 2 Hypothalamic Neural Systems Controlling the Female Reproductive Life Cycle

“…Thus, beyond apparent changes to glutamate receptors themselves, there are accompanying changes in glutamate availability throughout the life cycle and it appears that these levels are regulated, at least in part, by the steroid hormone environment (Carbone et al , 1995; Jarry et al , 1992). …”

MK-801 infusions to the ventral tegmental area and ventromedial hypothalamus produce opposite effects on lordosis of hormone-primed rats

“…As well, progestins can rapidly alter NMDAR function by increasing or decreasing NMDA-activated calcium influx and blocking progesterone's metabolism to 3α,5α-THP attenuates this effect (Gibbs et al, 1999;Smith, 1991). Progestins also indirectly alter NMDAR function in the hypothalamus and preoptic area by modulating the release of glutamate (Carbone et al, 1995;Fleischmann et al, 1990). Third, progesterone's actions at NMDARs in some areas of the brain can lead to functional changes.…”

Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions

“…Stimulatory effects of NMDA have been reported in adult female rats (6, 7), whereas both stimulatory (8) and inhibitory actions (9) have been described in prepubertal animals. It has been proposed that the effects of NMDA on PRL depend on the previous circulating concentrations of the hormone, with a conversion of the PRL response from stimulation in cyclic females to inhibition during lactation (10,11).…”