Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptorsin the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

Excitatory amino acids, such as glutamate, constitute a major transmitter s ystem in the control of hypothalamic-pituitary secretion. Different subtype s of glutamate receptors, such as NMDA (N-methyl-D-aspartic acid) and KA (k ainate) receptors, are involved in the control of anterior pituitary secret ion. Other receptor subtypes, such as AMPA (activated by alpha-amino-3-hydr oxy-5-methylisoxazole-4-propionic acid) and metabotropic receptors, have be en identified, although their role in the control of neuroendocrine functio n remains largely unknown. Recent reports have demonstrated the involvement of AMPA receptors in the control of the steroid-induced luteinizing hormon e (LH) surge in female and growth hormone (GH) secretion in male rats. The aim of this study was to assess the potential role of AMPA receptors in the control of GH, prolactin (PRL) LH and follicle-stimulating hormone (FSH) s ecretion in prepubertal 23-day-old rats. To this end, prepubertal female ra ts were injected with AMPA (2.5 or 5 mg/kg i.p.) or the antagonist of AMPA receptors 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo (f) quinoxaline-7-sulf onamide (NBQX; 0.25 or 0.50 mg/kg i.p.). Serum LH and FSH concentrations an d hypothalamic LH-releasing hormone (LHRH) content remained unchanged after AMPA or NBQX administration. In contrast, serum PRL, levels significantly decreased 15, 30 and 60 min after i.p. administration of AMPA and increased 120 min after NBQX treatment, whereas serum GH levels increased after AMPA treatment and decreased after NBQX administration. Considering that AMPA h as been shown to activate a subset of kainate receptors, its effects were c ompared with those elicited by 2.5 mg/kg KA in prepubertal female rats. At this age, however, KA was unable to reproduce the effects of AMPA on PRL, a nd GH secretion, thus suggesting that the actions observed after AMPA admin istration were carried out specifically through AMPA receptors. In addition , as the effects of AMPA on LH secretion in adult females have been proved to be steroid-dependent, the effects of AMPA (2.5 mg/kg) and NBQX (0.5 mg/k g) were tested in prepubertal animals with different gonadal backgrounds, i .e. intact males, and intact and ovariectomized (OVX) females. The effects of AMPA in prepubertal females appeared to be modulated by ovarian secretio n, as the inhibition of PRL secretion disappeared and LH secretion was part ially suppressed by AMPA in OVX animals whereas the stimulatory effect on G H release was enhanced by ovariectomy. Furthermore, in male rats, AMPA admi nistration significantly decreased PRL secretion and increased serum GH lev els, the amplitude of the GH response being higher than in prepubertal fema les. To ascertain the pituitary component for the reported actions of AMPA, hemi-pituitaries of male rats were incubated in the presence of AMPA (10(- 8)-10(-6) M). The results obtained showed no effect of AMPA on PRL, GH and gonadotropin secretion in vitro. Finally, we investigated the involvement o f the dopaminergic (DA) system in the inhibitory action of AMPA on PRL secr etion. Pre-treatment of prepubertal female rats with a dopamine receptor an tagonist (domperidone: 1 mg/kg ) resulted in the blockage of AMPA-mediated inhibition of PRL secretion, thus suggesting that this action is probably m ediated by an increase in DA activity. In conclusion, we provide evidence f or the physiological role of AMPA receptors in the control of PRL and GH se cretion in prepubertal rats. In contrast, our data cast doubts on the invol vement of AMPA receptors in the regulation of gonadotropin secretion at thi s age. The effects of AMPA reported herein were not mediated through activation of kainate receptors and were probably exerted at the hypothalamic or suprahy pothalamic levels. In addition, we show that ovarian secretion actively mod ulates the effects of AMPA receptor activation on anterior pituitary secret ion in prepubertal female rats.