Control of Pulsatile Secretion of Gonadotrophin Releasing Hormone from Hypothalamic Explants

We have studied the secretion of gonadotrophin releasing hormone (GnRH) from hypothalamic explants of male rats at different ages in an attempt to delineate the neuroendocrine mechanism of the onset of puberty. In this paper, we review some of our recent studies and we provide evidence of a dual control played by receptors to neuroexcitatory amino acids. We showed previously that isolated explants of rat hypothalamus could secrete GnRH in a pulsatile manner. The onset of puberty was characterized by a 2-fold increase in frequency of GnRH secretory pulses. This reduction of the interval between GnRH pulses involved an inhibitory autofeedback effect of GnRH on the pulse generator which was shut off following a secretory episode. This period of refractoriness was longer before puberty than after the onset of puberty. Activation of receptors to neuroexcitatory amino acids (N-methyl-D-aspartate; NMDA-type) was involved in the mechanism of pulsatile GnRH secretion. Striking developmental changes in NMDA-receptor-mediated GnRH secretion were demonstrated with a maximal activity around the time of the onset of puberty. Similar changes occurred in orchidectomized animals, indicating that this maturational process was gonad-independent. While evidence accumulated that NMDA receptors were involved in a stimulatory control of GnRH secretion, we found that NMDA receptors mediated an inhibitory effect on GnRH secretion. This inhibitory effect was very potent in the immature hypothalamus and it showed a marked reduction in potency before onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS