PERIPUBERTAL CHANGES IN THE NATURE OF THE GNRH RESPONSE TO ALPHA-ADRENOCEPTOR STIMULATION INVITRO AND THEIR MODULATION BY TESTOSTERONE

Adrenergic mechanisms have been widely implicated in the regulation of GnRH secretion in adult rats but their role in young animals, in which the activity of the GnRH neurones is minimal, is unclear. These experiments were done to examine the effects of α-adrenoceptor stimulation on the secretion in vitro of GnRH by hypothalami from immature and adult male rats. α1-adrenoceptor agonist, phenylephrine (10-9-10-7M), stimulated release of GnRH from hypothalami from adult (200 g) and peripubertal (150 g) rats but inhibited markedly the secretion of the releasing factor from the limited stores available in hypothalami from immature (50 or 100 g) rats. The stimulatory and inhibitory responses to phenylephrine, evident in adult and younger rats respectively, were concentration-dependent and antagonized readily by the selective α1-adrenoceptor antagonist, alfuzosin (10-6M), but not by the β-adrenoceptor antagonist, propranolol (10-6M). Hypothalami from 14-day castrated adult rats, in which the serum LH was elevated and hypothalamic GnRH content reduced, responded to α1-adrenoceptor stimulation in vitro, like those from immature rats, with a marked reduction in GnRH release. In contrast, hypothalami from corresponding castrates bearing testosterone implants, which maintained the hypothalamic GnRH content and serum LH and testosterone concentrations at levels similar to those of intact controls, exhibited the normal ‘adult’ response to phenylephrine. Studies utilizing3H-prazosin indicated that the number (Bmax) of hypothalamic α1-adrenoceptor binding sites increases at puberty but that receptor affinity (KD) is unchanged. A significant increase in β-adrenoceptor binding sites was also apparent in the adult but the density of α2-adrenoceptors was unchanged. The data accentuate the importance of adrenergic mechanisms in the regulation of GnRH secretion and raise the possibility that alterations in the nature of the GnRH response to α1-adrenoceptor stimulation may be a contributory factor in the initiation of puberty. © 1990 S. Karger AG, Basel.