Noradrenaline and prostaglandin E2 stimulate LH-RH release from rat median eminence through distinct 1-alpha-adrenergic and PGE2 receptors.

Abstract

Noradrenaline (NA) and prostaglandin (PG) E2 produced a dose-related stimulation of luteinizing hormone releasing hormone (LH-RH) release from incubated median eminence of adult male rats, with ED50 values of 6.10(-7) and 8.10(-8) M, respectively. The effects of some adrenoceptor agonists (10(-5) M) on LH-RH release were tested: only phenylephrine (alpha 1-agonist) stimulated LH-RH release; clonidine (alpha 2 greater than alpha 1-agonist) and isoproterenol (beta-agonist) were ineffective. Adrenoceptor antagonists (10(-6) M) were also tested: prazosin (alpha 1-antagonist) and phentolamine (alpha 1/alpha 2-antagonist) almost completely suppressed the enhanced release of LH-RH induced by NA. In contrast, neither yohimbine (alpha 2-antagonist) nor propranolol (beta-antagonist) altered this effect of NA. When tested alone, no significant effect was obtained on basal LH-RH release with any of the antagonists tested. Moreover, at concentrations that blocked the stimulation produced by NA, the adrenoceptor antagonists did not alter the effect of PGE2. Among seven PGs tested at 10(-6) M, only PGE2, PGE1, PGA2, and 16,16-dimethyl PGE2 significantly enhanced LH-RH secretion. 8-iso PGE2 weakly stimulated LH-RH secretion, whereas PGF2 alpha and PGD2 were ineffective. A direct correlation existed between the potency of these compounds to modify LH-RH secretion and to inhibit specific [3H]-PGE2 binding to hypothalamic membranes. In conclusion, these results suggest that the stimulation of LH-RH from median eminence induced by NA and PGE2 involves the activation of an alpha 1-adrenergic receptor and a PGE2 receptor, respectively.