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 (10^⁵M) on LH-RH release were tested: only phenyleph-rine (α₁-agonist) stimulated LH-RH release; clonidine (α₂ > α₁-agonist) and isoproterenol (β-agonist) were ineffective. Adrenoceptor antagonists (10^⁶M) were also tested: prazosin (α₁-antagonist) and phentolamine (α₁/α₂-antagonist) almost completely suppressed the enhanced release of LH-RH induced by NA. In contrast, neither yohimbine (α₂-antagonist) nor propranolol (β-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 10^⁶M, only PGE₂, PGE₁, PGA₂, and 16,16-dimethyl PGE₂ significantly enhanced LH-RH secretion. 8-iso PGE₂ weakly stimulated LH-RH secretion, whereas PGF_2α and PGD₂ were ineffective. A direct correlation existed between the potency of these compounds to modify LH-RH secretion and to inhibit specific [³Hs]-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 α₁-adrenergic receptor and a PGE2 receptor, respectively.