Effects of various inhibitors of phenylethanolamine N-methyltransferase on pulsatile release of LH in ovariectomized rats

Abstract

ABSTRACT This study was undertaken to investigate whether hypothalamic adrenaline is involved in pulsatile LH release in rats. Various inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme which catalyses the conversion of noradrenaline to adrenaline, were administered to freely moving ovariectomized rats bearing an atrial cannula. Blood samples were taken continuously from 09.00 to 11.00 h and from 14.30 to 17.00 h. The drugs were administered either at 11.00 h only or at both 11.00 and 14.00 h. The various treatments with the vehicle or an inhibitor of peripheral PNMT, SKF 29661, produced no decrease in any parameter of pulsatile LH release. A single injection of one of the central PNMT inhibitors, SKF 64139 or LY 134046, at 11.00 h had no effect on LH release, but when given at both times the drugs suppressed the mean LH level, pulse frequency and amplitude. The effect of these drugs on the level of dopamine, noradrenaline and adrenaline in the hypothalamus (including preoptic area) was assessed. There was no effect on the concentration of the catecholamines after SKF 29661. None of the treatments with SKF 64139 or LY 134046 resulted in a change in the level of dopamine or noradrenaline; the double dose did, however, produce a significantly greater depletion of adrenaline than that which was achieved with the single injection. These results suggest that the maintenance of normal LH pulses is dependent upon the presence of a sufficient level of hypothalamic adrenaline. The presence of at least 41% of the control level of hypothalamic adrenaline was compatible with the maintenance of LH pulses, but 30% or less of that level was insufficient for their normal occurrence. The effects of LY 134046 are particularly significant since this drug, unlike some of the other PNMT inhibitors, lacks α-adrenergic antagonist properties. J. Endocr. (1986) 111, 51–59