Monoamines and Ovulation in the Rat

Abstract

A study has been made of the possible involvement of monoaminergic pathways in the neural mechanisms which activate the adenohypophysis to release ovulating hormone. Practically no animals ovulated after treatment with reserpine (5 mg/kg sc), and a 1 mg/kg dose inhibited ovulation in 50%. In agreement with earlier data, blockade of ovulation occurred only when reserpine was administered prior to the assumed critical period of LH release and not if the injection was given immediately afterward. The inhibitory effect of reserpine on ovulation was prevented by treatment with either of the monoamine oxidase inhibitors, pargyline (25 mg /kg sc) or nialamide (200 mg/kg sc). However, experiments involving treatment with nialamide or nialamide-DOPA on the morning of proestrus, combined with hypophysectomy at different times during the critical period for LH discharge, revealed that increased monoamine levels did not advance the time of LH release. Pargyline itself, at a dosage of 50 mg/kg sc, blocked ovulation, and on the day following treatment uterine weights were increased over controls. Both effects were obtained only if the compound was given before the critical period and not when administered immediately afterward. Blocking dosages of reserpine, however, did not effect increases in uterine weight. Experiments with pargyline in combination with the monoamine precursors DOPA and 5-HTP indicate that the effects of pargyline on ovulation and uterine weight are not brought about by increased monoamine levels even though intact monoaminergic pathways appear to be necessary for triggering the ovulatory discharge of LH. (Endocrinology 83: 170, 1968) F studies on pharmacological blockade of ovulation, data have accumulated suggesting that both cholinergic and monoaminergic mechanisms may be involved in the activation of the adenohypophysis to release ovulating hormone (13) A significant role of central nervous monoaminergic pathways in controlling the ovulatory surge of luteinizing hormone (LH) in the cyclic ovulatory rat is suggested by the effect of reserpine in blocking ovulation when administered prior to, but not immediately after, the critical period of LH discharge at proestrus (4). The importance of monoaminergic pathways in the neurogenic process of LH secretion is Received January 19, 1968. 1 On leave from Department of Pharmacology, University of Uppsala, Sweden. This research was supported in part by grants from the National Institutes of Health (NB 01162 and 1 FO5-TW-1157) and the Ford Foundation. also attested by the histochemical demonstration of fine varicose catecholaminergic fibers in the median eminence in intimate relationship with the origin of the hypophysial portal vessels. The cell bodies of these nerve fibers could presumably be traced to cells of the arcuate nucleus (5, 6). Differential fluctuations in hypothalamic monoamine oxidase activity during the estrous cycle have recently been reported (7, 8). There is strong evidence that neuronal stores of monoamines (serotonin, dopamine and norepinephrine) are depleted by reserpine, primarily via inhibition of the mechanism whereby amines are stored in granules (9-12) and via subsequent deamination by the intraneuronal monoamine oxidase enzyme (13, 14). We assume as a working hypothesis that the failing discharge of ovulating hormone after reserpine treatment is related to a functional shortage of monoamines. Treatment with monoamine