Inhibition of Luteinizing Hormone Secretion in the Ewe by Progesterone: Associated Changes in the Release of Gamma‐Aminobutyric Acid and Noradrenaline in the Preoptic Area as Measured by Intracranial Microdialysis

Abstract

Progesterone inhibits the pulsatile release of luteinizing hormone (LH) in sheep by an action in the brain to suppress the release of LH-releasing hormone (LHRH). In addition, progesterone blocks the preovulatory surge of LH in this species. The neural basis of this inhibitory action is unknown, but as LHRH cells do not appear to contain progestin receptors other neural systems must mediate the action of this ovarian steroid on LH release. This study focuses on a possible role for the inhibitory amino-acid GABA and the monoamines (noradrenaline, adrenaline, dopamine and serotonin). The technique of microdialysis was used to monitor changes in these substances in the vicinity of the LHRH cell bodies (in the preoptic area) both before and following the administration of progesterone. Levels of this steroid, similar to those measured during the mid-luteal phase of the oestrous cycle, inhibited LH release and this was associated with significant alterations in the release of GABA and noradrenaline (but not adrenaline, dopamine or serotonin). Specifically, progesterone augmented GABA while noradrenaline release was depressed. Whether steroid actions on these neurotransmitters were mediated by opioids was also investigated. This possibility arises because of the reported involvement of opioids in progesterone negative feedback in the ewe. The long-acting opioid antagonist, naltrexone, was administered and GABA and noradrenaline release monitored for a further period both in the presence and absence of progesterone. Naltrexone significantly depressed GABA release in steroid-treated (but not untreated) ewes suggesting that the actions of progesterone on GABA are mediated by the endogenous opioid peptides. However, noradrenaline release was unaltered. In an earlier study we demonstrated that GABA release fell prior to the LH surge while noradrenaline release increased. These data, in conjunction with those from the present study, suggest that the mechanism by which progesterone is able to inhibit the preovulatory surge of LH in the ewe is by enhancing GABA and depressing noradrenaline release in the vicinity of the LHRH cell bodies. As opioid tone is also reported to fall prior to the surge, the interaction between opiate and GABAergic systems in the regulation of gonadotrophin secretion warrants further investigation.