THE INHIBITORY EFFECT OF BETA-ENDORPHIN ON LH-RELEASE IN OVARIECTOMIZED RATS DOES NOT INVOLVE THE PREOPTIC GABAERGIC SYSTEM

In rats, beta-endorphin (beta-END) and gamma-aminobutyric acid (GABA) suppress LH secretion by hypothalamic mechanisms involving the preopti c area (POA). Systemic injection of naloxone (NAL) increases LH secret ion in male rats, an effect which can be prevented by coadministration of GABA agonists. Application of NAL into the POA of ovariectomized ( ovx), progesterone substituted sheep modulates preoptic GABA release. These findings have been interpreted such that the endogenous opioids act via the preoptic GABAergic system to regulate LH release. To evalu ate this hypothesis we implanted ovx rats with push pull cannula into the POA and measured GABA secretion prior to and during the preoptic a pplication of either NAL or beta-END. Blood samples were collected to assess the effects of the drugs on LH secretion. In addition, ovx rats were substituted with estradiol (E(2)) to induce a negative feedback effect on LH release. Intrapreoptic application of beta-END caused a r apid decline of LH release in ovx rats which was completely reversible after termination of beta-END perfusion. Though LH levels were clearl y suppressed, no change of GABA release in the POA was observed. Durin g preoptic NAL perfusion both LH secretion and GABA release remained u naffected. Likewise, during beta-END perfusion into the POA of E(2) tr eated rats neither LH nor GABA secretion changed. In contrast, NAL per fusion rapidly increased LK release but again this action of the opioi dergic drug was not accompanied by alterations of GABA release. We con clude from these data: 1) Intrapreoptically applied beta-END inhibits LH release only in the absence of steroids. In turn, blockade of opioi d receptors is effective only in the presence of steroids. Both findin gs indicate that in the POA opioidergic activity is low in ovx rats, b ut high during negative feedback of E(2). 2) No changes of GABA secret ion were observed during manipulations of the opioidergic tonus in the POA suggesting that both beta-END and GABA do not interact to regulat e LH release. Thus, beta-END may directly inhibit the activity of GnRH neurons located in the POA or acts via a neurotransmitter other than GABA.