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 preoptic area (POA). Systemic injection of naloxone (NAL) increases LH secretion 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 evaluate this hypothesis we implanted ovx rats with push pull cannula into the POA and measured GABA secretion prior to and during the preoptic application 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 (E2) to induce a negative feedback effect on LH release. Intrapreoptic application of beta-END caused a rapid decline of LH release in ovx rats which was completely reversible after termination of beta-END perfusion. Though LH levels were clearly suppressed, no change of GABA release in the POA was observed. During preoptic NAL perfusion both LH secretion and GABA release remained unaffected. Likewise, during beta-END perfusion into the POA of E2 treated rats neither LH nor GABA secretion changed. In contrast, NAL perfusion rapidly increased LH release but again this action of the opioidergic drug was not accompanied by alterations of GABA release. We conclude from these data: 1) Intrapreoptically applied beta-END inhibits LH release only in the absence of steroids. In turn, blockade of opioid receptors is effective only in the presence of steroids. Both findings indicate that in the POA opioidergic activity is low in ovx rats, but high during negative feedback of E2. 2) No changes of GABA secretion were observed during manipulations of the opioidergic tonus in the POA suggesting that both beta-END and GABA do not interact to regulate 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.
Jarry
H
H
Department of Obstetrics and Gynecology, University of Göttingen, Germany.
Leonhardt
S
S
Wuttke
W
W
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010052:Ovariectomy; D011301:Preoptic Area / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009292:Narcotic Antagonists; D009270:Naloxone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D001615:beta-Endorphin; D007986:Luteinizing Hormone