The inhibitory effect of β-endorphin on LH release in ovariectomized rats does not involve the preoptic GABAergic system

Summary

In rats, ß-endorphin (ß-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 ß-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 ß-END caused a rapid decline of LH release in ovx rats which was completely reversible after termination of ß-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 ß-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 ß-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 ß-END and GABA do not interact to regulate LH release. Thus, ß-END may directly inhibit the activity of GnRH neurons located in the POA or acts via a neurotransmitter other than GABA.

Key words

GnRH - preoptic/anterior hypothalamic area - endogenous opioids - GABA - interaction