CRF Alters the Infundibular LHRH Secretory System from the Medial Preoptic Area of Female Rats: Possible Involvement of Opioid Receptors

Abstract

Corticotropin-releasing factor (CRF) is a potent factor involved in the antireproductive effects of various stressors. However, the central mechanisms by which CRF modulates the hypothalamic-pituitary-gonadal (HPG) axis are not well understood. In order to verify whether CRF is able to directly influence luteinizing hormone-releasing hormone (LHRH) secretory activity at the level of the medial preoptic area (MPOA), CRF was chronically or acutely injected bilaterally into this hypothalamic area. Ten days before the experiments, female rats were implanted with a permanent double-guide cannula which was stereotaxically positioned close to the MPOA. Chronic administration of rat CRF (rCRF) was accomplished by means of two miniosmotic pumps connected to double internal cannula. Acute bilateral infusion of rCRF into the MPOA was performed in unrestrained ovariectomized (OVX) rats and during the afternoon of proestrus. Ten minutes before rCRF treatment, antagonists of opioid receptors (mu, mu 1, or kappa) were infused bilaterally into the MPOA. Hypothalamic LHRH release as well as circulating gonadotropins were determined using a push-pull cannula implanted into the median eminence (ME), and a catheter connected to the jugular vein, respectively. Chronic rCRF treatment in the MPOA decreased (p < 0.05) plasma LH levels but did not modify follicle-stimulating hormone release in OVX rats. A significant inhibition of LH secretion was first observed 80 min after the acute rCRF infusion into the MPOA; pretreatment with nor-Binaltorphimine (antagonist of kappa-receptors) did not measurably attenuate this effect. In contrast, bilateral administration of beta-Funaltrexamine (antagonist of mu-opioid receptors) or naloxonazine (mu 1-antagonist) partially attenuated the inhibitory effect of rCRF on plasma LH levels. Similarly, injections of rCRF bilaterally into the MPOA suppressed hypothalamic LHRH release into the ME and this effect was partially reversed by a previous administration of opioid mu- or mu 1-receptor antagonists. In contrast to rCRF injection into the MPOA, administration of rCRF into the paraventricular nucleus the arcuate nucleus of the hypothalamus and directly into the ME were without significant effect on hypothalamic LHRH release in proestrus rats. In conclusion, the present data show that from among the hypothalamic sites tested, only the MPOA proved susceptible to CRF-induced alteration of LHRH neuronal activity during proestrus afternoon in rats. The release of opioids from nerve terminals located in the MPOA, which in turn binds and activates mainly type mu 1-receptors, might contribute to this inhibitory influence of CRF on LHRH release in the infundibular system.