INFLUENCE OF CORTICOTROPIN-RELEASING FACTOR ON REPRODUCTIVE FUNCTIONS IN THE RAT

The acute administration of 0.015-1.5 nmol ovine corticotropin-releasing factor (CRF) into the lateral ventricle of gonadectomized (or gonadectomized/adrenalectomized) female rats caused a rapid and prolonged dose-related inhibition of LH [luteinizing hormone] (but not FSH) secretion. By contrast, the acute peripheral injection of up to 15 nmol CRF was without effect in the same animal preparations. In cycling intact female rats, injection of 1.5 nmol CRF into the brain or of 75 nmol CRF s.c. inhibited ovulation and blocked the proestrous LH surge in about 50% of the animals. Lower doses of peripherally administered CRF were ineffective. CRF injected daily s.c. (15 nmol/day) to female rats during the first 12 days after mating caused a 40% disruption of pregnancy. CRF will lower plasma LH levels and can exert this effect in the absence of circulating steroids of either adrenal or gonadal origin. CRF inhibition of LH secretion was unaltered by the opiate receptor antagonist naltrexone or by the ganglionic blocker chlorisondamine. Blockade of CRF-induced .beta.-endorphin or ACTH release into the general circulation by dexamethasone did not interfere with the inhibitory effect of CRF on LH secretion. CRF apparently exerts deleterious actions on reproductive functions through brain sites of action which, at least under the experimental design used, do not appear to directly involve opiate or peripheral catecholaminergic pathways.