DIURNAL-VARIATION IN THE ACUTE EFFECTS OF ESTRADIOL AND PROGESTERONE ON BETA-ENDORPHIN AND MET-ENKEPHALIN LEVELS IN SPECIFIC BRAIN-REGIONS OF OVARIECTOMIZED RATS

The present investigation was conducted to evaluate the effects of estradiol and progesterone on beta-endorphin and Met-enkephalin levels in specific brain regions of ovariectomized rats. Female Sprague-Dawley rats (100-120g) adapted to a 12-hour light, 12-hour dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 mu g/kg in 0.2 ml olive oil) was administered subcutaneously to rats at either 8.00, 14.00 or 16.00 h, progesterone (5 mg/kg in 0.1 ml olive oil) or estradiol plus progesterone was administered subcutaneously at 16.00 h. Control rats were injected with olive oil. Animals were sacrificed 2 h later. The cerebral cortex, hypothalamus, hippocampus and midbrain were dissected, and their beta-endorphin and Met-enkephalin levels were determined by radioimmunoassay. Estradiol administration at 8.00 h resulted in a significant decline in beta-endorphin levels of the hippocampus (66% decrease) and a significant rise in Met-enkephalin levels of the hypothalamus (37.8% increase) but had no effect on other brain regions studied. When estradiol was administered at 14.00 h, it produced a significant change in beta-endorphin levels in the cerebral cortex (34.7% increase) and in the midbrain (31.3% increase), but these levels were not altered in the other brain regions. At 16.00 h estradiol and progesterone alone caused a significant increase (29 and 43%, respectively) in beta-endorphin levels of the hippocampus. Similarly, the Met-enkephalin levels in the hippocampus significantly increased following administration of estradiol (57% increase) and progesterone (54% increase) alone. However, estradiol and progesterone administered in combination produced a significant change in beta-endorphin levels in the hypothalamus (25% increase) and in the cerebral cortex (30% increase). Moreover, the Met-enkephalin levels in the cerebral cortex significantly increased with all treatments whereas these levels in the midbrain increased only when estradiol and progesterone were administered in combination. These findings indicate that estradiol and progesterone affect beta-endorphin as well as Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. In addition, the alteration in hippocampal endogenous opioid levels induced by estrogen and progesterone may in part explain their behavioral effects.