Estrogen augments hypothalamicβ-endorphin secretion and activates an inhibitoryβ-endorphin short-loop feedback system

The role of estrogen in the regulation of hypothalamicβ-endorphin hormone secretion is studied by determiningβ-endorphin concentration in pituitary portal plasma of ovariectomized rats in the presence or absence of this steroid and/or the opioid antagonist naloxone. Twenty-six hours following s.c. injection of 10 /µg estradiol benzoate (estrogen) or oil, rats anesthetized with Saffan (alphaxolone/alphadolone) underwent pituitary stalk exposure and hypophysectomy, after which pituitary portal blood was continuously collected and stored in 15 min aliquots from 1100-1400 h. At 1100 h, animals were given an initial bolus iv injection of naloxone or saline (naloxone, 2 mg/ kg, or saline, 0.1 ml) and then infused (iv) continuously with naloxone (2 mg/kg/h) or saline (0.8 ml/h) until 1400 h. Plasma samples were extracted and assayed by radioimmunoassay forβ-endorphin. Treatment with estrogen increased the meanβ-endorphin levels twofold as compared to oil-treated controls. Naloxone potentiated estrogen action ofβ-endorphin secretion, but did not affect basalβ-endorphin secretion. These results suggest that estrogen enhancedβ-endorphin secretion from the hypothalamus. Furthermore, the hypersecretion ofβ-endorphin induced by naloxone with, but not without, estrogen supports the existence of an estrogen-activated short-loop negative feedback mechanism regulatingβ-endorphin secretion.