Administration of gonadal steroids to the castrated male rat prevents a decrease in the release of gonadotropin-releasing hormone from the incubated hypothalamus.

The influence of testosterone on gonadotropin-releasing hormone (GnRH) secretion was assessed indirectly by altering the serum testosterone concentration of male rats and measuring GnRH release from their incubated hypothalami 1 wk later.GnRH release from hypothalami of castrated rats was 13.4+/-1.2 (SE) pg/h, compared to 35.3+/-3.8 pg/h from hypothalami of intact rats (P < 0.001). GnRH release from the hypothalami of castrated rats treated with testosterone propionate, 100 or 500 mug daily, was 25.0+/-3.4 pg/h and 27.9+/-3.6 pg/h, which is significantly greater (P < 0.05 and P < 0.01, respectively) than that from hypothalami of castrated rats treated only with sesame oil.A similar decrease in GnRH release from hypothalami of hypophysectomized rats and prevention of this decrease by treating the hypophysectomized rats with testosterone propionate is evidence that the observed effects of testosterone are not mediated via luteinizing hormone and(or) follicle-stimulating hormone secretion. Treatment of castrated rats with either dihydrotestosterone propionate or estradiol benzoate also prevented the decrease in GnRH release from the hypothalami of castrated rats. We conclude that testosterone, dihydrotestosterone, and estradiol all prevent the decrease in GnRH release from hypothalami of castrated rats treated with these steroids. The possibility exists that these steroids may also maintain GnRH secretion in vivo.

Gonadotropin releasing hormone release from the rat hypothalamus: dependence on membrane depolarization and calcium influx.

Release of gonadotropin-releasing hormone (GnRH) was studied by incubating individual rat hypothalami for 60 min, after a 30-min preincubation period, and measuring GnRH in the medium by immunoassay. During the 1 h of incubation, endogenous GnRH release was linear and exogenous GnRH was not destroyed. Membrane depolarization produced by increasing the medium potassium concentration to 60 mM increased GnRH release to 200-500% of control. Membrane depolarization produced by adding 10(-5) or 10(-4) M ouabain increased GnRH release to 200% of control. Melatonin (10(-7) M) and prostaglandin E2 (4 X 10(-4) M) Aslo stimulated GnRH release to 200% and 170% of control, respectively. Inhibition of calcium influx by omission of medium calcium and addition of 0.05 M EDTA reduced GnRH release to 50% of control. Both no calcium-EDTA medium and verapamil (10(-5) M) prevented the stimulation of GnRH release by 60 mM potassium, 10(-3) M melatonin, and 4 X 10(-4) M prostaglandin E2. We conclude that hypothalamic GnRH release depends on membrane depolarization and calcium influx, as does the secretion of hormones from other endocrine tissues.