Action of steroids on LH-RH provoked gonadotropin release.

The action of mesterolone (1 alpha-methyl-17-beta-hydroxy-5 alpha-androsten-3-one) mesterolone cipionate, testosterone, 17 alpha-methyl-testosterone, 17 beta-hydroxy-5 alpha-androstane-3-one, cyproterone actetate and D-norgestrel on basal and LH-RH stimulated, gonadotropin release was studied in vitro. Hemi-gland preparation of the anterior pituitary were incubated in the presence or absence of steroids and/or LH-RH. Steroid hormones were added at a concentration of 25, 5 and 1 mug per ml medium. Basal levels of LH and FSH discharge were not influenced by mesterolone, whereas inhibition of LH-RH stimulated gonadotropin release was noted at 25 mug mesterolone/ml medium. The addition of mesterolone cipionate to the incubation medium did not significantly change basal FSH levels, whereas an inhibition of LH-RH provoked FSH discharge was noted. Basal LH release was stimulated by the presence of 1 mug mesterolone cipionate per 1 ml medium. LH-RH stimulated LH release in the presence of 25, 5 and 1 mug mesterolone cipionate per 1 ml medium was indistinguishable from control levels. Basal levels of LH and FSH were not affected by testosterone, whereas an impaired gonadotropin response to LH-RH was observed in the presence of testosterone. At 1 mug testosterone per 1 ml medium only LH response to LH-RH was found. Basal gonadotropin levels in the presence of 17 alpha-methyl-testosterone were indistinguishable from control values. The only inhibition of LH-RH action was found for stimulation of LH release at 25 mug 17 alpha-methyl-testosterone/ml medium. On the other hand, 17 beta-hydroxy-5 alpha-androstane-3-one stimulated basal LH and FSH discharge, and LH-RH actions were not impaired. Results of our studies with cyproterone acetate indicate that this steroid stimulates basal pituitary gonadotropin discharge at high concentration, without blunting responses to LH-RH. No action of D-norgestrel on basal and LH-RH stimulated gonadotropin release was observed. These experiments add further evidence that steroids modulate LH-RH actions at the pituitary level. It is concluded that the fine control of gonadotropin release resides at the adenohypophysis whereas the coarse control of LH and FSH discharge is at the hypothalamus and/or other centers of the central nervous system.