COMPARATIVE EFFECTS OF SHORT-TERM TREATMENT WITH NORETHISTERONE AND SEX STEROIDS ON GONADOTROPIN-SECRETION IN RAT PITUITARY CELL-CULTURES

The short term effects of norethisterone (NET), progesterone (P), estr adiol (E2) and dihydrotestosterone (DHT) on the gonadotropin secretion of pituitary cells, from both male and female rats, in primary cultur e primed with E2 were studied. In female cells, NET only increased the GnRH-induced secretion of LH, while P increased both LH and FSH. Male pituitary cells showed an increased response to GnRH after P pretreat ment only if the E2 concentration was augmented. However with the same E2 conditions pretreatment with NET decreased the stimulated LH, but not FSH secretion. Pretreatment with E2 inhibited LH stimulated secret ion from pituitary cells of male but not female rats. Furthermore DHT treatment diminished the GnRH response for both LH and FSH in pituitar y cells from both sexes. Androgen pretreatment increased basal gonadot ropin secretion in male but not in female cells. Basal FSH secretion w as increased by NET pretreatment in male cells. This suggests that NET is metabolized by cultured pituitary cells to A-ring reduced compound s during the 4 h incubation period. The formation of NET metabolites, particulary the 3beta, 5alpha and 5alpha-NET might be responsible for the estrogenic and androgenic effects observed when NET was administer ed to the cultured pituitary cells.