Hormonal Regulation of Progesterone Secretion by Cultured Mouse Granulosa Cells 1

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Abstract
Secretion of progesterone by granulosa cells from preovulatory follicles of muce was determined during 2 wk of cell culture in the presence of androgens, estrogen and pituitary gonadotropins. Androstenedione (10-7 M) and dihydrotestosterone (10-7 M) stimulated (P < 0.05) progesterone secretion during the first 11 days of culture. In contrast, 17.beta.-estradiol (10-11 to 10-7 M) did not alter (P > 0.10) progesterone secretion throughout the culture period. Luteinizing hormone (LH) and FSH stimulated (P < 0.01) the granulosa cells in a dose-dependent manner during the 1st few days of culture. This luteotropic effect was rapidly lost and at later times when FSH was not effective, LH suppressed (P < 0.05) progesterone secretion. In the presence of prolactin (Prl) (1 .mu.g/ml), granulosa cells progressively secreted more progesterone during the 1st week of culture. After maximal stimulation on Days 7-9, progesterone secretion by Prl-treated cells began to decline, but the amount of steroid produced on Day 13 was still higher (P < 0.05) than in control cultures. Androstenedione and Prl gave an additive effect on progesterone secretion during Days 3-5 of culture. Thereafter, the androgen, although stimulatory by itself, did not influence the luteotropic action of Prl. Unlike the early effect of androgens, 17.beta.-estradiol acted synergistically with Prl to maintain maximal secretion of progesterone during the last 4 days of culture. Prl apparently is the primary luteotropic hormone for mouse granulosa-lutein cells during the 1st week of their functional life span, LH may be luteolytic for mouse granulosa cells. Androgens can directly stimulate progesterone secretion by mouse granulosa cells. At a time when the cells are becoming less responsive to Prl they become dependent on estrogen for a prolonged maintenance of progesterone secretion. The requirement for estrogen at this time apparently cannot be satisfied by aromatization of androgens within the luteinized granulosa cells.