Low and high concentrations of gonadotropins differentially regulate hormone production by theca interna and granulosa cells from bovine preovulatory follicles

Mammalian preovulatory follicles produce primarily estradiol and androgens before the preovulatory gonadotropin surge. In cattle, the LH/FSH surge triggers a rapid decrease in estradiol and androgen production and a dramatic increase in progesterone and oxytocin biosynthesis. It is unclear how changes in gonadotropin concentrations in vivo regulate this follicular/luteal phase shift in hormone production. To address this question, theca interna and granulosa cells were isolated from preovulatory follicles of Holstein heifers approximately 24 h before the expected time of the LH/FSH surge and cultured in defined medium containing insulin (1 microgram/ml), with varying doses of LH or FSH (0, 1, 2, 4, 8, 16, 32, 64, or 128 ng/ml). Media were collected and replaced every 24 h for 3 days, and assayed for androstenedione and progesterone in theca interna cultures, and for estradiol, progesterone and oxytocin in granulosa cell cultures. After the first day of culture (24-72 h), only very low doses of LH (2 or 4 ng/ml) enhanced (p < 0.05) androstenedione secretion by theca interna cultures above control levels, whereas progesterone secretion was increased by a wide range of LH concentrations (p < 0.05), with maximal progesterone secretion at high doses of LH. Likewise, after the first day of culture (24-72 h), estradiol secretion by granulosa cells was stimulated only by low doses of FSH and was inhibited at higher concentrations relative to control cultures (p < 0.05), whereas the production of oxytocin and progesterone was enhanced maximally by high concentrations of FSH (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)