Stimulation of Aromatase Activity by Follicle Stimulating Hormone in Rat Granulosa Cellsin Vivoandin Vitro*

Abstract
The role of FSH [follicle stimulating hormone] in the activation of aromatase enzymes in granulosa cells was studied by using immature, hypophysectomized, estrogen-primed rats as a model system. After twice daily injections of ovine FSH, aromatase activity was induced in granulosa cells after a 24 h lag period. Continued FSH treatment caused a further increase in aromatase activity. After 48 h, the enzyme activity was comparable to that found in granulosa cells of adult preovulatory follicles. The effects of enzyme substrate (androstenedione) as well as purified FSH and LH upon aromatase activity were investigated in vitro by culturing granulosa cells for 2 days in a chemically defined medium containing these hormones. In the absence of aromatase substrate, no significant stimulation of estrogen secretion was observed in control and gonadotropin-treated cultures. However, in the presence of enzyme substrate (10-7 M androstenedione), highly purified FSH (200 ng/ml), but not LH (200 ng/ml), stimulated estrogen production 8.8-and 40-fold after 1 and 2 days, respectively. The dose-response relationship between FSH and aromatase activity was studied in vitro. In the presence of androstenedione (10-7 M), increasing concentrations of FSH (0.3-100 ng/ml) resulted in a dose-related increase in estrogen production with 1 ng and 100 ng/ml FSH, causing a 6- and 80-fold increase in estrogen production, respectively. The concentration of FSH required for half-maximum estrogen production was 5 ng/ml. Without added androstenedione, no stimulation of estrogen secretion was observed during the 2-day culture period; however, when these FSH-treated cultures were washed and then reincubated for 3 h with 10-7 M androstenedione, and FSH dose-related increase in estrogen production by the granulosa cells was observed, demonstrating that FSH alone activated the aromatase enzymes. FSH stimulates aromatase enzyme activity in rat granulosa cells in vivo and in vitro, and this process is time and dose dependent.

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