Gonadotrophic control of steroidogenesis in human granulosa-lutein cells
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Summary. Granulosa-lutein cells were harvested from periovulatory follicles in human ovaries and cultured for up to 6 days, equivalent to almost half of a normal luteal phase. The average rate of basal progesterone accumulation in the culture medium was constant at ∼ 36 nmol progesterone/106 cells/day. Oestradiol accumulation was too low to measure in the absence of precursor androgen. Basal aromatase activity (measured as oestradiol formed in 3 h from 10−6m exogenous testosterone) was high (average 1·15 nmol oestradiol/106 cells/3 h) at the time of cell isolation (Day 0) but fell by >90% on Day 1. By Day 2 the activity had partly recovered and averaged 62% of the Day 0 value, rising to 70% on Day 6. This loss and recovery of aromatase activity was independent of the addition of gonadotrophic hormones to the culture medium. However, dose-related increases in aromatase activity occurred in the presence of highly pure human pituitary LH (0·1–30 ng/ml). The increase was observed on Day 4 and was maximal on Day 6 (average 3-fold increase over control) in the presence of LH concentrations ≥ 1·0 ng/ml. LH also caused dose-related increases in progesterone accumulation by Day 4 with maximal stimulation on Day 6 (average 3-fold increase over control) at ≥ 10·0ng/ml. Dose-related stimulation of aromatase activity by human pituitary FSH also occurred but maximal stimulation required the presence of 300 ng FSH/ml and progesterone accumulation was hardly affected at this dose. Small contaminating amounts of LH in the FSH preparation ( ∼ 0·5% on a mass basis) may have caused this stimulation but a specific FSH action was not ruled out. These results demonstrate time-related changes in steroidogenic potential with enhanced sensitivity to LH as human granulosa-lutein cells age in culture. Since fully luteinized granulosa cells retain an LH-responsive aromatase system, they may play a central role in LH-controlled oestrogen biosynthesis in the corpus luteum.
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