INSULIN-LIKE GROWTH FACTOR-I STIMULATED GROWTH AND PROGESTERONE PRODUCTION BY GRANULOSA LUTEIN CELLS - LACK OF INTERACTION WITH PHYSIOLOGICAL CONCENTRATIONS OF LUTEINIZING-HORMONE AND FOLLICLE-STIMULATING-HORMONE

This study examined the effect of physiological concentrations of insulin-like growth factor-I (IGF-I), follicle stimulating hormone (FSH) and luteinizing hormone (LH) alone and in combination on growth and progesterone production by human granulosa - lutein cells. Granulosa - lutein cells were obtained from patients (n > 5) undergoing in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) treatment. Cells were cultured for 2 and 4 days in the presence of physiological concentrations of human LH (code 68/40, 5 IU/1), FSH (code 83/575, 20 IU/1), or IGF-I (30 ng/ml) alone and in combination. Medium was changed every 2 days. No change in cell number (relative to each patient's own control) was observed after treatment with FSH or LH alone or in combination at any time. IGF-I alone produced a 117 +/- 8% and 176 +/- 15% (mean +/- SEM, n = 5) increase in cell number after 2 and 4 days respectively. This increase was unaffected by the addition of LH or FSH at any time. Basal progesterone secretion was variable (1633, 975-2409 nmol/l, median and interquartile range, day 2) and decreased with time in culture (564, 375-1089 nmol/l, day 4). After 2 days culture progesterone output increased by 116 +/- 5% of control in response to LH and 153 +/- 13% (mean +/- SEM, n = 5) of control in response to IGF-I. After 4 days, LH and IGF-I stimulated progesterone levels by 279 +/- 52% and 264 +/- 37% (mean +/- SEM, n = 5) respectively. IGF-I stimulated progesterone output was unaffected by the addition of LH or FSH at any time. FSH alone had no effect on progesterone output and did not enhance the stimulation by LH. We conclude firstly that IGF-I stimulates the growth of granulosa-lutein cells but this growth is unaffected by LH or FSH; secondly that progesterone secretion is stimulated by LH but that seen with IGF-I is secondary to an increase in cell number; thirdly that FSH and LH do not synergize with IGF-I with regard to progesterone secretion, and lastly that FSH does not stimulate progesterone secretion or growth.