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 insu lin-like growth factor-I (IGF-I), follicle stimulating hormone (FSH) a nd luteinizing hormone (LH) alone and in combination on growth and pro gesterone production by human granulosa - lutein cells. Granulosa - lu tein cells were obtained from patients (n > 5) undergoing in-vitro fer tilization (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 change d every 2 days. No change in cell number (relative to each patient's o wn control) was observed after treatment with FSH or LH alone or in co mbination at any time. IGF-I alone produced a 117 +/- 8% and 176 +/- 1 5% (mean +/- SEM, n = 5) increase in cell number after 2 and 4 days re spectively. 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 tim e in culture (564, 375-1089 nmol/l, day 4). After 2 days culture proge sterone output increased by 116 +/- 5% of control in response to LH an d 153 +/- 13% (mean +/- SEM, n = 5) of control in response to IGF-I. A fter 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 an y time. FSH alone had no effect on progesterone output and did not enh ance 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 bu t that seen with IGF-I is secondary to an increase in cell number; thi rdly that FSH and LH do not synergize with IGF-I with regard to proges terone secretion, and lastly that FSH does not stimulate progesterone secretion or growth.