Effects of insulin-like growth factor-II on proliferation and differentiation of ovarian granulosa cells.
The effects of insulin-like growth factor-II (IGF-II) on the proliferation and differentiation of ovarian granulosa cells were studied in cultured human and porcine granulosa cells. IGF-II significantly increased basal progesterone secretion in granulosa cells at concentrations of 1-100 ng/ml. A stimulatory effect was also observed in gonadotropin-stimulated porcine granulosa cells treated with IGF-II. The secretion of estradiol by basal and gonadotropin-stimulated porcine granulosa cells was also significantly increased by adding IGF-II. IGF-II led to dose-dependent increases in [3H]thymidine incorporation into DNA and in the number of granulosa cells. To further characterize the cellular mechanisms underlying the stimulatory effects of IGF-II on the proliferation and differentiation of granulosa cells, we investigated the intermediary roles of cyclic AMP and intracellular Ca2+ concentration ([Ca2+]i). Treatment with 100 ng/ml IGF-II produced a significant increase in the basal accumulation of cyclic AMP in porcine granulosa cells. However, no change of [Ca2+]i by IGF-II was noted. IGF-II produced effects in accumulation that were similar to those of IGF-I. Our findings suggest that IGF-II may be a general stimulator in the proliferation and differentiation of granulosa cells, and that cyclic AMP may be a second messenger for the effects of IGF-II in ovarian granulosa cells.
Kamada
S
S
Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Japan.
Kubota
T
T
Taguchi
M
M
Ho
W R
WR
Sakamoto
S
S
Aso
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis; D015398:Signal Transduction; D013552:Swine
D006063:Chorionic Gonadotropin; D011374:Progesterone; D004958:Estradiol; D007335:Insulin-Like Growth Factor II; D005640:Follicle Stimulating Hormone; D004247:DNA; D000242:Cyclic AMP; D002118:Calcium