Potent inhibition of human ovarian steroidogenesis by insulin-like growth factor binding protein-4 (IGFBP-4).
Several studies have now documented the existence of IGFBPs in follicular fluid and their correlation with the health of the follicle. In particular, increased levels of IGFBP-4 have been reported in androgen-dominant atretic follicles and those from polycystic ovaries. The aim of this study was to elucidate the role of IGFBP-4 in ovarian steroidogenesis. Granulosa cells and theca tissue were incubated with or without LH or FSH in the presence or absence of IGFBP-4 (0.5-50 ng/ml). Inhibition by IGFBP-4 of estradiol production in the presence of testosterone alone was seen in three of four experiments. IGFBP-4 completely inhibited FSH-stimulated estradiol production in three experiments and caused 67% inhibition in a fourth. Similar results were obtained for theca, in which concurrent incubation with IGFBP-4 completely negated the stimulatory effects of LH on androstenedione production. The mechanism by which IGFBP-4 exerts these potent effects and the possibility that this may by IGF-independent are currently being investigated.
Mason
H D
HD
Department of Obstetrics and Gynaecology, Imperial College School of Medicine at St. Mary's, Paddington, London, UK.
Cwyfan-Hughes
S
S
Holly
J M
JM
Franks
S
S
D000735:Androstenedione / Q000096:biosynthesis*; D002478:Cells, Cultured; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism*
D018974:Insulin-Like Growth Factor Binding Protein 4; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone