Insulin-like growth factor-II mediates the steroidogenic and growth promoting actions of follicle stimulating hormone on human ovarian pre-antral follicles cultured in vitro.
FSH is important for ovarian antral follicle growth and steroidogenesis, processes in the human that are believed to be mediated by IGF-II. The objective of this study was to determine if human ovarian pre-antral follicles are also FSH- and IGF-II-responsive, since the clinical questions and mechanisms underlying the effects on the pre-antral follicle pool of exogenously administered gonadotropins for fertility therapy and elevated endogenous gonadotropins in the perimenopause remain unanswered. Class 2 preantral follicles were isolated from human premenopausal ovaries (n=6) and cultured in vitro with androstenedione and either no additives or with FSH or IGF-II. FSH (100 ng/mL) stimulated estradiol (E2) production by 3.58 +/- 0.4 fold over 48 hr, compared to controls without FSH. This effect was completely inhibited in the presence of the IGF-II antagonist, IGF binding protein-4 (IGFBP-4). IGF-II also stimulated E2 production by preantral follicles with doses as low as 1 ng/mL and within 24 hr of treatment. Maximal response of 3- to 9-fold above control was achieved with 100 ng/mL of IGF-II between 96-120 hr of culture. IGFBP-4 completely inhibited E2 production to basal levels. FSH stimulated IGF-II mRNA in pre-antral follicles about 4-fold, determined by RT-PCR. FSH also stimulated follicle growth, determined by light microscopy, 50-68% over 48 hr, compared to controls (P<0.001), a process that was inhibited in the presence of IGFBP-4. Cumulatively, these data support IGF-II as a mediator of FSH action on human preantral follicles.
Yuan
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Department of Gynecology and Obstetrics, Stanford University School of Medicine, CA 94305-5317, USA.
Giudice
L C
LC
D000328:Adult; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000502:physiology*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D004958:Estradiol; D007335:Insulin-Like Growth Factor II; D005640:Follicle Stimulating Hormone