title: Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis.
abstract: Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the theca layer. Theca cells provide the androgen substrate for aromatization and estrogen production by granulosa cells. Using biologically active recombinant GDF-9 (rGDF-9) and an androgen-producing immortalized theca-interstitial cell (TIC) line or primary TIC, we have examined the action of this paracrine hormone on theca cell steroidogenesis. The effect of GDF-9 on TIC progesterone synthesis was marginal and inconsistent in the primary cultures. In immortalized theca cells, GDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanced both basal and stimulated androstenedione accumulation in the primary and transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preovulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte product, on TIC androgen production suggests a regulatory role of the oocyte on theca cell function and hence on follicle development and differentiation. This direct effect of GDF-9 on thecal steroidogenesis is consistent with its recently demonstrated actions on thecal cell recruitment and differentiation.
authors.affiliation: Bernhard Zondek Hormone Research Laboratory, Department of Biological Regulation and Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: E V
authors.initials: EV
authors.lastname: Solovyeva
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Margi
authors.forename: C
authors.initials: C
authors.lastname: Barkats
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Amsterdam
authors.forename: A J
authors.initials: AJ
authors.lastname: Hsueh
authors.forename: A
authors.initials: A
authors.lastname: Tsafriri
mesh_terms: D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002460:Cell Line; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000728:Androgens; C525904:Bmp15 protein, rat; D055430:Bone Morphogenetic Protein 15; C525899:Gdf9 protein, rat; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D005576:Colforsin; D011374:Progesterone; D013254:Steroid 17-alpha-Hydroxylase