title: Insulin-like growth factor I inhibits aromatization induced by follice-stimulating hormone in rat sertoli cell culture.
abstract: Sertoli cells in the testis and granulosa cells in the ovary convert androgen to estrogen under the primary control of FSH. Insulin-like growth factor I (IGF-I) markedly augments FSH-stimulated estrogen production in the rat granulosa cell. In this study we examined the regulation of aromatase by FSH and characterized the effects of IGF-I on FSH-induced estrogen production by Sertoli cells cultured from the testes of 16-day-old rats. FSH stimulated aromatization of androstenedione in Sertoli cell culture and achieved maximal effectiveness by 12 h of treatment. Analysis of aromatase mRNA by reverse transcription-polymerase chain reaction indicated a marked induction by FSH within 3 h of treatment that was dependent on FSH concentration. IGF-I inhibited FSH-stimulated aromatization dose-dependently; inhibition was approximately 50% by 6 h of cotreatment (p < 0.01). IGF-I was ineffective if added more than 3 h after addition of FSH. Aromatase mRNA was reduced by IGF-I (37 +/- 12%, p < 0.01), coincident with the decrease in estrogen production. To further address the mechanism of IGF-I inhibition, potential interactions with the cAMP and protein kinase C (PKC) signaling pathways were examined. IGF-I inhibited aromatase activity induced by dibutyryl cAMP and inhibited FSH-stimulated estrogen production in the presence of 3-isobutyl-1-methylxanthine, suggesting that IGF-I action was independent of cAMP production. Phorbol-12-myristate-13-acetate (PMA) and IGF-I were additive in their inhibition of FSH. However, down-regulation of PKC prevented PMA inhibition of FSH but not inhibition by IGF-I. We conclude that IGF-I specifically inhibits FSH-induced aromatization in the Sertoli cell in marked contrast to the effects of IGF-I on rat granulosa cells. Although IGF-I and PMA both inhibit aromatase induction, the independence of the IGF-I effect from PKC down-regulation suggests that the initial action of IGF-I is independent of PKC. As IGF-I treatment similarly alters FSH stimulation of both estrogen production and aromatase mRNA, it is likely that the effect of IGF-I on estrogen production in the Sertoli cell is a result, at least in part, of a decrease in aromatase mRNA.
authors.affiliation: Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Rappaport
authors.forename: E P
authors.initials: EP
authors.lastname: Smith
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors; D001483:Base Sequence; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000201:enzymology*
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D001141:Aromatase; D011493:Protein Kinase C