Insulin-like growth factor (IGF) binding protein 3 in the rat testis: follicle-stimulating hormone dependence of mRNA expression and inhibition of IGF-I action on cultured Sertoli cells.
Insulin-like growth factor binding protein 3 (IGFBP-3) is the predominant IGF binding protein produced by cultured rat Sertoli cells. Previous studies have shown that FSH lowers the abundance of IGFBP-3 protein in Sertoli cell culture medium, suggesting that this binding protein has a physiological role in modulating insulin-like growth factor-I (IGF-I) activity in the testis. To characterize the physiological relevance of the FSH regulation of IGFBP-3, in this study we examined effects of FSH on IGFBP-3 mRNA expression in testes from hypophysectomized rats and in Sertoli cell culture. We then examined whether or not IGFBP-3 could alter the effects of IGF-I on cultured Sertoli cells. FSH (1-300 ng/ml) treatment of rat Sertoli cells dose-dependently decreased IGFBP-3 mRNA, with near-complete inhibition by 12 h of treatment. To evaluate this effect in the whole animal, male rats were hypophysectomized at 20 days of age and injected with FSH 10 days later. Testis IGFBP-3 mRNA increased following hypophysectomy relative to the value in sham animals, while FSH treatment decreased IGFBP-3 mRNA to sham levels within 6 h. To determine whether or not IGFBP-3 modulates IGF-I activity in the Sertoli cell, recombinant human non-glycosylated rIGFBP-3 was added to Sertoli cell cultures in the presence or absence of IGF-I. The rIGFBP-3 dose-dependently inhibited IGF-I-stimulated lactate production with a half-maximal dose of 100 ng/ml. Neither basal lactate production nor FSH-stimulated lactate was altered by addition of rIGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Rappaport
M S
MS
Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Smith
E P
EP
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006031:Glycosylation; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012708:Sertoli Cells / Q000378:metabolism*
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007773:Lactates; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone