Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig Sertoli cells

A large body of evidence suggests the existence of an intratesticular IGF s ystem complete with ligands, receptors and binding proteins (IGFBPs); the a im of the present study was to evaluate tri-iodothyronine (T-3) and retinoi c acid (RA) effects on IGFBP production by Sertoli cells. A significant dos e-dependent increase in IGFBP-4 mRNA levels was observed in Sertoli cells c ultured in the presence of physiological concentrations of T-3 or RA. This response was inhibited by cycloheximide, indicating that de novo protein sy nthesis is required, as well as by actinomycin D, suggesting that the incre ase in mRNA levels requires transcriptional activation. As shown by ligand blot assays the stimulatory effects of both agents on IGFBP-4 mRNA expressi on appears to be consistent with an enhanced synthesis and secretion of IGF BP-4, thus suggesting that the transcriptional response is transduced to th e protein level. Our data establish an important direct role for T-3 and RA in regulating IGFBP-4 expression and consequently IGF activity at the test is level.