Characterization and regulation of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) receptors on cultured pig Leydig cells. Effects of Sm-C/IGF-I on luteotropin receptors and steroidogenesis.
We have characterized somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) receptors in cultured pig Leydig cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell were 1.8 +/- 0.2 X 10(-9) M and 12,200 +/- 3200 respectively. Under reducing conditions, disuccinimidyl suberate cross-linked 125I-Sm-C to one receptor complex with apparent Mr = 120,000. Continuous treatment of Leydig cells with increasing concentrations of human chorionic gonadotropin (hCG) for 48 h resulted in a dose-dependent (ED50 0.05 nM) increment in IGF type I receptors (2.5-3-fold increase). Conversely, treatment of Leydig cells for 48 h with increasing concentrations of Sm-C/IGF-I produced a 3-4-fold increase in hCG receptors. This effect was dose-dependent (ED50 = 7 ng/ml). Sm-C/IGF-I treatment also enhanced Leydig cell responsiveness to hCG for both cAMP (6-fold) and testosterone (8-fold). Moreover the stimulatory effects of Sm-C/IGF-I on cells cultured either in the absence or presence of 5% human serum from an hypopituitary patient were inhibited by anti-(Sm-C/IGF-I) antibodies. Taken together these results not only show that Leydig cells must be considered as targets for Sm-C/IGF-I, but also lend support to the possibility that Sm-C/IGF-I plays a role in the regulation of Leydig cell function. Moreover, they suggest that Sm-C/IGF-I might be responsible for the delayed puberty observed in some patients with isolated growth hormone deficiency.
D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011284:Pregnenolone / Q000096:biosynthesis*; D011972:Receptor, Insulin / Q000378:metabolism*; D011974:Receptors, LH / Q000187:drug effects / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D013552:Swine; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D017451:Receptors, Somatomedin; D013002:Somatomedins; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D011284:Pregnenolone; D000242:Cyclic AMP; D011972:Receptor, Insulin