T. Lin et al., UP-REGULATION OF HUMAN CHORIONIC GONADOTROPIN-INDUCED STEROIDOGENIC ACUTE REGULATORY PROTEIN BY INSULIN-LIKE GROWTH-FACTOR-I IN RAT LEYDIG-CELLS, ENDOCRINE, 8(1), 1998, pp. 73-78
Insulin-like growth factor-I (ICF-I) plays an essential role in reprod
uctive function. Leydig cells express specific ICF-I receptors, and IC
F-I enhances human chorionic gonadorphin (hCG)-induced testosterone fo
rmation. In the present study, we evaluate the effect of IGF-I on the
gene expression and protein levels of steroidogenic acute regulatory p
rotein (StAR), the rate-limiting step in steroidogenesis. StAR mRNA is
expressed in rat Leydig cells as two major transcripts of 3.8 and 1.7
kb. StAR mRNA levels (both 3.8 and 1.7 kb) were markedly induced abou
t 20-fold by hCG (10 ng/mL). Concomitant addition of ICF-I (50 or 100
ng/mL) and hCG (10 ng/mL) resulted in significant increases in StAR an
d cytochrome P450 side-chain cleavage (P450scc) mRNA levels, whereas l
ower doses of IGF-I (1 or 10 ng/ mt) had small effects. Synergistic ef
fects of ICF-I and hCG on StAR mRNA levels were confirmed by ribonucle
ase protection assay (RPA). ICF-I (100 ng/mL) enhanced hCG- and 20 OH-
cholesterol + hCG-induced testosterone formation, whereas the conversi
ons of pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone, and a
ndrostenedione to testosterone were not affected. This suggests that t
he major effect of IGF-I is at the steps of StAR and P450scc, whereas
other steroidogenic enzymes are not affected. To evaluate whether incr
eased StAR mRNA levels induced by ICF-I and hCG are associated with in
creased StAR protein levels, we carried out Western blot analyses. Bas
al StAR protein levels were low after 24 h in culture. hCG (10 ng/mL)
increased StAR protein by 4.5-fold. In the presence of ICF-I (100 ng/m
L), hCG-induced StAR protein levels were further increased. In conclus
ion, our present study demonstrated that ICF-I enhances Leydig cell st
eroidogenesis by upregulating hCG-induced StAR gene expression and pro
tein production.