Pz. Tang et al., REGULATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE IN GONADOTROPIN-INDUCED STEROIDOGENIC DESENSITIZATION OF LEYDIG-CELLS, Endocrinology, 139(11), 1998, pp. 4496-4505
3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerases (SP-H
SD) are enzymes that catalyze the conversion of Delta(5) to Delta(4) s
teroids in the gonads and adrenal for the biosynthesis of sex steroid
and corticoids. In gonadotropin-desensitized Leydig cells, from rats t
reated with high doses of human CG (hCG), testosterone production is m
arkedly reduced, a finding that was attributed in part to reduction of
CYP17 expression. In this study, we present evidence for an additiona
l steroidogenic lesion induced by gonadotropin. Using differential dis
play analysis of messenger RNA (mRNA) from Leydig cells of rats treate
d with a single desensitizing dose of hCG (2.5 pg), we found that tran
scripts for type I and type II SP-HSD were substantially (5- to 8-fold
) down-regulated. This major reduction, confirmed by RNase protection
assay, was observed at the high hCG dose (2.5 mu g), whereas minor or
no change was found at lower doses (0.01 and 0.1 mu g). In contrast, 3
beta-HSD mRNA transcripts were not changed in luteinized, ovaries of
pseudopregnant rats treated with 2.5 pg hCG. The down-regulation of IP
-HSD mRNA in the Leydig cell resulted from changes at the transcriptio
nal level. Western blot analysis showed 3 beta-HSD protein was signifi
cantly reduced by hCG treatment, with changes that were coincidental w
ith the reduction of enzyme activity and temporally consistent with th
e reduction of 3 beta-HSD mRNA but independent of LH receptor down-reg
ulation. The reduction of SP-HSD mRNA resulting from transcriptional i
nhibition of gene expression, and the consequent reduction of SP-HSD a
ctivity could contribute to the inhibition of androgen production in g
onadotropin-induced steroidogenic desensitization of leydig cells. The
gender-specific regulation of 3 beta-HSD by hCG reflects differential
transcriptional regulation of the enzymes to accommodate physiologica
l hormonal requirements and reproductive function.