Role of steroidogenic-factor 1 in basal and 3',5'-cyclic adenosine monophosphate-mediated regulation of cytochrome P450 side-chain cleavage enzyme in the mouse.
The orphan receptor steroidogenic factor-1 (SF-1) plays a major role in adrenal and gonadal development and sexual differentiation, and it has been shown to interact with shared promotor elements to increase the expression of cytochrome P450 side-chain cleavage (P450scc) and other steroid hydroxylases in vitro. We took a step-wise approach to define the role of SF-1 in regulation of hormone-induced steroidogenesis. In a mouse Leydig cell line (MA-10) we show that hCG and forskolin are effective inducers of progesterone production and P450scc expression. In contrast, endogenous SF-1 expression was not increased by either hCG or forskolin. Similarly, these agents did not enhance the activity of SF-1 promoter transfected into MA-10 cells. The transcriptional activity of SF-1, measured by induction of an SF-1 synthetic reporter, was only minimally increased by forskolin. Within the context of the rat P450SCC promoter, mutation of the two SF-1-binding sites caused a dramatic decrease in constitutive activity of this promoter, but the degree of induction by 8-bromo-cAMP was only reduced from 7.9-fold to 5.9-fold. We conclude that SF-1 is required for the constitutive activity of P450scc, but that it does not play a direct role in the early induction of steroidogenesis by hCG or forskolin in MA-10 cells.
Chau
Y M
YM
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Crawford
P A
PA
Woodson
K G
KG
Polish
J A
JA
Olson
L M
LM
Sadovsky
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis* / Q000235:genetics; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins; D051379:Mice; D009154:Mutation / Q000502:physiology; D011374:Progesterone / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000502:physiology*
D006063:Chorionic Gonadotropin; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme