Steroidogenic factor 1 gene transcription is inhibited by transforming growth factor beta.
The orphan nuclear receptor, steroidogenic factor 1 (SF-1), plays a major role in adrenal and gonadal development, as well as in sexual differentiation. It has been demonstrated that the expression of a number of genes regulated by SF-1 is inhibited by the transforming growth factor, (TGF-beta). To date, however, the influence of TGF-beta on the expression of SF-1 gene has not been reported. A Northern blot analysis with the use of a radiolabeled cDNA probe, and immunodetection with antibodies directed against SF-1, demonstrated that the Sf-1 transcript and the SF-1 protein levels were lowered by TGF-beta in Y-1 adrenocortical cells, both in untreated and adenylyl cyclase activator, forskolin-treated cells. An examination of the Sf-1 transcript stability in the presence of actinomycin D revealed no influence of TGF-beta on the rate of Sf-1 mRNA decay. Inhibition of Sf-1 expression by TGF-beta was abolished by cycloheximide, suggesting that the growth factor inhibitory effect requires ongoing protein synthesis. We conclude that in Y-1 cells TGF-beta inhibits the expression of SF-1 gene at a transcriptional level, and we postulate that the inhibitory effect of TGF-beta on steroid hormone synthesis in the adrenal cortex could be due to an attenuated transcription of Sf-1.
Lehmann
Tomasz P
TP
Department of Biochemistry and Molecular Biology, University of Medical Sciences, 6 Swiecickiego St., 60-781, Poznan, Poland.
Biernacka-Lukanty
Justyna M
JM
Trzeciak
Wieslaw H
WH
Li
Jacques Y
JY
D000302:Adrenal Cortex / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms; D000818:Animals; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D054339:Steroidogenic Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D018398:Homeodomain Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C515058:steroidogenic factor 1, mouse; D003609:Dactinomycin; D005576:Colforsin; D003513:Cycloheximide