WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells.
Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of steroidogenic genes in response to gonadotropins is a critical mechanism that regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be essential for the differential regulation of formation of sex steroids in the ovary. Aromatase P450 (P450arom) is the rate-limiting enzyme for estrogen formation. In this study, we characterize another nuclear receptor half site in the gonadal aromatase promoter which we show to be important for aromatase regulation. We also show herein that the stimulation of P450arom promoter activity by SF-1 in ovarian granulosa, testicular Sertoli and JEG-3 choriocarcinoma cells is inhibited by two transcription factors, Wilms' tumor suppressor gene (WT1) and dosage sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Given the characterized roles of these transcription factors in gonadal development and function, modulation of SF-1 action by WT1 and DAX-1 may represent an important key mechanism in steroidogenesis.
Departments of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Illinois at Chicago, 820 S Wood Street, M/C 808, Chicago, IL 60612, USA.
Bilgin
B
Gurates
Abraham
A
Amsterdam
Mitsutoshi
M
Tamura
Sijun
S
Yang
Jianfeng
J
Zhou
Zongjuan
Z
Fang
Sanober
S
Amin
Siby
S
Sebastian
Serdar E
SE
Bulun
D020816:Amino Acid Motifs; D000818:Animals; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D016384:Consensus Sequence; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D016162:Genes, Wilms Tumor; D006066:Gonads / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D012708:Sertoli Cells / Q000378:metabolism; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D025721:WT1 Proteins / Q000502:physiology*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; C539965:NR0B1 protein, human; C515057:NR5A1 protein, human; C539966:Nr0b1 protein, mouse; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D025721:WT1 Proteins; C515058:steroidogenic factor 1, mouse; D001141:Aromatase