Role of nuclear receptors in INSL3 gene transcription in Leydig cells.
Insulin-like 3 (INSL3) is a hormone produced by testicular Leydig cells throughout life. During embryonic life it regulates an essential step of testicular descent, whereas in adults it acts as a male germ cell survival factor. Despite the importance of INSL3 for male sex differentiation and function, very little is known regarding the molecular mechanisms that regulate its expression. So far, the nuclear receptor SF-1 is the only transcription factor known to regulate the mouse Insl3 promoter in Leydig cells. In order to further our understanding of the transcriptional regulation of INSL3 expression, we have isolated the human INSL3 promoter and tested the effects of the nuclear receptors SF-1, LRH-1, and Nur77 on its activity in Leydig cells. In transfections assays, all three nuclear receptors activated the human INSL3 promoter but especially Nur77, which acted through a novel regulatory element. Thus, the human INSL3 promoter constitutes a novel target for the orphan nuclear receptor Nur77.
Ontogeny-Reproduction Research Unit, CHUL Research Centre, 2705 Laurier Blvd., Ste-Foy, Québec, Canada G1V 4G2. Jacques-J.Tremblay@crchul.ulaval.ca
Jacques J
JJ
Tremblay
Nicholas M
NM
Robert
D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007328:Insulin; C084797:Leydig insulin-like protein; C539821:NR4A1 protein, human; C082631:NR5A2 protein, human; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors