Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) gene: cell-specific expression and transcriptional regulation by androgen in transgenic mouse testis.
Gonadotropin-regulated testicular RNA helicase is a multifunctional enzyme present in both Leydig and germ cells that is essential for the progress of spermatogenesis. GRTH gene expression is transcriptionally upregulated by human chorionic gonadotropin (hCG) via second messenger (cAMP) and androgen in Leydig cells. The regulatory region(s) in the GRTH gene that is/are required for its cell-specific expression in the testis and hCG/androgen dependent expression were investigated in transgenic mice carrying sequential deletions of 5' flanking sequences of the GRTH gene. GFP-reporter gene expression directed by the GRTH 5' flanking sequences extending to -3.6 kb was specifically located in Leydig cells and the 205 bp minimal promoter domain was sufficient for this cell-specific expression. The 1 kb (5' to the ATG codon) transgene-directed expression was markedly increased by in vivo hCG treatment. Administration of the androgen receptor inhibitor Flutamide blocked the basal and hCG stimulated GFP expression in Leydig cells. We conclude that the expression of GRTH in testicular cells is differentially regulated by its 5' flanking sequence and that the 1 kb fragment of GRTH gene contains sequences for androgen regulation of its expression in Leydig cells.
Tsai-Morris
Chon-Hwa
CH
Section on Molecular Endocrinology, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA. morrisch@mail.nih.gov
Sheng
Yi
Y
Gutti
Ravi
R
Li
Jie
J
Pickel
James
J
Dufau
Maria L
ML
D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D005485:Flutamide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020365:RNA Helicases; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D059002:Androgen Receptor Antagonists; D000728:Androgens; D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005485:Flutamide; C487765:Ddx25 protein, mouse; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases