title: The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway.
abstract: Recent reports suggest that androgens increase FSHbeta transcription directly via the androgen receptor and by modulating activin signaling. Estrogens may also regulate FSHbeta transcription in part through the activin system. Activin signaling can be regulated extracellularly via activin, inhibin, or follistatin (FS) or intracellularly via the Smad proteins. We determined the effects of androgen and estrogen on FSHbeta primary transcript (PT) concentrations in male and female rats, and we correlated those changes with pituitary: activin betaB mRNA, FS mRNA, the mRNAs for Smads2, -3, -4, and -7, and the phosphorylation (p) status of Smad2 and -3 proteins. In males, testosterone (T) increased FSHbeta PT two- to threefold between 3 and 24 h and was correlated with reduced FS mRNA, transient increases in Smad2, -4, and -7 mRNAs, and a six- to 10-fold increase in pSmad2, and activin betaB mRNA was unchanged. In females, T also increased FSHbeta PT twofold and pSmad2 threefold but had no effect on activin betaB, FS, or the Smad mRNAs. Androgen also increased Smad2 phosphorylation in gonadotrope-derived alphaT3 cells. In contrast, estradiol had no effect on FSHbeta PT but transiently increased activin betaB mRNA and suppressed FS mRNA before increasing FS mRNA at 24 h and increased Smads2, -3, and -7 mRNAs and pSmad2 threefold. In conclusion, T acts on the pituitary to increase FSHbeta PT in both sexes and modulates FS mRNA, Smad mRNAs, and/or Smad2 phosphorylation. These findings suggest that T regulates FSHbeta transcription, in part, through modulation of various components of the activin-signaling system.
authors.affiliation: University of Virginia, Department of Internal Medicine, P. O. Box 801412, Charlottesville, VA 22908, USA. lburger@virginia.edu
authors.forename: Laura L
authors.initials: LL
authors.lastname: Burger
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haisenleder
authors.forename: Gordon M
authors.initials: GM
authors.lastname: Wotton
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Aylor
authors.forename: Alan C
authors.initials: AC
authors.lastname: Dalkin
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D012739:Gonadal Steroid Hormones; D028341:Activins; D013739:Testosterone; D004958:Estradiol