The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway.

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Burger LL, Haisenleder DJ, Wotton GM, Aylor KW, Dalkin AC, Marshall JC

The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway.

Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E277-85. Epub 2007 Apr 3.

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17405825 [ View in PubMed

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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.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nandrolone phenpropionate	Androgen receptor	Protein	Humans	Yes	Agonist	Details