Regulation of luteinizing hormone-beta and follicle-stimulating hormone (FSH)-beta gene transcription by androgens: testosterone directly stimulates FSH-beta transcription independent from its role on follistatin gene expression.
The gonadotropin beta-subunit mRNAs are differentially regulated by androgens. Testosterone (T) suppresses LH-beta and increases FSH-beta. We aimed to determine whether androgens regulate LH-beta and FSH-beta transcription [as measured by changes in primary transcript (PT)] and to determine whether androgens act directly on FSH-beta or via the intrapituitary activin/follistatin (FS) system. In castrate + GnRH antagonist-treated rats, T increased FSH-beta PT between 3 and 48 h. In contrast, T suppressed LH-beta PT. The increases in FSH-beta mRNA and PT were associated with reduced FS mRNA. Activin betaB mRNA was modestly suppressed. The increase in FSH-beta PT after T was androgen specific. Both T and dihydrotestosterone (DHT) increased FSH-beta PT 2-fold and decreased both FS and betaB mRNA. Estradiol suppressed FSH-beta PT 3-fold and had no effect on FS or betaB mRNAs. LH-beta PT was suppressed by DHT. To determine whether T stimulation of FSH-beta PT reflected a decrease in pituitary FS, we gave androgen in the presence of exogenous FS in vitro. T and DHT increased FSH-beta PT 2- to 3-fold. FS alone decreased FSH-beta PT 40% but did not diminish the increase FSH-beta PT in response to T. T, DHT, and FS did not affect FS mRNA, betaB mRNA, or LH-beta PT. In conclusion, androgens acting directly on the pituitary increase FSH-beta and decrease LH-beta transcription. The increase in FSH-beta PT in response to T was androgen specific and occurs in the presence of excess FS, suggesting that T stimulates FSH-beta transcription independently of modulation of FS.
D000818:Animals; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics*; D038681:Follistatin / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000172:deficiency / Q000494:pharmacology; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D008297:Male; D009919:Orchiectomy; D010902:Pituitary Gland / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D037201:Follicle Stimulating Hormone, beta Subunit; D038681:Follistatin; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone