Estrogen suppresses rat gonadotropin gene transcription in vivo.

The modulation of gonadotropin gene expression in vivo by 17 beta-estradiol (E2) was investigated at the level of gonadotropin subunit gene transcription. Transcription rates were measured in isolated pituitary nuclei from untreated (control), ovariectomized (OVX), or estrogen-replaced (OVX-E2) female Sprague-Dawley rats. In control females, the average rate of alpha-subunit messenger RNA (mRNA) synthesis (161 +/- 30 ppm) was greater than the rates for either LH beta (42 +/- 17 ppm) or FSH beta (57 +/- 21 ppm). In OVX animals the synthesis rate for all three mRNAs was increased (alpha-subunit = 413 +/- 55 ppm; LH beta = 432 +/- 121 ppm; FSH beta = 204 +/- 91 ppm), but the 5- to 10-fold increases noted for LH beta were the most dramatic. Chronic E2 administration (10 micrograms/100 g BW sc daily for 7 days) suppressed these elevated transcription rates to near control values. The E2 effect occurred rapidly, with a significant suppression of all subunit transcription rates at 4 h, and a maximally suppressive effect at 24 h, at which time alpha-subunit = 30%, LH beta = 12%, and FSH beta = 26% of the mRNA synthesis rate in OVX animals. Thus, the estrogen status in vivo can affect gonadotropin subunit gene expression at the transcriptional level. Subunit gene transcription rates are regulated coordinately in a negative fashion, but LH beta mRNA synthesis is affected most dramatically.