TRANSCRIPTION RATE OF THE FOLLICLE-STIMULATING-HORMONE (FSH) BETA SUBUNIT GENE IS REDUCED BY INHIBIN IN SHEEP BUT THIS DOES NOT FULLY EXPLAIN THE DECREASE IN MESSENGER-RNA

Studies were conducted in vitro and in vivo to determine whether or not inhibin affects the transcription rate of the gene for the beta subunit of follicle stimulating hormone (FSHbeta). Pituitary cells in primary culture were incubated with 0-3000 milli-units/ml inhibin; a dose-related decrement in mRNA was obtained but a parallel effect was not observed for the transcription rate of the FSHbeta gene in a nuclear run-on experiment. To determine effects in vivo, ovariectomized ewes were treated with saline (group 1), 75 mug inhibin 6 h before slaughter (group 2), inhibin 6 h and 12 h before slaughter (group 3) or inhibin 12 h before slaughter (group 4). In samples taken each 2 h, plasma FSH levels were seen to be maximally reduced 6 h after a single injection of inhibin; at this time mRNA levels were reduced up to 100% whereas FSHbeta gene transcription rate was reduced by 50%. A second injection at 6 h (group 3) caused a further reduction in plasma FSH levels with no additional effect on transcription rate. In those sheep killed 12 h after a single inhibin injection, transcription rate for the FSHbeta gene, cytoplasmic mRNA levels and plasma FSH concentrations had recovered. These studies show that the rapid effect of inhibin on FSHbeta mRNA levels may be due, in part, to an effect on transcription rate of the FSHbeta gene. An additional mechanism is required, however, to fully explain the inhibin effect on FSHbeta mRNA levels. These effects of inhibin have a time course which allows the maximal effect and full recovery within 12 h.