GnRH Pulse Frequency Modulation of Gonadotropin Subunit Gene Transcription in Normal Gonadotropes—Assessment by Primary Transcript Assay Provides Evidence for Roles of GnRH and Follistatin

Abstract

We examined the time course of action of GnRH pulse frequency on gonadotropin subunit gene transcription and assessed the roles of GnRH, follistatin (FS), and activin on differential transcription of the LHbeta and FSHbeta genes. GnRH-deficient male rats were pulsed with 25 ng GnRH either every 30 min (fast frequency) or every 240 min (slow frequency) for 1-24 h. Both GnRH frequencies increased alpha primary transcript (PT) 5-fold within 6 h, but only fast frequency GnRH increased alpha mRNA. Only fast frequency GnRH pulses affected LHbeta PT, resulting in 6- to 9-fold increases between 1-24 h. Fast frequency GnRH pulses transiently increased FSHbeta PT at 1 and 6 h (4- and 2-fold, respectively); but by 24 h FSHbeta PT had returned to control levels and was correlated to a 5- to 9-fold increase in FS mRNA. In contrast, slow GnRH pulses increased FSHbeta PT 3- and 6-fold at 8 and 24 h, respectively, which was correlated with a decline in FS mRNA. Activin mRNA did not change significantly after either GnRH frequency, but tended to fall after fast pulses. To test whether activin was required for the effects of GnRH on FSHbeta transcription, rats were treated with GnRH pulses every 240 min for 8 h +/- FS. FS treatment alone markedly decreased basal FSHbeta PT. GnRH in the presence of FS increased FSHbeta PT 8-fold but did not restore FSHbeta transcription to control or GnRH alone values. In summary, whereas alpha-subunit transcription is independent of frequency, an increase in a…