Differential Regulation of FSH(beta) Transcription by Changes in GnRH Pulse Frequency
Presenter
August 12, 2010
Abstract
The gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play an integral role in the reproductive axis, translating neural and hormonal input into precisely regulated output to achieve normal sexual development and regulation of gonadal function. In recent years, considerable progress has been made in the elucidation of the molecular mechanisms underlying tissue-specific and tonic GnRH-dependent expression of the gonadotropin (beta)-subunit genes. However, little is known about the mechanisms essential in the differential control of gonadotropin gene expression by changes in GnRH pulse frequency. The focus of this presentation is to discuss mechanisms that contribute to the GnRH pulse frequency-dependent differential control of FSH(beta) gene expression. A major GnRH-responsive site within the FSH(beta) promoter is predominantly bound by cAMP response element binding protein (CREB) to stimulate FSH(beta) transcription. In turn, the transcriptional inhibitor, inducible cAMP early repressor (ICER), is expressed to a greater extent at high GnRH pulse frequencies and antagonizes the stimulatory transcriptional effects of CREB. The experimental data supporting this dynamic model of GnRH pulse frequency-dependent regulation of FSH(beta) transcription will be presented and ongoing studies to explore mechanisms essential in integrating the effects of the bZIP transcription factors, CREB and ICER, to ultimately govern the activation of FSH(beta) gene expression will be discussed.