PHYSIOLOGICAL REGULATION OF GONADOTROPIN GENE EXPRESSION

University Of Virginia Charlottesville, Charlottesville VA

Investigators

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Abstract

DESCRIPTION (Adapted from the Investigator's Abstract): The objective of this application is to elucidate the mechanisms responsible for the differential secretion of FSH and LH. The first specific aim will test the hypothesis that the ability of specific GnRH pulse patterns to differentially stimulate FSHb and FSH secretion is mediated by changes in pituitary activin and follistatin (FS). The initial experiments will use a GnRH-deficient in vivo model to examine the effects of GnRH pulse patterns and gonadal steroids on mRNA levels of inhibin-bB, inhibin-a, and FSHb and FSH secretion. The next experiments will use in vivo and in vitro application of peptides and antisera to test the role of pituitary FS and activin in mediating the action of GnRH on FSH synthesis and secretion. The final studies in this specific aim will examine the hormonal role of inhibin by monitoring the pituitary effects of immunoneutralization of inhibin in females and test the hypothesis that testosterone blocks that action of inhibin by giving testosterone to females and anti-androgens to males. The second specific aim will make use of RT-PCR measurements of primary transcripts to assess the effect of GnRH pulse patterns and gonadal hormones on the transcription rate of the FSHb and LHb genes, using the same in vivo models as Specific Aim 1.