Lutropin (LH) and follitropin (FSH) are the pituitary gonadotropins which regulate sex-steroid hormone secretion and biosynthesis, and gametogenesis. In addition, LH and FSH are glycoprotein hormones that are synthesized and secreted by the gonadotrope in the anterior pituitary gland, and are essential for normal sexual development and reproduction. Each hormone is composed of two different subunits, alpha and beta, which are encoded by separate genes located on different chromosomes. The major overall objective of this work is to understand how various hormones regulate the biosynthesis of LH and FSH at the pre-translational level. The major goal of this proposal is to characterize further the hormonal regulation of expression of the LH and FSH genes in the gonadotrope.
The SPECIFIC AIMS i nclude: (1) to isolate and characterize genomic and complementary DNAs encoding the beta subunit of rat FSH; (2) to determine the regulation of the steady-state levels of alpha, LH beta, ad FSH beta subunit mRNAs under the influence of various hormones in different reproductive and endocrine physiologic states, (3) to evaluate the effect of inhibin on the synthesis of FSH at the pre-translational level in vivo and in vitro; to compare these effects with those on LH subunit mRNAs, and (4) to assess the effect of FSH-releasing peptide (FRP) on the synthesis of FSH at the pre-translational level in vitro. A minor goal will be to determine the effect of GnRH- associated peptide (GAP) on pituitary LH and FSH subunit mRNA levels in vitro. RNA levels will be determined using blot and liquid hybridization techniques, and gene activities will be determined by transcriptional rate assays. These data will be correlated with serum/medium and tissue LH and FSH levels. This knowledge will provide us with a better appreciation of the mechanisms of action of various sex-steroid hormones and regulation of gene transcriptional activity. In addition, such information will allow us to determine further the roles of these regulatory peptides and sex-steroids as they affect LH and FSH in the regulation of reproductive function with applications to fertility and contraceptive studies.
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