Molecular Mechanisms of the Regulation of Gonadotropin Gene Expression by Gonadotropin-releasing Hormone

Luteinizing (LH) and follicle-stimulating (FSH) hormones regulate gonadal function and gametogenesis, and are critical for normal sexual maturation and reproductive function. LH and FSH are synthesized and secreted from pituitary gonadotropes under the regulation of the hypothalamic peptide, gonadotropin-releasing hormone (GnRH). GnRH is released from the hypothalamus in a pulsatile fashion, with the frequency of release varying with the stage of development and throughout the menstrual or estrous cycle. Different pulse frequencies regulate differentially LH and FSH biosynthesis and secretion. Varying cell surface densities of GnRHR result in the differential regulation of LH and FSH subunit gene expression by GnRH. This suggests that the in vivo effects of different GnRH pulse frequencies may, in turn, be mediated by varying cell surface GnRHR concentrations. Several DNA elements and transcription factors have been identified that appear to be involved in mediating the effects of GnRH on gonadotropin subunit gene transcription.