Regulation of Genes Controlling Gonadotropin Secretion

Synthesis and secretion of gonadotropic hormones is a complex process that requires precise regulation of genes encoding for the gonadompin-releasing hormone (GnRH) receptor, the common a-subunit of glycoprotein hormones and the individual P-subunits of the gonadotropins. These genes apparently can be influenced by gonadal steroids, GnRH and other peptide hormones such as activin and inhibin. Genes for the p-subunits of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have been isolated and some information about their structures is available; however, at the time of this writing, the gene for the GnRH-receptor has not yet been isolated. Because elimination of hypothalamic input to the anterior pituitary gland is followed by a decrease.in the number of GnRH-receptors and in the quantity of messenger RNA (mRNA) for the gonadotropin subunits, it is evident that a hypothalamic substance is required for normal expression of the genes for these proteins. This hypothalamic substance is probably GnRH, because pulsatile infusion of GnRH into animals without hypothalamic input to the anterior pituitary gland restores the number of GnRH-receptors and quantities of mRNA for the subunits of gonadotropins, as well as secretion of LH. Estradiol also appears to regulate genes for the GnRH-receptor and for the subunits of LH and FSH, but in an opposing manner in that it increases the number of receptors for GnRH but decreases the concentration of mRNA for the subunits of gonadotropins. Moreover, estradiol appears to be capable of ovemding the stimulatory effect of GnRH on mRNA for the subunits of gonadotropins. In contrast to estradiol, progesterone appears to have little effect on expression of genes for the GnRH-receptor or for the gonadotropin subunits. Charcoaltreated bovine follicular fluid decreases the amount of mRNA for FSHP-subunit presumably due to the inhibin it contains) but does not influence the amount of mRNA for a-subunit or LHP-subunit. Concentrations of GnRH-receptors and mRNAs for gonadotropins subunits have been determined during the estrous cycle, gestation and postpartum anestrus. Changes in concentrations of mRNAs for gonadotropin subunits are discussed relative to the changes in concentrations of LH, FSH, estradiol and progesterone during these physiological states. Current concepts regarding our understanding of these events are depicted in Figure 1.