Gonadotropin-releasing hormone (GnRH) is released from the hypothalamus and has its primary effects at the level of the anterior pituitary gland to release the gonadotropins, luteinizing hormone and follicle-stimulating hormone. Analogs of GnRH are used clinically for assisted fertility and to treat a number of diseases including precocious puberty and prostate cancer. Successful treatment with analogs of GnRH depends upon desensitization of the pituitary gland to GnRH. This effect is mediated, in part, by a decrease in the number of receptors for GnRH. Several studies have characterized changes in steady-state levels of GnRH-receptors, however, have not identified the specific mechanism(s) by which modulators of GnRH-receptor number have their effects (i.e., changes in synthesis and degradation of GnRH-receptors). Therefore, it is the overall objective of this proposal to characterize the regulation of steady state levels of receptors for GnRH in the pituitary gonadotrope. Specific objectives include 1) determination of the basal rates of synthesis and degradation of GnRH-receptors, 2) identification of the effects of gonadal influence on these rates, 3) characterization of developmental changes in synthesis and degradation of GnRH receptors, and 4) determination of influence of stage of the reproductive cycle on the rates. As no specific probes are available to identify solubilized GnRH-receptors for usual methods of measuring synthesis and degradation of proteins, we will adapt the density shift technique combined with photoaffinity labeling to determine these rates. Results from these studies will be utilized to better understand the physiology of the sensitization of the pituitary gland to GnRH. This information will be useful in an understanding of the normal changes in sensitivity of this gland to GnRH as well as provide information which can be used in the design of protocols for administration of GnRH-analogs in the treatment of several diseases.
| Vizcarra, J A; Wettemann, R P; Braden, T D et al. (1997) Effect of gonadotropin-releasing hormone (GnRH) pulse frequency on serum and pituitary concentrations of luteinizing hormone and follicle-stimulating hormone, GnRH receptors, and messenger ribonucleic acid for gonadotropin subunits in cows. Endocrinology 138:594-601 |
