Gonadotropin-releasing hormone: molecular and cell biology, physiology, and clinical applications

Fed Proc. 1984 Jun;43(9):2351-61.

Abstract

The observations in recent years that gonadotropin-releasing hormone ( pyroGlu1 -His2-Trp3- Ser4 -Tyr5- Gly6 -Leu7-Arg8-Pro9- G ly10NH2 [GnRH]) has considerable clinical efficacy as a contraceptive, an ovulation-inducing agent, and a drug that is useful in the therapy of a number of diseases are owed in no small part to advances that have been made in the basic molecular biology and physiology of this peptide. It is reasonable then that this symposium should be broken down into three separate yet integrated areas: 1) the molecular and cellular biology of GnRH, 2) the physiology of GnRH, and 3) the clinical efficacy of this compound. A number of recent advances have helped the progress of work in all three of these areas. The observation that substitution of a D-amino acid in the sixth amino acid position leads to considerable metabolic stability and reduced degradation of releasing hormone analogs has been especially useful. In addition, the observation that the further derivatization of such substituted compounds by deletion of the 10th amino acid and addition of an ethylamide group to Pro9 has resulted in compounds with a markedly increased ability to bind to the receptor. These compounds have been useful clinically and have allowed development of radioligand assays to be used in animal studies and in vitro. The availability of a large number of agonists and antagonists has allowed formulation of molecular models for GnRH and resulted in development of clinically useful compounds. In a short paper of this nature we cannot hope to provide an encyclopedic review; rather we hope to provide an overview and offer references to the literature for those who wish a more in-depth treatment.

Publication types

  • Review

MeSH terms

  • Aging
  • Androgens / physiology
  • Animals
  • Calcium / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Estrogens / physiology
  • Feedback
  • Female
  • Follicle Stimulating Hormone / metabolism
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Gonadotropin-Releasing Hormone / pharmacology
  • Gonadotropin-Releasing Hormone / physiology*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Hypothalamus / physiology
  • Infertility / drug therapy
  • Insulin / physiology
  • Luteinizing Hormone / metabolism
  • Macromolecular Substances
  • Male
  • Ovary / drug effects
  • Pituitary Gland / physiology
  • Progestins / physiology
  • Rats
  • Receptors, Cell Surface / physiology
  • Receptors, LHRH
  • Reproduction / drug effects
  • Sex
  • Testis / drug effects

Substances

  • Androgens
  • Estrogens
  • Insulin
  • Macromolecular Substances
  • Progestins
  • Receptors, Cell Surface
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Calcium