The role of gonadotropin releasing hormone in normal and pathologic endocrine processes

Abstract

Gonadotropin releasing hormone is the hypothalamic hormone that activates pituitary gonadotropin production and, ultimately, determines reproductive competence. This review will highlight advances in the basic biology of the gonadotropin releasing hormone neuron that give insight into disorders of pubertal development, and clinical studies with gonadotropin releasing hormone analogs in infertility and prostate cancer treatment. Factors that control gonadotropin releasing hormone neuronal migration such as fibroblast growth factor receptor-1 and others that modulate secretion at puberty including kisspeptin/G-protein-coupled receptor 54 have been identified. Mutations in these pathways cause disorders during puberty. Clinical trials have defined the utility of gonadotropin releasing hormone agonists and antagonists for ovulation induction, and the effects of long-term administration for prostate cancer. Research into the role of the fibroblast growth factor receptor-1 and kisspeptin/G-protein-coupled receptor 54 pathways in gonadotropin releasing hormone neuronal development may identify the molecular defects in idiopathic hypogonadotropic hypogonadism and refine our understanding of normal negative and positive feedback by sex steroids. Clarification of the advantages and disadvantages of gonadotropin releasing hormone analog use in ovulation induction may improve the cost and success of infertility treatment. Insight into long-term effects of gonadotropin releasing hormone analogs in prostate cancer may lead to directed therapies to combat these consequences. Together these studies outline effects of modulation of gonadotropin releasing hormone in normal and pathophysiologic states.