Gonadotropin-releasing hormone and its clinical applications
Loucopoulos, A.; Ferin, M.
Obstetrics and Gynecology Annual 13: 275-288
1984
ISSN/ISBN: 0091-3332 PMID: 6326010 Document Number: 404592
Evidence has accumulated that the hypothalamus contains neurohumoral substances which, upon secretion into the hypothalamo-hypophyseal portal circulation, control the release of anterior pituitary hormones. Gonadotropin-releasing hormone (GnRH) is a decapeptide that has been synthesized and used in studies on the way the hypothalamus controls anterior pituitary secretion. Several therapeutic applications for GnRH have also been investigated. The greatest amount of GnRH in the brain is within the hypothalamus where GnRH immunoreactive perikarya are in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly. Two major GnRH pathways control gonadotropin release in the primate: 1 originates in the arcuate nucleus, while the other derives from cell bodies in the anterior hypothalamic region. Hypothalamic GnRH is essential not only for the release but also for the synthesis of both gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Intermittent gonadotropin release is the result of pulsatile activity by the hypothalamus, not of the pituitary gland. Various experiments have been done to modify pulsatile gonadotropin release through endocrine modulation by ovarian steroids. GnRH has been used successfully to stimulate ovulation and spermatogenesis. Advantages of GnRH treatment for hypogonadism include 1) a more physiologic approach, because stimulation of the anterior pituitary gland is intermittent; 2) LH/FSH responses are controlled by endogenous gonadal feedback mechanisms, reducing chance of target organ hyperstimulation; and 3) cost per treatment cycle is lower than that for other therapeutic modalities because GnRH is a simple molecule. Agonists and antagonists resemble each other in their end biologic action, and both classes of GnRH analogs have been used to decrease gonadotropin and gonadal activities.