Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2

Estrogen is the proximate sex steroid sustaining GH secretion throughout th e human life span in both sexes. However, very little is known about the sp ecific neuroendocrine mechanisms by which estrogen activates and maintains CH secretion in the young or aging human. The identification of somatostati n in 1973 as a key negative peptidyl regulator of the GH axis and the disco very of GH-releasing hormone (GHRH) in 1982 as a dominant feedforward agoni st of GH secretion provided an initial basic science foundation for explori ng sex-steroid control of the GH-IGF-1 axis. Although GH-releasing peptides (GHRPs) were first recognized in 1977-1981, subsequent cloning of hypothal amopituitary receptors transducing potent secretagogue actions of GHRPs in 1996 and of an endogenous ligand for this effector pathway in 1999 now exte nd the framework for examining the mechanisms of estrogen-driven GH secreti on in aging, Herein, we review several novel and multifaceted interactions in postmenopausal women between estrogen and GHRP-2, We combine these obser vations into a simplified construct of CH-axis neuroregulation comprising t he somatostatin, GHRH, and GHRP effector pathways, as well as GH and IGF-1 autofeedback. We suggest the thesis that estrogen controls the interfaces a mong these pivotal regulatory peptides in hyposomatotropic postmenopausal i ndividuals.