Estradiol (E2) drives growth hormone (GH) secretion via estrogen receptors (ER) located in the hypothalamus and pituitary gland. ERα is expressed in GH releasing hormone (GHRH) neurons and GH-secreting cells (somatotropes). Moreover, estrogen regulates receptors for somatostatin, GHR peptide (GHRP, ghrelin), and GH itself, while potentiating signaling by IGF-I. Given this complex network, one cannot a priori predict the selective roles of hypothalamic compared with pituitary ER pathways. To make such a distinction, we introduce an investigative model comprising 1) specific ERα blockade with a pure antiestrogen, fulvestrant, that does not penetrate the blood-brain barrier; 2) graded transdermal E2 administration, which doubles GH concentrations in postmenopausal women; 3) stimulation of fasting GH secretion by pairs of GHRH, GHRP-2 (a ghrelin analog), and L-arginine (to putatively limit somatostatin outflow); and 4) implementation of a flexible waveform deconvolution model to estimate the shape of secretory bursts independently of their size. The combined strategy unveiled that 1) E2 prolongs GH secretory bursts via fulvestrant-antagonizable mechanisms; 2) fulvestrant extends GHRH/GHRP-2-stimulated secretory bursts; 3) L-arginine/GHRP-2 stimulation lengthens GH secretory bursts whether or not E2 is present; 4) E2 limits the capability of L-arginine/GHRP-2 to expand GH secretory bursts, and fulvestrant does not inhibit this effect; and 5) E 2 and/or fulvestrant do not alter the time evolution of L-arginine/GHRH-induced GH secretory bursts. The collective data indicate that peripheral ERα-dependent mechanisms determine the shape (waveform) of in vivo GH secretory bursts and that such mechanisms operate with secretagogue selectivity.
|Original language||English (US)|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|State||Published - Oct 2007|
- Growth hormone releasing hormone
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