Peripheral estrogen receptor-α selectively modulates the waveform of GH secretory bursts in healthy women

Johannes D. Veldhuis, Daniel M. Keenan, Cyril Y. Bowers

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)R1514-R1521
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 2007

Keywords

  • Female
  • Ghrelin
  • Growth hormone releasing hormone
  • Human
  • Secretagogues
  • Somatostatin
  • Somatotropin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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