Linked Life Data

17686882

Source:http://linkedlifedata.com/resource/pubmed/id/17686882

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-3
pubmed:abstractText
Estradiol (E(2)) drives growth hormone (GH) secretion via estrogen receptors (ER) located in the hypothalamus and pituitary gland. ERalpha 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 ERalpha blockade with a pure antiestrogen, fulvestrant, that does not penetrate the blood-brain barrier; 2) graded transdermal E(2) 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) E(2) 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 E(2) is present; 4) E(2) 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 ERalpha-dependent mechanisms determine the shape (waveform) of in vivo GH secretory bursts and that such mechanisms operate with secretagogue selectivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1514-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Peripheral estrogen receptor-alpha selectively modulates the waveform of GH secretory bursts in healthy women.
pubmed:affiliation
Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Unit, Mayo Clinic, Rochester, MN 55905, USA. Veldhuis.Johannes@mayo.edu
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural