The growth hormone (gh)-releasing hormone (ghrh)- gh-somatomedin axis: Evidence for rapid inhibition of ghrh-elicited gh release by insulin-like growth factors i and ii

Gian Paolo Ceda, Robert G. Davis, Ron G. Rosenfeld, Andrew R. Hoffman

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Hypothalamic-pituitary-end-organ axes are frequently controlled by long loop negative feedback homeostatic mechanisms. Insulin-like growth factor I (IGF-I), IGF-II, and insulin receptors have recently been described in normal and neoplastic rat and acromegalic human pituitary cells, a finding which suggests the possibility that somatomedins might exert feedback at the level of the anterior pituitary. To study the kinetics of this feedback response, we used perifused dispersed rat anterior pituitary cells to learn if somatomedins or insulin could inhibit GH-releasing hormone (GHRH)-stimulated GH secretion. Cells were exposed to hourly boluses of 1 nM GHRH with or without varying doses of IGF or insulin. IGF-I inhibited GHRHelicited GH release with an IC5o of 6.5 nM; maximal inhibition (-67%) was achieved with 10 nM IGF-I. IGF-II was a less potent hormone, with 10 nM inhibiting about 30% of GHRH-stimulated GH release. Slight inhibition of stimulated GH release (%) was seen when cells were treated with insulin, but only when doses of insulin of 10 nM or more were used. In conclusion, 1) nanomolar concentrations of IGF-I and IGF-II inhibited GHRH-elicited GH release from perifused rat pituitary cells in a dose-dependent manner; and 2) insulin was not an effective inhibitor of stimulated GH release at physiological peptide concentrations. In conjunction with our previous findings that the concentrations of IGF-I and IGF-II receptors greatly exceed that of insulin receptors on normal rat pituitary cells, we hypothesize that the GH-inhibiting action of high dose insulin is mediated through an IGF receptor.

Original languageEnglish (US)
Pages (from-to)1658-1662
Number of pages5
JournalEndocrinology
Volume120
Issue number4
DOIs
StatePublished - Apr 1987

ASJC Scopus subject areas

  • Endocrinology

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