A potential role for endothelin-1 in human placental growth: Interactions with the insulin-like growth factor family of peptides

Michael E. Fant, Lydia Nanu, R. Ann Word

Research output: Contribution to journalArticle

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Abstract

Endothelin-1 (Et-1) stimulated DNA synthesis in placental fibroblasts in a dose-dependent manner, as measured by [3H]thymidine incorporation (ED50, 0.2-0.3 ng/mL). Insulin-like growth factor-I (IGF-I) interacted synergistically with Et-1 to potentiate the stimulation of DNA synthesis. Additionally, Et-1 stimulated the turnover of phosphoinositides in a time- and concentration-dependent manner (ED60, 1 ng/mL), as measured by a 2- to 3-fold increase in the total accumulation of [3H]inositol phosphates. This was accompanied by a 2- to 3-fold rise in intracellular calcium, as measured by fura-2 fluorescence. IGF-I, however, had no potentiating effect on Et-1-stimulated phosphoinositide turnover or increase in cytosolic Ca2+. The ability of Et-1 to stimulate the production of IGF-II and IGFBPs by placental fibroblasts was then studied. Western ligand blot analysis using an [125I]IGF-II probe revealed the presence of six major binding proteins corresponding to 42, 38, 35, 32, 31, and 24 kilodaltons. Et-1 (50 ng/mL) stimulated all binding fractions concordantly. This was accompanied by a similar increase in immunoreactive IGF-II secretion, as assessed by a specific RIA. No increase in immunoreactive IGF-I was observed. The ability of the placenta to produce Et-1 was examined by Northern blot analysis. Placentae at 14 and 17 weeks gestation expressed small amounts Et-1 mRNA, whereas significantly higher levels of mRNA were expressed at term. These data suggest that the human placenta produces Et-1 in a developmentally regulated manner that may act via paracrine and/or autocrine mechanisms to regulate placental growth.

Original languageEnglish (US)
Pages (from-to)1158-1163
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume74
Issue number5
StatePublished - May 1992

Fingerprint

Endothelin-1
Somatomedins
Peptides
Growth
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Placenta
Fibroblasts
Phosphatidylinositols
Insulin-Like Growth Factor Binding Proteins
Messenger RNA
Inositol Phosphates
Fura-2
DNA
Northern Blotting
Thymidine
Carrier Proteins
Fluorescence
Western Blotting
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

A potential role for endothelin-1 in human placental growth : Interactions with the insulin-like growth factor family of peptides. / Fant, Michael E.; Nanu, Lydia; Word, R. Ann.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 74, No. 5, 05.1992, p. 1158-1163.

Research output: Contribution to journalArticle

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