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Regulation of IGF bioavailability in pregnancy

Gibson, J M; Aplin, J D; White, A; Westwood, M

Molecular Human Reproduction. 2001;7(1):79-87.

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Abstract

During pregnancy, insulin-like growth factors (IGFs) are important for growth of fetal and maternal tissues. One of the IGF binding proteins, IGFBP-1, is thought to regulate their activity within the local environment of the placenta. IGFBP-1 usually exists as a phosphorylated, high affinity species, which sequesters IGFs, thereby inhibiting their actions. This study has investigated the mechanisms that release IGF from IGFBP-1 at the maternal-fetal interface. Under basal conditions, human decidualized endometrium produces both non-phosphorylated (np) and phosphorylated (p) isoforms of IGFBP-1; however, in the presence of IGF-II, which is a trophoblast secretory product, npIGPBP-1 was preferentially produced, Furthermore, we found that trophoblast; presumably via placental alkaline phosphatase, can de-phosphorylate pIGFBP-1, Since npIGFBP-1 has decreased affinity for IGF-I, these effects should enhance IGF-I bioavailability, In addition, we found that decidual cells produce a protease, which cleaves IGFBP-1, but only when it is non-phosphorylated; [I-125]-npIGFBP-1 is proteolysed into 14 and 17 kDa fragments which have markedly reduced affinity for IGF, We therefore propose paracrine modulation of IGFBP-1 at the maternal-fetal interface involving a multi-step process of de-phosphorylation and proteolysis; this will result in enhanced IGF bioavailability and is likely to represent an important mechanism for controlling fetal and maternal tissue growth.

Bibliographic metadata

Type of resource:
Content type:
Published date:
Volume:
7
Issue:
1
Start page:
79
End page:
87
Total:
9
Pagination:
79-87
Digital Object Identifier:
10.1093/molehr/7.1.79
ISI Accession Number:
ISI:000166460800012
Related website(s):
  • Related website <Go to ISI>://000166460800012
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:151223
Created by:
Gibson, Martin
Created:
15th January, 2012, 15:04:10
Last modified by:
Gibson, Martin
Last modified:
1st February, 2013, 19:48:42