Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status

Pratima Gupta, AL Harte, NF da Silva, H Khan, AH Barnett, S Kumar, David Sturdee, PG McTernan

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Objective: Calcitonin gene-related peptide (CGRP) is a vasoactive, proinflammatory neuropeptide implicated in the pathogenesis of cardiovascular disease. Elevated CGRP levels during hot flushes and pregnancy suggest that reproductive hormones may influence CGRP secretion. CGRP and the related protein adrenomedullin (ADM) may function through adipose tissue-mediated effects, since adipose tissue is an important site of cytokine production and the main site for estrogen production after menopause. This study examined mRNA and protein expression of CGRP, ADM, and the receptor activity-modifying proteins and the effects of menopausal status in human adipose tissue. Design: Protein/mRNA levels were determined in adipose tissue biopsy samples collected from premenopausal (n = 22: follicle-stimulating hormone, <20 IU/L; estradiol [mean +/- SEM], 434.5 +/- 87.81 pmol/L) and postmenopausal (n = 25: follicle-stimulating hormone, > 20 IU/L; estradiol, 43.4 +/- 6.95 pmol/L) women. Results: Our studies determined that CGRP, ADM, and receptor activity-modifying proteins were expressed in abdominal fat, adipocytes, and preadipocytes. CGRP and ADM mRNA levels were increased in abdominal subcutaneous fat in postmenopausal women compared with premenopausal women (beta CGRP: premenopause A cycle threshold [Ct], 31.07 +/- 0.28 vs postmenopause Delta Ct, 30.35 +/- 0.17, P = 0.035; ADM: premenopause subcutaneous fat Delta Ct, 12.41 +/- 0.2 vs postmenopause subcutaneous fat Delta Ct, 11.55 +/- 0.14, P <0.001) with CGRP differentially expressed in subcutaneous and omental depots. CGRP protein expression was higher in postmenopausal women (P <0.05) in both fat depots. Conclusions: Our findings suggest that adipose tissue represents an important site for CGRP and ADM production and that menopause status alters their expression in abdominal fat. This offers a potential mechanism to explain the role of CGRP in menopausal vasomotor symptoms and the increased risk of cardiovascular disease in postmenopausal women.
    Original languageEnglish
    Pages (from-to)1031-1038
    Number of pages8
    JournalMenopause
    Volume14
    Issue number6
    DOIs
    Publication statusPublished - 1 Nov 2007

    Keywords

    • adipose tissue
    • calcitonin gene-related peptide
    • menopause
    • adrenomedullin
    • receptor-modifying proteins

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