TY - JOUR
T1 - Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status
AU - Gupta, Pratima
AU - Harte, AL
AU - da Silva, NF
AU - Khan, H
AU - Barnett, AH
AU - Kumar, S
AU - Sturdee, David
AU - McTernan, PG
PY - 2007/11/1
Y1 - 2007/11/1
N2 - 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.
AB - 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.
KW - adipose tissue
KW - calcitonin gene-related peptide
KW - menopause
KW - adrenomedullin
KW - receptor-modifying proteins
U2 - 10.1097/gme.0b013e31803c56b6
DO - 10.1097/gme.0b013e31803c56b6
M3 - Article
C2 - 17572645
SN - 1072-3714
VL - 14
SP - 1031
EP - 1038
JO - Menopause
JF - Menopause
IS - 6
ER -
