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


METHODS
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 (betaCGRP: premenopause Delta cycle threshold [Ct], 31.07 +/- 0.28 vs postmenopause DeltaCt, 30.35 +/- 0.17, P = 0.035; ADM: premenopause subcutaneous fat DeltaCt, 12.41 +/- 0.2 vs postmenopause subcutaneous fat DeltaCt, 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.
Gupta
Pratima
P
Women's Unit, Solihull Hospital and University of Birmingham, Heart of England NHS Foundation Trust, Lode Lane Solihull, West Midlands, UK. guptap@tiscali.co.uk
Harte
Alison L
AL
da Silva
Nancy F
NF
Khan
Hassan
H
Barnett
Anthony H
AH
Kumar
Sudhesh
S
Sturdee
David W
DW
McTernan
Philip G
PG
D000273:Adipose Tissue / Q000378:metabolism*; D053607:Adrenomedullin / Q000378:metabolism*; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D016022:Case-Control Studies; D017931:DNA Primers; D020847:Estrogen Receptor Modulators / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D020847:Estrogen Receptor Modulators; D011506:Proteins; D012333:RNA, Messenger; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide