Calcitonin Gene Related Peptide (CGRP)II mRNA in human subcutaneous adipose tissue is altered by menopausal status
P Gupta1,2, AL Harte1, MJ Hill1, AH Barnett3, DW Sturdee2, S Kumar1 & PG McTernan1
CGRP, a potent vasodilator, is elevated in the intense periods during menopausal hot flushes and presently represents a candidate mediator of vasomotor symptoms. However due to the short half-life of CGRP, the local paracrine effects may be more important than systemic effects. These local paracrine effects may be mediated in conjunction with adipose tissue, due to close physical proximity with the vasculature; as well as altered oestrogen metabolism following menopause. Therefore this study, with LREC approval, examined: 1) whether CGRP mRNA and protein were expressed in adipose tissue and 2) whether oestrogen deficiency after menopause affected CGRP expression in tissue and systemically. Fasted blood samples were collected from pre-menopausal (Pre n=17: FHS less than 20IU/L, oestradiol 432.81plus/minus95.72 (mean plus/minus SEM) pmol/L) and post-menopausal (Post n=17: FSH greater than 20 IU/L, oestradiol 78.4plus/minus19.95pmol/L) women and analysed for CGRP levels by ELISA. Adipose tissue biopsies (Pre: n=9, Post: n=11) were also collected. CGRP mRNA expression (CGRP-I, CGRP-II) was determined by real time PCR and protein expression by western blot. Our studies determined CGRP-I and CGRP-II mRNA was expressed in both abdominal subcutaneous (AbSc) and omental (Om) human adipose tissue, with low mRNA expression of CGRP I (Pre: deltaCT=29.9plus/minus1.6 (mean±SD) Vs Post: deltaCT=28.83plus/minus0.7). Further in postmenopausal women CGRP-II mRNA levels were raised in AbSc fat when compared to pre-menopausal women (Pre: deltaCT=27.94plus/minus0.54 Vs Post: deltaCT=28.83plus/minus0.8, p=0.012). CGRP protein expression was noted in both AbSc and Om adipose tissue. As anticipated, serum CGRP was detected in both cohorts (Pre: 49.36plus/minus20.49pg/L; Post: 100.0plus/minus50.7pg/L; P=NS), with no significant difference observed. In summary, adipose tissue expresses CRGP. In addition, changing menopausal status alters mRNA expression of CGRP II in Abd Sc fat whilst serum levels remain unchanged. In conclusion, these data suggest adipose tissue as an important site for CGRP production and potential mediator in the pathophysiology of menopausal vasomotor symptoms.