adrenomedullin and Hot-Flashes

Administration of calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) can cause facial flushing, suggesting that the peptides may be important in hot flushes experienced particularly by post-menopausal women. Five studies have measured plasma CGRP concentrations in post-menopausal women who suffer from flushes; all demonstrated elevations of between 170% and 320% over control. Three of the studies showed a temporal relationship between flushes and CGRP elevation. A further study has shown that CGRP is elevated in the urine of women who suffer from flushes. Only a single study has investigated flushes in pre-menopausal women; no elevation of CGRP was observed. Flushes are also experienced by men undergoing androgen deprivation therapy. Whilst one study failed to find any increase in CGRP in the urine of these individuals, a small study has identified an increase in plasma CGRP. No studies have investigated plasma AM or the related peptide, intermedin/AM2. Overall, there is good evidence to show that flushes in post-menopausal women are accompanied by an increase in CGRP. CGRP could act centrally on the thermoregulatory centre of the hypothalamus as well as peripherally to cause vasodilation and sweating. However, it remains to be demonstrated that the elevated CGRP causes flushes. Recently developed CGRP antagonists provide an opportunity to test this hypothesis. If they are successful, they may represent a useful alternative to oestrogen replacement therapy.

Topics: Adrenomedullin; Calcitonin Gene-Related Peptide; Female; Hot Flashes; Humans; Male; Postmenopause

To assess the involvement of calcitonin gene-related peptide (CGRP) in the occurrence of hot flashes in men after castration for treatment of prostate cancer, we investigated the effects of CGRP on skin temperature in surgically and medically castrated male rats.. Changes in skin temperature of the hind paws after intravenous injection of 10 microg/kg of CGRP and CGRP family peptides (adrenomedullin and amylin) were measured at 5-minute intervals for 120 minutes, 3 weeks after bilateral orchiectomy or 2 weeks after subcutaneous injection of a gonadotropin-releasing hormone analogue (1.0 mg/kg Leuplin) in male rats. Antagonism with CGRP8-37 (1000 microg/kg intravenously), a CGRP1 receptor antagonist, to the CGRP-induced response was examined by injecting it 10 minutes before injection of CGRP. The effect of testosterone replacement on castration was evaluated in each castrated rat by the administration of testosterone (1.0 mg/kg subcutaneously once a day) for 14 days before the day of the temperature analysis.. CGRP, but not adrenomedullin and amylin, elevated the skin temperature in surgical or medical castration-induced testosterone-deficient rats more than in the sham-treated rats. The difference was statistically significant. The CGRP-induced potentiation in the castrated rats was inhibited by pretreating with CGRP8-37 or by supplying testosterone.. CGRP is the most potent peptide in a family that elevates the skin temperature in male rats. The elevation of the skin temperature was more affected by the testosterone deficiency resulting from castration. These results suggest that CGRP is involved in the mechanism underlying hot flashes in men.

Topics: Adrenomedullin; Amyloid; Animals; Calcitonin Gene-Related Peptide; Gonadotropin-Releasing Hormone; Hindlimb; Hormone Antagonists; Hot Flashes; Injections, Intravenous; Islet Amyloid Polypeptide; Leuprolide; Male; Orchiectomy; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley; Receptors, Calcitonin Gene-Related Peptide; Skin Temperature; Testosterone