Prevention by 17beta-estradiol and progesterone of calcitonin gene-related peptide-induced elevation of skin temperature in castrated male rats.
OBJECTIVE
To clarify the relationship between calcitonin gene-related peptide (CGRP) and ovarian hormones (17beta-estradiol and progesterone) in hot flashes in men who undergo androgen deprivation therapy for prostate cancer, we studied the effects of ovarian hormones on CGRP-induced elevation of skin temperature in castrated male rats. The results were compared with those from rats treated with testosterone replacement.


METHODS
Adult male rats were castrated by either a single injection of gonadotropin-releasing hormone analogue (Leuplin, 1.0 mg/kg, subcutaneously) or bilateral orchiectomy. The castrated animals were subcutaneously injected daily for 14 days with ovarian hormones, testosterone, or olive oil as the vehicle. On the day after the final administration of the drug, the changes in skin temperature induced by exogenous CGRP (10 mug/kg intravenously), serum testosterone concentration, and prostate weight were measured.


RESULTS
The CGRP-induced elevation of skin temperature was significantly greater in the castrated rats than in the sham-treated rats. This potentiation was significantly inhibited by treatment with ovarian hormones, as well as by testosterone replacement. The testosterone replacement restored decreases in both the serum testosterone level and the prostate weight due to castration; the treatment with ovarian hormones did not affect them.


CONCLUSIONS
17beta-Estradiol and progesterone, which do not confer testosterone activity on serum, may be useful for the treatment of hot flashes in patients for whom testosterone replacement therapy is contraindicated, such as those with prostate carcinoma. In addition, we suggest that CGRP is closely involved in the amelioration of hot flashes by ovarian hormones in men who undergo androgen deprivation therapy.
Yuzurihara
Mitsutoshi
M
Medicinal Evaluation Laboratory, Tsumura & Company, Inashiki-gun, Ibaraki, Japan.
Ikarashi
Yasushi
Y
Noguchi
Masamichi
M
Kase
Yoshio
Y
Takeda
Shuichi
S
Aburada
Masaki
M
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002369:Castration; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009929:Organ Size; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D011467:Prostate / Q000187:drug effects; D051381:Rats; D012881:Skin Temperature / Q000187:drug effects*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide