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Tocolytic effects of formoterol are associated with local change in the progesterone/estradiol ratio
Norihiro Shinkai1, Hiroyuki Sasaki, Yutaka Okumura
1Daiichi Pharmaceutical Co Ltd, 8-1 Minamisakae-cho, Kasukabe, Saitama 344-0067, Japan. shinkai@sdsk.co.jp
Objective:
The aim of the study was to determine whether a beta(2)-adrenoceptor agonist, formoterol, inhibits premature delivery in connection with change in estradiol and progesterone concentrations in the amniotic fluid in ovariectomized rats.
Study Design:
Pregnant rats at the 15th day of gestation were bilaterally ovariectomized and given injection of 17beta-estradiol immediately after the operation and every 24 h. An osmotic pump filled with a solution of formoterol or saline was also implanted subcutaneously into the back of each. The animals were killed by decapitation under light ether anesthesia 18, 36, 54 or 72 h after ovariectomy, and the numbers of undelivered fetuses and newborn were counted. Amniotic fluid was collected 16, 36, and 54 h after ovariectomy.
Results:
Formoterol (0.15 mg/(kg h)) reversed the decline in premature delivered fetuses due to 17beta-estradiol 54 and 72 h after ovariectomy. Although no influence was evident regarding the progesterone and estradiol concentrations in amniotic fluid in ovariectomized rats supplemented with 17beta-estradiol, formoterol significantly inhibited the increment in the estradiol/progesterone ratio as well as the elevation in prostaglandin F2alpha concentration.
Conclusion:
These findings indicate that tocolytic effects of formoterol may be associated with suppression of uterine activity due to modulation of hormone secretion.
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