Tocolytic effects of formoterol are associated with local change in the progesterone/estradiol ratio.
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.


METHODS
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.


CONCLUSIONS
These findings indicate that tocolytic effects of formoterol may be associated with suppression of uterine activity due to modulation of hormone secretion.
Shinkai
Norihiro
N
Daiichi Pharmaceutical Co Ltd, 8-1 Minamisakae-cho, Kasukabe, Saitama 344-0067, Japan. shinkai@sdsk.co.jp
Sasaki
Hiroyuki
H
Okumura
Yutaka
Y
Saito
Hideo
H
Takasuna
Kiyoshi
K
Takayama
Satoshi
S
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000653:Amniotic Fluid / Q000737:chemistry*; D000818:Animals; D015237:Dinoprost / Q000032:analysis; D004958:Estradiol / Q000008:administration & dosage / Q000032:analysis*; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D000068759:Formoterol Fumarate; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000032:analysis*; D051381:Rats; D015149:Tocolytic Agents / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D015149:Tocolytic Agents; D011374:Progesterone; D004958:Estradiol; D015237:Dinoprost; D020780:Matrix Metalloproteinase 9; D000068759:Formoterol Fumarate