dinoprost and diethylenetriamine

The present studies were undertaken to determine whether nitric oxide (NO) is involved in the regulation of ovarian progesterone and oestradiol secretion in rats. Immature female Sprague-Dawley rats at 27 days of age were injected s.c. with 4 IU pregnant mare's serum gonadotrophin (PMSG) and were killed 72 h after the injection. The ovaries were collected, weighed and cultured in Dulbecco's modified Eagle's medium containing saline, NO donor, NO synthesis inhibitor or prostaglandin F2 alpha (PGF2 alpha). After 24 h culture, the medium concentrations of progesterone and oestradiol were measured by radioimmunoassay. Results showed that: (i) diethylenetriamine (DETA)/NO (1 x 10(-6), 1 x 10(-5), 1 x 10(-4) M), an NO donor, caused a dose-dependent increase in progesterone synthesis (355 +/- 43, 443 +/- 46, 647 +/- 55 ng/g ovary respectively, P < 0.01) with a concomitant decrease in ovarian oestradiol secretion (408.1 +/- 50.7, 272.9 +/- 28.2, 132.6 +/- 34.6 pg/g ovary respectively, P < 0.01); (ii) neither progesterone nor oestradiol concentrations in the culture medium were altered by DETA without NO; (iii) NG-nitro-l-arginine methyl ester (1 x 10(-4) M), an inhibitor of NO synthesis, did not significantly affect progesterone and oestradiol secretion by rat ovaries; (iv) PGF2 alpha(1 x 10(-6) M) caused a fall in progesterone and oestradiol synthesis; (v) co-incubation with DETA/NO, significantly reversed the PGF2 alpha-induced decrease in progesterone concentrations from 184 +/- 29 to 388 +/- 60 ng/g (P < 0.01), but not that of oestradiol. It can be concluded that NO up-regulates progesterone secretion and down-regulates oestradiol secretion in rat ovaries, and NO can reverse PGF2 alpha-induced inhibition in ovarian progesterone secretion.

Topics: Animals; Dinoprost; Estradiol; Female; Nitric Oxide; Organ Culture Techniques; Ovary; Polyamines; Progesterone; Rats; Rats, Sprague-Dawley

Our purpose was to investigate the roles of nitric oxide and prostaglandins in controlling parturition.. Pregnant rats on day 18 of gestation were injected intraperitoneally with prostaglandin F2 alpha, prostaglandin F2 alpha plus diethylenetriamine-nitric oxide (a donor of nitric oxide), prostaglandin F2 alpha plus diethylenetriamine without nitric oxide, or vehicle. Uterine nitrite production, nitric oxide synthase messenger ribonucleic acid and contractile response in vitro, and serum progesterone levels were measured. The labor and delivery of the rats also were monitored.. Exogenously administered prostaglandin F2 alpha significantly inhibited nitric oxide production by the uterus in a time-dependent manner with maximal effects observed 48 hours after prostaglandin F2 alpha treatment. Messenger ribonucleic acid for inducible nitric oxide synthase but not endothelial nitric oxide synthase messenger ribonucleic acid in the uterus was significantly inhibited by prostaglandin F2 alpha with maximal inhibition at 48 hours after prostaglandin F2 alpha injection. The serum progesterone concentration was substantially reduced by prostaglandin F2 alpha, and this reduction was partially reversed by administration of diethylenetriamine-nitric oxide but not diethylenetriamine without nitric oxide. Prostaglandin F2 alpha caused increases in contractile activity of the uterus in a dose-dependent manner. Diethylenetriamine-nitric oxide (10(-4) mol/L) blocked prostaglandin F2 alpha-induced contractions. Premature parturition was induced within 48 hours after prostaglandin F2 alpha injection in 100% of the animals. Coadministration of diethylenetriamine-nitric oxide completely prevented the preterm labor induced by prostaglandin F2 alpha.. Prostaglandin F2 alpha inhibited inducible nitric oxide synthase messenger ribonucleic acid and subsequent nitric oxide generation in the rat uterus. Nitric oxide can prevent prostaglandin F2 alpha-induced preterm labor, possibly by attenuating the fall in serum progesterone and blocking uterine contractions induced by prostaglandin F2 alpha administration.

Topics: Animals; Dinoprost; Enzyme Inhibitors; Female; Injections, Intraperitoneal; Kinetics; Nitric Oxide; Nitric Oxide Synthase; Obstetric Labor, Premature; Polyamines; Pregnancy; Progesterone; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uterine Contraction; Uterus