Release of prostaglandins from the uterus

There is much evidence for the existence of a luteolytic hormone (luteolysin) secreted by the uterus towards the end of the oe3trous cycle or pseudopregnancy in several mammalian species. Its chemical identity is unknown. Distension of the uterus by the insertion of a foreign body or the systemic administration of oestrogen causes early regression of the corpora lutea due to the premature release of this hormone.There is much evidence for the existence of a luteolytic hormone (luteolysin) secreted by the uterus towards the end of the oestrous cycle or pseudopregnancy in several mammalian species. Its chemical identity is unknown. Distension of the uterus by the insertion of a foreign body or the systemic administration of oestrogen causes early regression of the corpora lutea due to the premature release of this hormone.Prostaglandin F₂α. possesses potent luteolytic activity in all of the species so far tested. Consequently experiments have been performed to investigate whether the uterine luteolytic hormone could be this prostaglandin.Distension of the guinea-pig uterus in vitro and the sys tonic administration of oestrogen to guinea-pigs were found to release prostaglandin F₂α from the uterus. The analysis of uterine venous blood samples taken from cycling sheep and guineapigs showed prostaglandin F₂ α to be present in levels higher at the end of the oestrous cycle than at times earlier. Also the uterine venous blood of guineapigs contained a high level of prostaglandin E₂ at the end of the cycle.In sheep with an ovary autotransplanted to the neck, cyclic activity ceases. The fluid which often accumulates in the uterus of such sheep has been analysed and was found to contain large amounts of prostaglandin F₂ α. In addition, prostaglandin F-like activity was detected in the uterine venous blood but not the carotid arterial blood of one of these sheep. The results of these findings are discussed.Prostaglandins F₂α and E₂ were present in guinea-pig uterine tissue in small amounts at the end of the oestrous cycle. Guinea-pig uteri taken on selected days throughout the cycle were found capable of biosynthesising prostaglandins F₂ α and E₂ from endogenous precursors during, incubation in vitro. On any one day, 4 to 5 times more prostaglandin F₂α than E₂ was produced, with greater amounts of each being formed nearer to the end of the oestrous cycle. Indomethacin inhibited this synthesis of prostaglandins.The results obtained in this work support the hypothesis that the uterine luteolytic hormone (luteolysin) is prostaglandin F₂α. This view is discussed in relation to connected findings and observations reported by other workers

The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea-pig uterus

1. This study has investigated the effects adenosine 5′-triphosphate (ATP), analogues of ATP, uridine 5′-triphosphate (UTP) and adenosine on prostaglandin output from the guinea-pig uterus superfused in vitro, and from guinea-pig endometrium and myometrium cultured for 24 h. 2. ATP, 2-methylthio ATP and adenosine increased the outputs of prostaglandin F(2α) (PGF(2α)) and 6-keto-PGF(1α) (reflecting PGI(2) production), and UTP increased the output of PGF(2α) from the superfused guinea-pig uterus. These findings support the hypothesis that the contractile effects of ATP, 2-methylthio ATP, UTP and adenosine are mediated by prostaglandins. 3. Suramin (a P2 receptor antagonist) and 8-sulphophenyltheophylline (an A receptor antagonist) blocked the stimulatory actions of ATP and adenosine, respectively, on PGF(2α) output, suggesting that ATP acts on P2 receptors (probably of the P2Y type) and adenosine acts on A receptors in the guinea-pig uterus to increase PGF(2α) production. 4. ATP, 2-methylthio ATP, α,β-methylene ATP, β,γ-methylene ATP, UTP and adenosine increased the output of PGF(2α) from guinea-pig endometrium and myometrium after 24 h of culture, with a greater stimulatory effect being exerted on the endometrium than on the myometrium. Little or no stimulatory effect was seen after 2 and 8 h of culture. In addition the effects of ATP, ATP analogues, UTP and adenosine on the outputs of PGE(2) and 6-keto-PGF(1α) from cultured endometrium and myometrium were more variable, with both stimulation and inhibition being observed. 5. The stimulatory effects of ATP and adenosine on PGF(2α) output from the endometrium and myometrium were associated with an increase in the prostaglandin synthesizing capacity of both tissues, due probably to an increase in the amount of prostaglandin H synthase present