Gian Carlo Di Renzo

Beta-adrenergic stimulation of prostaglandin production by human amnion tissue

Arachidonic acid is released from specific glycerophospholipids in human amnion and is used to synthesize prostaglandins that are involved in parturition. In an investigation of the regulation of prostaglandin production in amnion, the effects of isoproterenol on discs of amnion tissue maintained in vitro were examined. Isoproterenol caused a large but transitory increase in the amount of cyclic AMP in amnion discs and this was accompanied by a sustained stimulation of the release of arachidonic acid (but not palmitic acid or stearic acid) and prostaglandin E2. The dependencies of cyclic AMP accumulation, arachidonic acid mobilization and prostaglandin E2 release on the concentration of isoproterenol were similar, each response was maximal at 10(-6) M isoproterenol and was inhibited by propranolol. Dibutyryl cyclic AMP stimulated the release of prostaglandin E2 from amnion discs. Although prostaglandin E2, when added to amnion discs caused an accumulation of cyclic AMP, it did not appear to mediate isoproterenol-induced accumulation of cyclic AMP since the latter effect was insensitive to indomethacin in concentrations at which prostaglandin production was inhibited greatly. These data support the proposition that catecholamines, found in increasing amounts in amniotic fluid during late gestation, may be regulators of prostaglandin production by the amnion.

The identification and characterization of β-adrenergic receptors in human amnion tissue

With the use of [125I]iodocyanopindolol as a beta-receptor ligand, beta-receptors were identified and characterized in human amnion tissue. [125I]lodocyanopindolol was found to bind to a total particulate fraction prepared from amnion tissue obtained at term. At low concentrations of [125I]iodocyanopindolol, more than 80% of total [125I]iodocyanopindolol bound was at specific high-affinity sites and could be displaced by an excess of (+/-)-propranolol. The Kd and Bmax for binding of [125I]iodocyanopindolol to amnion beta-receptors were 10.1 +/- 1.1 pM and 46.8 +/- 3.2 fmol/mg protein, respectively. Analysis of the competition for binding to amnion beta-receptors between [125I]iodocyanopindolol and ligands that discriminated between beta 1- and beta 2-receptors revealed that the beta-receptors of human amnion were almost entirely of the beta 2-subtype. The density of beta-receptors found in the amnion at term was approximately three times that found early in the second trimester of gestation. The beta-receptors in human amnion appear to be functional since the in vitro exposure of amnion tissue pieces to isoproterenol (10(-5)M), resulted in a fivefold increase in the intracellular concentration of cyclic adenosine monophosphate. The presence of beta-receptors in the amnion is in keeping with the proposed importance of the catecholamines found in amniotic fluid in the regulation of prostaglandin production by the amnion.

Preterm Birth as a Syndrome

Accumulating observations now indicate that preterm labor, preterm premature rupture of membranes (P-PROM), pre-eclampsia, small for gestational age (SGA), large for gestational age (LGA), recurrent miscarriage, and many other conditions that we deal with in clinical practice are not discrete entities, but are syndromes with more than one cause the so-called great obstetrical syndromes [1].

Effects of corticosteroids on fetal lung maturation

Several investigations and controlled trials have shown that antenatal administration of corticosteroids leads to a significant reduction in the occurrence of respiratory distress syndrome (RDS) and to an overall decrease in neonatal mortality among prematurely delivered infants [1,2]. The effects of corticosteroids on the fetal lung are multilayered and affect a number of aspects of lung maturation. In order to elucidate the mechanisms by which corticosteroids enhance fetal lung maturation, we examined the effects of antenatal administration of betamethasone on different properties of lungs from prematurely delivered rabbit neonates.