6533b85bfe1ef96bd12ba2b8

RESEARCH PRODUCT

Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta.

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Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3′,5′-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 μmol/l final concentration in all cases), and were stimulated with terbutaline, a β-adrenergic agonist, (0.1 mmol/l) or angiotensin II(1 μmol/l), The cAMP content was measured by a competitive protein binding assay, and the generation of labelled inositol phosphates formation in explants prelabelled with 3H-myo-inositol was measured by anion exchange chromatography. Progesterone increased significantly basal cAMP concentrations in comparison with control or estradiol-treated tissues (169±13, 72±8, and 69±2 pmol/g wet wt tissue, mean±sem, respectively). However, following terbutaline stimulation cAMP levels (mean±sem) increased to similar values under all conditions (182±33, 197±36, and 237±17 pmol/g wet wt tissue for control, estradiol-, and progesterone-treated tissues, respectively). Angiotensin II stimulated inositol phosphates generation in placental explants by an average of fivefold, but this increase was significantly reduced in the presence of progesterone (5.2±0.7, 3.7±0.4, and 2.2±0.3 fold increase vs non-angiotensin-stimulated tissues, for control, estradiol-, and progesterone-treated placenta, mean±sem, respectively). These data suggest that progesterone modulates the formation of second messengers in human placenta at term.