Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta.
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 mumol/l final concentration in all cases), and were stimulated with terbutaline, a beta-adrenergic agonist, (0.1 mmol/l) or angiotensin II (1 mumol/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.
Rivera
J
J
Department of Obstetrics and Gynecology, Facultad de Medicina, Universidad de Valencia, Spain.
Lopez Bernal
A
A
Cano
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D002852:Chromatography, Ion Exchange; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007743:Labor, Obstetric; D007773:Lactates / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D013726:Terbutaline / Q000494:pharmacology*; D014343:Trypan Blue
D007295:Inositol Phosphates; D007773:Lactates; D000804:Angiotensin II; D011374:Progesterone; D004958:Estradiol; D000242:Cyclic AMP; D014343:Trypan Blue; D013726:Terbutaline