Human chorionic gonadotropin stimulates placental prorenin secretion: evidence for autocrine/paracrine regulation.
Functional regulation of the placental renin-angiotensin system remains incompletely defined. Evidence indicates that synthesis and secretion of prorenin in the placenta and gestational sac decrease with advancing gestational age. Possible explanations for this developmental effect include the regulatory influences by locally released hormones, such as CG. To address this question, the effect of CG on prorenin secretion was evaluated in a human placental explant model. In this study, prorenin concentrations were measured in the media and tissue of cultured explants from term placentas. In addition, the role of cAMP in mediating hormone-regulated prorenin secretion was evaluated. Media and tissue concentrations of prorenin increased (2- and 3-fold, respectively) in a concentration-dependent fashion after 48 h of incubation with CG (0.03-300 IU/ml). Selective inhibition of phosphodiesterases by Ro 20-1724 (type IV) and cilostamide (type III) resulted in a marked potentiation of CG-induced prorenin secretion. Media concentrations of cAMP were also elevated with CG treatment and correlated with prorenin values. Prorenin secretion induced by CG was markedly attenuated by the cAMP-dependent protein kinase inhibitor, H-89. These results indicate that placental prorenin secretion may be locally regulated by CG and mediated by cAMP signal transduction mechanisms.
Downing
G J
GJ
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Maulik
D
D
Poisner
A M
AM
D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009994:Osmolar Concentration; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012083:Renin / Q000378:metabolism*; D013449:Sulfonamides
D006063:Chorionic Gonadotropin; D004792:Enzyme Precursors; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D012083:Renin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide