Journal of Clinical Endocrinology & Metabolism, Vol 80, 1233-1237, Copyright © 1995 by Endocrine Society

ARTICLES

Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation

MK Kalenga, M De Gasparo, K Thomas and R De Hertogh
Department of Obstetrics and Gynecology, University of Louvain, Brussels, Belgium.

A complete renin-angiotensin system has been shown to be present in human placenta, but its physiological role is poorly known. To investigate the implication of this system in the regulation of steroid hormone secretion, we studied the effect of angiotensin-II on the release of estradiol and progesterone from human placental explants. Our experiments showed that angiotensin-II stimulated estradiol secretion from term placental explants in a dose- and time-dependent fashion, although progesterone release was unaffected. Estradiol release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1 receptor antagonist losartan in a dose-dependent manner, suggesting the involvement of the AT1 receptor subtype in the process. On the contrary, the angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2 receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of steroid hormones in the placental tissues incubated for 12 h showed that angiotensin-II increased estradiol production by 34% compared with the unstimulated explants, whereas the total levels of the estrogen precursor androstenedione and testosterone were decreased by 30-45% in the presence of the peptide, suggesting a stimulatory effect on the aromatization step. This hypothesis was reinforced by the absence of effect of angiotensin-II on both estradiol and testosterone concentrations in the placental explants pretreated with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone synthesis was not affected by angiotensin-II. The present study indicates that angiotensin-II induces the secretion of estradiol from human placenta through the angiotensin AT1 receptor subtype activation, and this effect seems to be linked to the stimulation of local androgen aromatization.

This article has been cited by other articles:

				F. Liang, A. M. Kapoun, A. Lam, D. L. Damm, D. Quan, M. O'Connell, and A. A. Protter B-Type Natriuretic Peptide Inhibited Angiotensin II-Stimulated Cholesterol Biosynthesis, Cholesterol Transfer, and Steroidogenesis in Primary Human Adrenocortical Cells Endocrinology, August 1, 2007; 148(8): 3722 - 3729. [Abstract] [Full Text] [PDF]

				K. Ino, C. Uehara, F. Kikkawa, H. Kajiyama, K. Shibata, T. Suzuki, E. E. Khin, M. Ito, M. Takeuchi, A. Itakura, et al. Enhancement of Aminopeptidase A Expression during Angiotensin II-Induced Choriocarcinoma Cell Proliferation through AT1 Receptor Involving Protein Kinase C- and Mitogen-Activated Protein Kinase-Dependent Signaling Pathway J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3973 - 3982. [Abstract] [Full Text] [PDF]

				K.H. Schauser, A.H. Nielsen, H. Winther, V. Dantzer, and K. Poulsen Autoradiographic Localization and Characterization of Angiotensin II Receptors in the Bovine Placenta and Fetal Membranes Biol Reprod, July 1, 1998; 59(3): 684 - 692. [Abstract] [Full Text]

				A. Petit, P. Geoffroy, and S. Belisle Expression of Angiotensin II Type-I Receptor and Phospholipase C-Linked G{alpha}q/11 Protein in the Human Placenta Reproductive Sciences, November 1, 1996; 3(6): 316 - 321. [Abstract] [PDF]

				T. L. Goodfriend, M. E. Elliott, and K. J. Catt Angiotensin Receptors and Their Antagonists N. Engl. J. Med., June 20, 1996; 334(25): 1649 - 1655. [Full Text] [PDF]