Angiotensin-II stimulates estradiol secretion from human placental explants through AT1 receptor activation.
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.
Kalenga
M K
MK
Department of Obstetrics and Gynecology, University of Louvain, Brussels, Belgium.
De Gasparo
M
M
Thomas
K
K
De Hertogh
R
R
D000804:Angiotensin II / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000145:classification / Q000502:physiology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011374:Progesterone; D004958:Estradiol