Editors' ChoiceEndocrinology

The Yin and Yang of Steroid Hormones in Placental Development

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Science Translational Medicine  08 Dec 2010:
Vol. 2, Issue 61, pp. 61ec190
DOI: 10.1126/scitranslmed.3001990

A healthy pregnancy depends on a healthy placenta, and a healthy placenta is predicated on adequate growth and development of placental cells called trophoblasts. Although several factors influence the proliferation of trophoblasts, the interplay between the steroid hormones aldosterone and cortisol is thought to be crucial for this process in both animals and humans. In fact, abnormalities in placental growth can result in serious complications of pregnancy, such as preeclampsia, in which elevated blood pressure leads to harm for both mother and fetus. In a new study, Gennari-Moser et al. now investigate more closely the yin and yang relationship of aldosterone and cortisol in placental development in rodents and humans.

Aldosterone, which is instrumental in maintaining adequate plasma volume and placental perfusion, increases steadily throughout pregnancy. The stress hormone cortisol, which is associated with impaired placental development, also increases during pregnancy. In fact, in the absence of aldosterone after adrenalectomy (adrenal gland removal) and in the presence of cortisol, ewes develop smaller placentas. In contrast, adrenalectomized ewes given aldosterone supplements with or without cortisol develop normal placentas. Gennari-Moser et al. take these observations further in rodent and human studies in vitro and in vivo. First, they looked at growth of cultured primary human trophoblasts with aldosterone deficiency induced by the drug spironolactone (an aldosterone antagonist) and exposed to an excess of cortisol. They next examined (i) pregnant mice treated with spironolactone for 12 days before measurement of umbilical vein perfusion, (ii) pregnant rats in which they measured serum aldosterone and placental weight at day 18 of gestation, and (iii) pregnant women in whom they measured first-trimester plasma aldosterone levels and placental weight after delivery. They found that proliferation of first-trimester human trophoblasts was stimulated by aldosterone but inhibited by spironolactone and cortisol, all in a dose-dependent fashion. They observed that umbilical vein flow velocity decreased after spironolactone treatment in mice. Furthermore, aldosterone levels were predictive of placental mass in pregnant rats and women.

This study provides an elegant demonstration in the mouse, rat, and human that a delicate balance between aldosterone and cortisol regulates placental development. These findings provide the basis for further examination of this hormonal yin and yang during normal placental development and during aberrant placental development in preeclampsia and other complications of pregnancy.

C. Gennari-Moser et al., Regulation of placental growth by aldosterone and cortisol. Endocrinology 10 November 2010 (10.1210/en.2010-0525). [Abstract]

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