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LRH-1: orphaned, adopted and needed for pregnancy

Nature Medicine volume 19, pages 968–969 (2013)Cite this article

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A new study shows that the orphan nuclear receptor liver receptor homolog 1 (LRH-1) wires the postovulatory rise in progesterone production to progesterone-dependent preparation of the endometrium for pregnancy, a process termed decidualization. Lack of Lrh-1 activity in either the ovary or uterus has catastrophic consequences for reproduction in mice (pages 1061–1066).

Life throws you curve balls. Michael, a nightclub bouncer, thought he could handle a challenge. However, he was left utterly devastated when his partner, Kathryne, miscarried again after ten previous fetal losses and a stillbirth. Like numerous other women, Kathryne was given progesterone supplementation to prevent pregnancy loss1. The rationale for this hormonal intervention seemed sound; after all, progesterone is the overarching regulator of pregnancy. Upon ovulation, progesterone produced by the corpus luteum in the ovary leads to a steep rise in the circulating concentration of this hormone, which in turn renders the endometrium receptive to embryo implantation and drives the differentiation of stromal cells into specialist decidual cells. In pregnancy, progesterone induces uterine quiescence and maintains the decidua throughout gestation. Consequently, micronized progesterone and synthetic derivatives are widely used to increase pregnancy rates after in vitro fertilization treatment and to prevent miscarriage or preterm labor in at-risk women. Clinical studies support the use of progesterone2, although this intervention is often not sufficient to prevent pregnancy loss, as illustrated by Kathryne's case.

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Figure 1: LRH-1 integrates progesterone production in the ovary and actions in the uterus.

Marina Corral Spence

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Authors and Affiliations

  1. Jan J. Brosens, Andrew M. Blanks and Emma S. Lucas are in the Biomedical Research Unit in Reproductive Health, Warwick Medical School, University Hospital Coventry & Warwickshire, Coventry, UK.,

    Jan J Brosens, Andrew M Blanks & Emma S Lucas

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  1. Jan J Brosens
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  2. Andrew M Blanks
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  3. Emma S Lucas
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Correspondence to Jan J Brosens.

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Brosens, J., Blanks, A. & Lucas, E. LRH-1: orphaned, adopted and needed for pregnancy. Nat Med 19, 968–969 (2013). https://doi.org/10.1038/nm.3271

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