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Autocrine Prolactin Inhibits Human Uterine Decidualization: A Novel Role for Prolactin¹

Division of Endocrinology,³ Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039 Université Paris Descartes,⁴ Faculté de Médecine René Descartes 5 site Necker, 75015 Paris, France INSERM,⁵ Unit 808, Laboratory of PRL, GH and Tumors, 75730 Paris Cedex 15, France

ABSTRACT

Human prolactin (PRL) and its receptor (PRLR) are markedly induced during human uterine decidualization, and large amounts of PRL are released by decidual cells as differentiation progresses. However, the role of PRL in decidualization is unknown. In order to determine whether PRL plays an autocrine role in decidualization, human uterine fibroblast cells that were decidualized in vitro with medroxyprogestrerone acetate (1 µM), estradiol (10 nM), and prostaglandin E₂ (1 µM) were exposed to exogenous PRL and/or the pure PRLR antagonist delta1–9-G129R-PRL. As measured by quantitative PCR, cells that were decidualized in the presence of exogenous PRL (0.25–2 µg/ml) expressed significantly lower levels of mRNA for the genes that encode insulin-like growth factor binding protein 1 (IGFBP1), left-right determination factor 2 (LEFTY2), PRL, decorin (DCN), and laminin alpha 1 (LAMA1), all of which are known to be induced during decidualization. These effects were blocked when the cells were exposed simultaneously to PRL and the PRLR antagonist, which confirms the specific inhibitory action of PRL on the expression of decidualization markers. In addition, cells exposed to the PRLR antagonist alone expressed higher levels of the marker gene mRNAs than cells that were decidualized in control media. Taken together, these results strongly suggest that PRL acts via an autocrine mechanism to regulate negatively the extent of differentiation (decidualization) of human uterine cells.

decidua, prolactin, prolactin receptor

¹Supported by grant HD-15201 from the National Institutes of Health.

Correspondence: ²Stuart Handwerger, Cincinnati Children's Hospital Medical Center, Division of Endocrinology, MLC 7012, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. FAX: 513 636 7486; e-mail: stuart.handwerger{at}cchmc.org

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