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

• Published in: Biology of reproduction 2007-05, Vol.76 (5), p.777-783
• Main Authors: Eyal, Ori, Jomain, Jean-Baptiste, Kessler, Cherie, Goffin, Vincent, Handwerger, Stuart
• Format: Article
• Language: English
• Subjects: Autocrine Communication - physiology; Biological and medical sciences; Blotting, Western; Caspase 3 - biosynthesis; Caspase 3 - genetics; Decidua - drug effects; Decidua - physiology; Decorin; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Fas Ligand Protein - biosynthesis; Fas Ligand Protein - genetics; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Humans; Insulin-Like Growth Factor Binding Protein 1 - biosynthesis; Insulin-Like Growth Factor Binding Protein 1 - genetics; Laminin - biosynthesis; Laminin - genetics; Left-Right Determination Factors; Mammalian female genital system; Prolactin - antagonists & inhibitors; Prolactin - pharmacology; Prolactin - physiology; Proteoglycans - biosynthesis; Proteoglycans - genetics; Receptors, Prolactin - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics; Uterus - drug effects; Uterus - physiology; Vertebrates: reproduction
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.106.053058

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.