Autocrine prolactin inhibits human uterine decidualization: a novel role for prolactin.
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 microM), estradiol (10 nM), and prostaglandin E(2) (1 microM) 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 microg/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.
Eyal
Ori
O
Division of Endocrinology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039, USA.
Jomain
Jean-Baptiste
JB
Kessler
Cherie
C
Goffin
Vincent
V
Handwerger
Stuart
S
D019898:Autocrine Communication / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics; D055458:Left-Right Determination Factors; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D011981:Receptors, Prolactin / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D053222:Fas Ligand Protein; D018970:Insulin-Like Growth Factor Binding Protein 1; C526161:LEFTY1 protein, human; D007797:Laminin; D055458:Left-Right Determination Factors; D011509:Proteoglycans; D011981:Receptors, Prolactin; D016212:Transforming Growth Factor beta; C084098:laminin A; D012313:RNA; D011388:Prolactin; D053148:Caspase 3