Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PRL is synthesized by decidualized endometrial stromal cells from the midsecretory phase in a nonconception cycle and throughout pregnancy. The exact role of PRL in the human endometrium remains to be elucidated; however, the pattern of expression supports a role for PRL during implantation and placentation. This study investigated the site and pattern of expression of PRL receptors in the nonpregnant human endometrium. In situ hybridization and immunohistochemistry localized expression of the receptor in the glandular epithelium and a subset of stromal cells of the endometrium. As judged by the intensity of staining, expression of the receptor was dramatically up-regulated during the secretory phase. Expression of the PRL receptor gene in the endometrium from the secretory phase of the menstrual cycle was confirmed by ribonuclease protection assay using 50 micrograms total ribonucleic acid. Phosphorylation of Janus kinase-2 (JAK2), STAT1 (signal transducer and activator of transcription-1), and STAT5 proteins in response to PRL was investigated to establish the signaling pathway of PRL in the human endometrium. Endometrial tissue was collected during the secretory phase of the menstrual cycle and incubated in the presence of 100 ng/mL human PRL for 0, 5, 10, and 20 min. JAK2 phosphorylation was induced by PRL at 5 min, whereas STAT1 and STAT5 phosphorylation was apparent 20 min after stimulation with PRL. Immunohistochemistry localized the JAK/STAT proteins in the glandular epithelial cells and a subset of stromal cells, as was observed for the PRL receptor. Secretory phase stromal and glandular cells cultured separately and in the presence or absence of 100 ng/mL PRL confirmed the PRL-induced phosphorylation of JAK2/STAT proteins, at least in the glandular compartment. These studies demonstrate an up-regulation of expression of functional PRL receptors during the secretory phase of the menstrual cycle. Further, decidual PRL through a paracrine mechanism may influence glandular epithelial function/secretions and direct gene transcription through the JAK/STAT pathway. The target genes activated by PRL in the glandular epithelium of the nonpregnant human endometrium remain to be elucidated.
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PMID:Expression of functional prolactin receptors in nonpregnant human endometrium: janus kinase-2, signal transducer and activator of transcription-1 (STAT1), and STAT5 proteins are phosphorylated after stimulation with prolactin. 966 41

This study investigated the expression and signaling pathway of PRL and its receptor in the non-pregnant uterus of the common marmoset monkey. Immunohistochemistry localized PRL expression to the stromal compartment of the endometrium. Expression was minimal during the proliferative phase and was up-regulated during the mid to late secretory phase of the ovulatory cycle. In situ hybridization and immunohistochemistry localized expression of the PRL receptor to the glandular epithelium of the endometrium. Similar to that of PRL, PRL receptor expression was minimal during the proliferative phase and was dramatically up-regulated during the secretory phase. The temporal pattern of PRL receptor gene expression in the marmoset uterus across the cycle was further confirmed by ribonuclease protection assay. The roles of Janus kinase-2 (JAK2) and signal transducer and activator of transcription-1 (STAT1) in the intracellular signaling pathway of PRL were also assessed in the mid to late secretory phase. JAK2/STAT1 proteins were localized in the glandular epithelial compartment, and both proteins were temporally phosphorylated in response to PRL. Finally, the pattern of expression of the interferon regulatory factor-1 (IRF-1) gene and the effect of PRL on transcription of IRF-1 were investigated during the mid to late secretory phase. IRF-1 expression in the marmoset uterus was encoded by a protein of 48 kDa and was localized to the glandular epithelial compartment, as was observed for the PRL receptor and JAK2/STAT1 proteins. Moreover, incubation of mid to late secretory uterine tissue with PRL for 1 and 3 h resulted in 0.4 +/- 0.2- and 2.4 +/-0.5-fold (P < 0.05) inductions of the IRF-1 gene, respectively. These studies confirm the expression of both PRL and its receptor in the uterus of the marmoset monkey. Expression of both genes is up-regulated during the mid to late secretory phase of the ovulatory cycle. PRL function in the marmoset uterus is linked to the JAK/STAT signaling pathway, leading to the regulation of expression of PRL-responsive genes such as IRF-1. The site of expression of PRL, PRL receptors, and IRF-1 in the marmoset uterus suggest that PRL may influence glandular epithelial function and direct gene transcription in these cells in a paracrine fashion.
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PMID:Localization and signaling of the prolactin receptor in the uterus of the common marmoset monkey. 1077 Feb 19