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

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 elucidate d; however, the pattern of expression supports a role for PRL during i mplantation and placentation. This study investigated the site and pat tern of expression of PRL receptors in the nonpregnant human endometri um. In situ hybridization and immunohistochemistry localized expressio n of the receptor in the glandular epithelium and a subset of stromal cells of the endometrium. As judged by the intensity of staining, expr ession of the receptor was dramatically up-regulated during the secret ory phase. Expression of the PRL receptor gene in the endometrium from the secretory phase of the menstrual cycle was confirmed by ribonucle ase protection assay using 50 mu g total ribonucleic acid. Phosphoryla tion of Janus kinase-2 (JAK2), STAT1 (signal transducer and activator of transcription-1), and STAT5 proteins in response to PRL was investi gated to establish the signaling pathway of PRL in the human endometri um. 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 afte r stimulation with PRL. Immunohistochemistry localized the JAK/STAT pr oteins in the glandular epithelial cells and a subset of stromal cells , as was observed for the PRL receptor. Secretory phase stromal and gl andular cells cultured separately and in the presence or absence of 10 0 ng/mL PRL confirmed the PRL-induced phosphorylation of JAK2/STAT pro teins, at least in the glandular compartment. These studies demonstrat e an up-regulation of expression of functional PRL receptors during th e secretory phase of the menstrual cycle. Further, decidual PRL throug h a paracrine mechanism may influence glandular epithelial function/se cretions and direct gene transcription through the JAK/STAT pathway. T he target genes activated by PRL in the glandular epithelium of the no npregnant human endometrium remain to be elucidated.