Proenkephalin A and the gamma-aminobutyric acid A receptor pi subunit: expression, localization, and dynamic changes in human secretory endometrium.

OBJECTIVE To compare mRNA and protein levels of proenkephalin A (PEA) and gamma-aminobutyric acid A receptor pi subunit (piGABA-R) in human secretory endometrium before and during receptivity and to determine the cell phenotypes where they are expressed. DESIGN Prospective and observational, comparing prereceptive vs. receptive stages of secretory endometrium within the same nonconceptional menstrual cycle. SETTING University and non-governmental organization (NGO)-based academic and clinical-research facilities. PATIENT(S) Seven healthy, multiparous, surgically sterilized women with spontaneous regular menstrual cycles. INTERVENTION(S) Endometrial biopsies were obtained on LH+3 and LH+7 within the same cycle. MAIN OUTCOME MEASURE(S) Levels of PEA and piGABA-R mRNA were determined by real-time PCR, and protein presence, by immunofluorescence. RESULT(S) The mRNA level of PEA fell, whereas that of piGABA-R increased, during endometrial receptivity. Positive immunostaining of PEA was found in the luminal and glandular epithelium, whereas that of piGABA-R was in luminal epithelium and stromal cells. CONCLUSION(S) The discrete cell-phenotype localization and timing of the changes in the level of PEA and of piGABA-R mRNA and protein suggest an important role for these molecules in switching the human endometrium from a refractory to a receptive state.