Proenkephalin A and the γ-aminobutyric acid A receptor π subunit: expression, localization, and dynamic changes in human secretory endometrium

Objective: To compare mRNA and protein levels of proenkephalin A (PEA) and γ-aminobutyric acid A receptor π subunit (πGABA-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 πGABA-R mRNA were determined by real-time PCR, and protein presence, by immunofluorescence. Result(s): The mRNA level of PEA fell, whereas that of πGABA-R increased, during endometrial receptivity. Positive immunostaining of PEA was found in the luminal and glandular epithelium, whereas that of πGABA-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 πGABA-R mRNA and protein suggest an important role for these molecules in switching the human endometrium from a refractory to a receptive state.