title: Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats.
abstract: We hypothesized that progesterone-induced decrease in uterine fluid pH involves V-ATPase. In this study, expression and functional activity of V-ATPase in uterus were investigated under progesterone influence. Ovariectomized adult female rats received subcutaneous injection of estradiol-17β (1 µg/kg/day) or progesterone (20 mg/kg/day) for 3 days or 3 days estradiol-17β followed by 3 days vehicle, progesterone, or estradiol-17β plus progesterone. Mifepristone, a progesterone receptor blocker, was concomitantly given to the rats which received progesterone. A day after last injection, rate of uterine fluid secretion, its HCO3 (-) concentration, and pH were determined via in vivo uterine perfusion in rats under anesthesia. V-ATPase inhibitor, bafilomycin, was introduced into the perfusion buffer, and changes in these parameters were observed. Expression of V-ATPase A1 and B1/2 proteins and mRNAs in uterus were quantified by Western blotting and real-time PCR, respectively. Distribution of these proteins was observed by immunohistochemistry. Our findings showed that under progesterone influence, uterine fluid secretion rate, HCO3 (-) concentration, and pH were significantly reduced. Administration of bafilomycin did not cause significant changes in fluid secretion rate; however, HCO3 (-) concentration and pH were significantly elevated. In parallel with these changes, expression of V-ATPase A1 and B1/2 proteins and mRNAs were significantly increased with these proteins highly distributed in uterine luminal and glandular epithelia. In conclusion, increased expression and functional activity of V-ATPase were most likely responsible for the decreased in uterine fluid pH observed under progesterone influence.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Kamarulzaman
authors.initials: K
authors.lastname: Karim
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Nelli
authors.initials: N
authors.lastname: Giribabu
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Sekaran
authors.initials: S
authors.lastname: Muniandy
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. naguib.salleh@yahoo.com.my.
authors.forename: Naguib
authors.initials: N
authors.lastname: Salleh
mesh_terms: D000818:Animals; D015415:Biomarkers; D004717:Endometrium / Q000378:metabolism; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011374:Progesterone; D025262:Vacuolar Proton-Translocating ATPases
keywords: B1/2; Progesterone; Uterine fluid pH; V-ATPase A1