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Effects of estrogen on proton secretion via the apical membrane in vaginal-ectocervical epithelial cells of postmenopausal women

Gorodeski, George I MD, PhD

doi: 10.1097/01.gme.0000184423.88814.e6

Objective: To understand estrogen regulation of proton (H+) secretion by human vaginal-ectocervical epithelial cells and the mechanisms involved.

Design: Primary-tertiary cultures of human normal vaginal-ectocervical epithelial cells were generated from surgical specimens of premenopausal women (aged 37-46 years) and of postmenopausal women (aged 53-65 years). Cells were grown on filters, and measurements were made of changes in extracellular pH (pHo) in the contraluminal (CL) and luminal (L) solutions 30 minutes after shifting cells to basic salt solution.

Results: Upon shifting cells to basic salt solution, CL-pHo decreased from 7.4 to 7.25, and was not affected by removal of intracellular estrogens or treatment with estradiol. L-pHo decreased from 7.4 to 7.05 in cells of premenopausal women, and from 7.4 to 7.20 in cells of postmenopausal women. Removal of intracellular estrogens attenuated the decrease in L-pHo in cells of premenopausal women (only to 7.20). In cells of premenopausal women stripped of estrogens, treatment with 10 nM 17β-estradiol restored the decrease in L-pHo. In estrogen-stripped cells of postmenopausal women, treatment with estradiol augmented luminal acidification but to a lesser degree than in cells of premenopausal women (L-pHo of 7.15 vs 7.05). In cells of pre- and postmenopausal women, the addition in the L solution of bafilomycin-A1, a specific inhibitor of the vacuolar-H+-ATPase (V-H+-ATPase), blocked the decrease in L-pHo.

Conclusions: Human vaginal-ectocervical epithelial cells acidify constitutively their luminal solution, and the effect is mediated by active H+ secretion by V-H+-ATPase expressed predominantly in the apical cell membrane. Estrogen deprivation attenuates, and treatment with 17β-estradiol augments, active H+ secretion. Finally, cells of postmenopausal women actively secrete H+ via apically located V-H+-ATPase, but the effect is lesser, and estrogen failed to augment active H+ secretion, as in cells of premenopausal women. These data suggest that in addition to hypoestrogenism, other factors of the aging process affect the capacity of vaginal-ectocervical cells to secrete acid.

Vaginal-ectocervical epithelial cells acidify constitutively their luminal solution by active, estrogen-dependent, H+ secretion via apically expressed V-H+ = ATPase. Estrogen deficiency inhibits, and treatment with estrogen enhances the effect, but estrogen effect in cells of postmenopausal women is smaller than in cells of premenopausal women, suggesting that aging affects the capacity of acid secretion.

From the Departments of Reproductive Biology, Oncology, and Physiology and Biophysics, CASE (Case Western Reserve) University, Cleveland, OH.

Received November 16, 2004; revised and accepted March 17, 2005.

The study was supported by National Institute of Health Grants HD29924 and AG15955 (GIG), and by the Tissue Procurement Core Facility of the Comprehensive Cancer Center of Case Western Reserve University and University Hospitals of Cleveland (P30 CA43703). Discarded tissues were collected according to IRB protocol 03-90-TG.

Address correspondence to: George I. Gorodeski, MD, PhD, University MacDonald Women's Hospital, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail:

©2005The North American Menopause Society