This second revision of an R29 application seeks to advance our understanding of the molecular mechanisms by which the movement of water across the human cervical epithelial barrier. The applicant will use cultured human epithelial cell models developed in his laboratory to explore three hypotheses: 1) that estrogen increases transcervical permeability by means of an effect on cervical cell tight junctions, 2) that estrogen increases calcium mobilization in the cells, which in turn increases the permeability of the intercellular space, and 3) that the mechanism of Ca++ mobilization in the human cervical cell is a Ca++-dependent stimulation of cellular KCl transport, which results in a reduction in cell volume. It is proposed that the results of these studies will increase both our understanding of the basic biology of cervical fluid homeostasis, but also a better understanding of clinically relevant settings in which the cervical fluid status is abnormal.
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