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Abstract
The Na-K-2Cl cotransporter (NKCC2) regulates sodium transport along the thick ascending
limb of Henle's loop and is important in control of sodium balance, renal concentrating
ability and renin release. To determine if there are sex differences in NKCC2 abundance
and/or distribution, and to evaluate the contribution of ovarian hormones to any such
differences, we performed semiquantitative immunoblotting and immunoperoxidase immunohistochemistry
for NKCC2 in the kidney of Sprague Dawley male, female and ovariectomized (OVX) rats
with and without 17-beta estradiol or progesterone supplementation. Intact females
demonstrated greater NKCC2 protein in homogenates of whole kidney (334+/-29%), cortex
(219+/-20%) and outer medulla (133+/-9%) compared to males. Ovarian hormone supplementation
to OVX rats regulated NKCC2 in the outer medulla only, with NKCC2 protein abundance
decreasing slightly in response to progesterone but increasing in response to 17-beta
estradiol. Immunohistochemistry demonstrated prominent NKCC2 labeling in the apical
membrane of thick ascending limb cells. Kidney section NKCC2 labeling confirmed regionalized
regulation of NKCC2 by ovarian hormones. Localized regulation of NKCC2 by ovarian
hormones may have importance in controlling sodium and water balance over the lifetime
of women as the milieu of sex hormones varies.
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