Estrogen and androgen regulation of plasma membrane calcium pump activity in immortalized distal tubule kidney cells

Abstract

The ATP dependent plasma membrane calcium pump (PMCA) is a regulator of renal calcium reabsorption. The effect of estrogen and dihydrotestosterone to increase the activity of the PMCA in membrane vesicle preparations from a distal tubule cell line was investigated. 17β Estradiol (10 −10 M) increased PMCA activity (1.5±0.2-fold increase compared to control) with 24 h, but not 1 or 5 h, of exposure, an effect that was blocked by the addition of the estrogen antagonist ICI 164384. α Estradiol did not increase PMCA activity. Dihydrotestosterone (10 −11 M ) resulted in a dose dependent increase in PMCA activity (1.5±0.1-fold increase compared to control) with 24 h, but not 1 or 5 h, of exposure, an effect that was blocked by the androgen receptor agonist flutamide. Testosterone (10 −5 M) also increased PMCA activity (1.9±0.3-fold increase compared to control). Neither estrogen nor dihydrotestosterone increased PMCA protein expression in MDBK cells, indicating that these hormones increase PMCA activity by regulating PMCA activity rather than PMCA expression. These results demonstrate receptor dependent stimulatory effects of both estrogen and dihydrotestosterone to increase PMCA activity. and have significance for our understanding of estrogen and androgen deficient states on calcium transport.