Na+,K+-ATPase activity and subunit protein expression: ontogeny and effects of exogenous and endogenous steroids on the cerebral cortex and renal cortex of sheep.
We examined the effects of development, exogenous, and endogenous glucocorticoids on Na(+),K(+)-ATPase activity and subunit protein expression in ovine cerebral cortices and renal cortices. Ewes at 60%, 80%, and 90% gestation, newborns, and adults received 4 dexamethasone or placebo injections. Cerebral cortex Na(+),K(+)-ATPase activity was higher (P < .05) in placebo-treated newborns than fetuses of placebo-treated ewes and adults, α(1)-expression was higher at 90% gestation than the other ages; α(2)-expression was higher in newborns than fetuses; α(3)-expression was higher in newborns than 60% gestation; β(1)-expression was higher in newborns than the other ages, and β(2)-expression higher at 60% than 80% and 90% gestation, and in adults. Renal cortex Na(+),K(+)-ATPase activity was higher in placebo-treated adults and newborns than fetuses. Cerebral cortex Na(+),K(+)-ATPase activity was higher in dexamethasone- than placebo-treated adults, and α(1)-expression higher in fetuses of dexamethasone- than placebo-treated ewes at 60% and 80% gestation. Renal cortex Na(+),K(+)-ATPase activity and α(1)-expression were higher in fetuses of dexamethasone- than placebo-treated ewes at each gestational age, and β(1)-expression was higher in fetuses of dexamethasone- than placebo-treated ewes at 90% gestation and in dexamethasone- than placebo-treated adults. Cerebral cortex Na(+),K(+)-ATPase activity, α(1)-expression, β(1)-expression, and renal cortex α(1)-expression correlated directly with increases in fetal cortisol. In conclusion, Na(+),K(+)-ATPase activity and subunit expression exhibit specific developmental patterns in brain and kidney; exogenous glucocorticoids regulate activity and subunit expression in brain and kidney at some ages; endogenous increases in fetal cortisol regulate cerebral Na(+),K(+)-ATPase, but exogenous glucocorticoids have a greater effect on renal than cerebral Na(+),K(+)-ATPase.
Department of Pediatrics, Women and Infants Hospital of Rhode Island, The Warren Alpert Medical School of Brown University, Providence, RI 02905,USA.
Chang-Ryul
CR
Kim
Grazyna B
GB
Sadowska
Stephanie A
SA
Newton
Maricruz
M
Merino
Katherine H
KH
Petersson
James F
JF
Padbury
Barbara S
BS
Stonestreet
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood*; D007672:Kidney Cortex / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D021122:Protein Subunits; D012756:Sheep; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D005938:Glucocorticoids; D021122:Protein Subunits; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase; D006854:Hydrocortisone