Differential regulation of renal sodium-phosphate transporter by glucocorticoids during rat ontogeny.
The effects of chronic administration of methylprednisolone (MP) were studied on the ontogeny of the renal type II Na-P(i) transporter (NaPi-2). Immunoblot analysis showed that MP did not alter the expression of NaPi-2 protein levels in suckling and weanling rats; however, there was an approximately 50% decrease in adolescent and adult rats. There was no change in Na-dependent P(i) uptake in brush-border membrane vesicles in suckling rats, but there was an almost twofold decrease in adolescent rats induced by MP treatment. MP administration did not alter mRNA levels in suckling or adolescent rats. Dual injections with the glucocorticoid receptor blocker RU-486 (mifepristone) and MP did not reverse the downregulation of NaPi-2 immunoreactive protein levels in adolescent rats. To control for RU-486 antagonism efficiency, Na/H exchanger isoform 3 (NHE3) protein levels were also assayed after injection with RU-486 and MP. As expected, NHE3 protein levels increased after MP injection; however, the increase was blocked in adolescent rats by RU-486. We conclude that there is an age-dependent responsiveness to glucocorticoids and that the marked decrease in NaPi-2 immunoreactive protein levels and activity in adolescent rats is due to posttranscriptional mechanisms.
Guner
Y S
YS
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Kiela
P R
PR
Xu
H
H
Collins
J F
JF
Ghishan
F K
FK
D000199:Actins / Q000032:analysis / Q000276:immunology; D000367:Age Factors; D000818:Animals; D000918:Antibody Specificity; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics; D006727:Hormone Antagonists / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry* / Q000254:growth & development*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000493:pharmacokinetics; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
D000199:Actins; D002352:Carrier Proteins; D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D015735:Mifepristone; D012964:Sodium; D005947:Glucose; D008775:Methylprednisolone