Corticosterone metabolism and membrane transport.
The mammalian kidney metabolizes virtually all of the steroid hormones. Corticosterone receptors have been found in the cortical collecting tubule, and at least four metabolites of the hormone have been identified in rat renal tissue and urine. The biologic activity of these metabolites is not completely known. In this study, we examined the functional effects of three of the metabolites of corticosterone on membrane transport in toad and turtle bladders; we also analyzed the oxidoreductase pathways for corticosterone metabolism. In the toad bladder, maximal water flow (vasopressin- and cyclic AMP-stimulated) was unaffected by corticosterone, 11-dehydro-20-dihydrocorticosterone (metabolite I) and 11-dehydrocorticosterone (metabolite IV); maximal water flow was significantly inhibited by 20-dihydrocorticosterone (metabolite II). Sodium transport in the toad bladder was stimulated by corticosterone, 11-dehydrocorticosterone and 20-dihydrocorticosterone. Analysis of the oxidoreductase pathways in this tissue revealed that most of the corticosterone was oxidized to 11-dehydrocorticosterone, a biologically active compound; 11-dehydrocorticosterone was further metabolized to 11-dehydro-20-dihydrocorticosterone, a biologically inactive compound. Only 6% of the parent compound was converted to 20-dihydrocorticosterone. In the turtle bladder, none of the metabolites tested altered hydrogen ion secretion over the time period studied; no significant biotransformation of corticosterone occurred in this tissue. As the metabolites of corticosterone found in toad bladder are the same as those identified in mammalian tissues, our studies suggest that some of them may be important modulators of sodium and water transport in the distal nephron. Our data further suggest that these compounds are likely not involved in the regulation of urinary acidification.
Sabatini
S
S
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430.
Hartsell
A
A
Meyer
M
M
Kurtzman
N A
NA
Hierholzer
K
K
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001711:Biotransformation / Q000502:physiology; D002024:Bufo marinus / Q000378:metabolism*; D003345:Corticosterone / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D015394:Molecular Structure; D012964:Sodium / Q000493:pharmacokinetics; D013045:Species Specificity; D014426:Turtles / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*
C060094:20-dihydrocorticosterone; D012964:Sodium; C003552:11-dehydrocorticosterone; D003345:Corticosterone