title: Testosterone enhances calcium reabsorption by the kidney.
abstract: The kidney is a target tissue for androgens, but the role of these hormones in the regulation of calcium (Ca2+) reabsorption remains unclear. The present study examines the effects of testosterone on Ca2+ transport by the luminal membranes of proximal and distal nephrons of the rabbit kidney. Tubule suspensions were pre-incubated in the presence or absence of the hormone, and 45C2+ uptake by the luminal membranes was measured using the rapid filtration technique. In the proximal tubules, testosterone did not influence Ca2+ uptake. In the distal tubules, a 5 min incubation with the hormone increased this uptake with a maximal response at 10(-10)M. Ca2+ transport by the distal membranes shows a dual kinetics. Testosterone enhanced the Vmax value of the low affinity component. In an attempt to identify the underlying mechanisms involved in this action, several messenger inhibitors were introduced in the tubule suspension. PD 98059 and U0 126 as well as AG 99 and genistein interfered with the hormone action suggesting the implication of a MEK kinase and a tyrosine kinase. To determine the type of the channels involved in this effect, Ca2+ uptake was measured in the presence of diltiazem, omega-conotoxin MVIIC and mibefradil, i.e. selective inhibitors of the L-type, P/Q type and T-type channels. An inhibition of Ca2+ transport was observed exclusively with mibefradil. These results indicate that testosterone enhances Ca2+ transport by opening a T-type Ca2+ channel in the distal luminal membrane, via MEK kinase and tyrosine kinase dependent mechanisms.
authors.affiliation: Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital, 5415 l'Assomption Blvd, Montreal, Que., H1T 2M4, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Couchourel
authors.forename: Marie
authors.initials: M
authors.lastname: Leclerc
authors.forename: Janos
authors.initials: J
authors.lastname: Filep
authors.forename: Michèle G
authors.initials: MG
authors.lastname: Brunette
mesh_terms: D000042:Absorption; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D020748:Mibefradil / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D000728:Androgens; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020865:Calcium Channels, P-Type; D020747:Calcium Channels, T-Type; D004791:Enzyme Inhibitors; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020748:Mibefradil; D013739:Testosterone; D011505:Protein-Tyrosine Kinases; D020930:MAP Kinase Kinase Kinases; D004110:Diltiazem; D002118:Calcium