Effects of thyroid deficiency on the vasopressin receptors in the kidney of developing and adult rats. A comparative study of hormonal binding and adenylate cyclase activation.
The effects of propylthiouracil (PTU) treatment on renal vasopressin sensitive adenylate cyclase in young and adult rats were studied by measuring the binding of tritiated vasopressin and adenylate cyclase activation by vasopressin in kidney medulla plasma membranes. Thyroxine therapy completely corrected the effects of PTU treatment on the vasopressin-adenylate cyclase system. Thus, the abnormalities observed after a such treatment are directly related to thyroid deficiency and not to toxic effects of PTU. The inability of the kidney to normally concentrate urine in developing and adult animals with induced hypothyroidism was mainly related to the reduction of the number of binding sites without significant changes in the basal and guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, the apparent dissociation constant (Kbind) of labeled vasopressin from its specific receptor and the apparent activation constant (Kact) of vasopressin for adenylate cyclase. These results also show that thyroid deficiency has more effect on the ontogenesis of receptors than on their turnover, and demonstrate that a normal antidiuretic response occurs at very low receptor occupancy. Since, on the one hand, the hypothyroidism-induced abnormalities in renal medulla responsiveness to vasopressin were reversible and, on the other, only a permanent therapy consisting of two daily physiological doses of thyroxine from birth to the age of sacrifice fully restored them, the responsiveness of developing kidney to thyroid hormones appears to be fundamentally different from that of the CNS.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007037:Hypothyroidism / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism; D009994:Osmolar Concentration; D011441:Propylthiouracil; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin; D013974:Thyroxine / Q000627:therapeutic use; D014556:Urine; D014667:Vasopressins / Q000378:metabolism* / Q000494:pharmacology
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D006165:Guanylyl Imidodiphosphate; D011441:Propylthiouracil; D000262:Adenylyl Cyclases; D013974:Thyroxine