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Decreased Sensitivity of Distal Nephron and Collecting Duct to Parathyroid Hormone in Pseudohypoparathyroidism Type I

MASAKO GOTO^*, KAZUTOSHI MIZUNASHI, NORIKO KIMURA and YOHTARO FURUKAWA

^* Miyagi Social Insurance Hospital, Sendai, Japan
The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
The Department of Pathology, Tohoku Rosai Hospital, Sendai, Japan.
Sendai Open Hospital, Sendai, Japan.

Correspondence to Dr. Kazutoshi Miaunashi, Second Department of Medicine, Tohoku University School of Medicine, Seiryocho 1-1, Aoba-ku, Sendai, 980-8574, Japan. Phone:; Fax: 81-22-2232077; E-mail: masakg2i{at}mail.cc.tohoku.ac.jp

Abstract

Abstract. Parathyroid hormone (PTH) transiently increases urinary excretion of the lysosomal enzyme, N-acetyl-ß-D-glucosaminidase, which is distributed mainly in proximal tubules. The response is reduced in pseudohypoparathyroidism (PHP) type I, which is characterized by target-organ resistance to PTH. Evidenced by normal calcium resorption, distal tubule sensitivity to PTH has been believed to be normal in this disorder. This hypothesis was tested through a search for another marker of distal nephron sensitivity to PTH. In the human kidney, cathepsin D was expressed predominantly in distal segments of the nephron, cortical and medullary thick ascending limbs of Henle's loop, distal convoluted tubules, and connecting tubules and in cortical collecting ducts and medullary collecting ducts. PTH infusion transiently increased cathepsin D excretion in normal subjects. The cathepsin D response to PTH was reduced in the patients with PHP type I. The decrease in cathepsin D response in PHP type I indicates a resistance to PTH in the distal nephron (cortical thick ascending limbs of Henle's loop, distal convoluted tubules, and connecting tubules) and cortical collecting ducts. These observations suggest that the preservation of renal tubular sensitivity to PTH in this disorder may be confined to PTH-dependent calcium resorption in distal tubules.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673