title: Decreased sensitivity of distal nephron and collecting duct to parathyroid hormone in pseudohypoparathyroidism type I.
abstract: Parathyroid hormone (PTH) transiently increases urinary excretion of the lysosomal enzyme, N-acetyl-beta-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.
authors.affiliation: Miyagi Social Insurance Hospital, Sendai, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Goto
authors.affiliation: The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Mizunashi
authors.affiliation: The Department of Pathology, Tohoku Rosai Hospital, Sendai, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kimura
authors.affiliation: Sendai Open Hospital, Sendai, Japan.
authors.forename: Yohtaro
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D002402:Cathepsin D / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009399:Nephrons / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000503:physiopathology*; D012016:Reference Values; D014018:Tissue Distribution
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; D000118:Acetylglucosaminidase; D002402:Cathepsin D