title: Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment.
abstract: Hypokalemic tubular disorders may lead to growth retardation which is resistant to growth hormone (GH) treatment. The mechanism of these alterations is unknown. Weaning female rats were grouped (n = 10) in control, potassium-depleted (KD), KD treated with intraperitoneal GH at 3.3 mg x kg(-1) x day(-1) during the last week (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth retarded compared with CPF rats, the osseous front advance (+/-SD) being 67.07 +/- 10.44 and 81.56 +/- 12.70 microm/day, respectively. GH treatment did not accelerate growth rate. The tibial growth plate of KD rats had marked morphological alterations: lower heights of growth cartilage (228.26 +/- 23.58 microm), hypertrophic zone (123.68 +/- 13.49 microm), and terminal chondrocytes (20.8 +/- 2.39 microm) than normokalemic CPF (264.21 +/- 21.77, 153.18 +/- 15.80, and 24.21 +/- 5.86 microm). GH administration normalized these changes except for the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes in their distribution as analyzed by immunohistochemistry and in situ hybridization. GH did not further modify IGF-I mRNA expression. KD rats had normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses the structural and molecular alterations induced by potassium depletion on the growth plate and shows that the lack of response to GH administration is associated with persistence of the disturbed process of chondrocyte hypertrophy and depressed mRNA expression of local IGF-I in the growth plate.
authors: Hospital Universitario Central de Asturias, Asturias, Spain.
authors: Helena
authors: H
authors: Gil-Peña
authors: Enrique
authors: E
authors: Garcia-Lopez
authors: Oscar
authors: O
authors: Alvarez-Garcia
authors: Vanessa
authors: V
authors: Loredo
authors: Eduardo
authors: E
authors: Carbajo-Perez
authors: Flor A
authors: FA
authors: Ordoñez
authors: Julian
authors: J
authors: Rodriguez-Suarez
authors: Fernando
authors: F
authors: Santos
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D049628:Body Size; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006132:Growth Plate / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006947:Hyperkalemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014886:Weaning; D015430:Weight Gain
chemical_list: D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1