Isolation and Metabolism of Male Sex-Dependent Urinary Protein From Rats

Geertzen, H. G. M.; Ouderaa, F. J. G. v. d.; Kassenaar, A. A. H.

doi:10.1530/acta.0.0720197

Cited by 26 publications

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“…There is evidence that this protein is synthesized in the liver, concentrated in the kidneys and excreted with the urine. Following nephrectomy the plasma levels rise, indicating the extrarenal source of this protein (Geertzen, van der Ouderaa & Kassenaar, 1973). In addition to a high physiological level of proteinuria, spontaneous kidney disease-characterized by progressive glomerulonephrosis with glomerulosclerosis-has repeatedly been described in Wistar rats (Kraus & Cain, 1974;Elema & Arends, 1975) and several other strains (Snell, 1967;Couser & Stilmant, 1975;Bolton, Benton, Maclay & Sturgill, 1976), the males being more severely affected than the females.…”

Section: Discussionmentioning

confidence: 99%

Proteinuria in rats in relation to age-dependent renal changes

et al. 1980

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Wiechert-A llee 9, 3000 Hannover 6I, and 3Zentralinstitut fiir Versuchstiere, Let/ow-Vorbeck-A llee 57, 3000Hannover 91, Federal Republic of Germany 95 Summary A variety of sex-dependent urinary proteins of low molecular weight, absent in females and in castrated males, can be identified in male rats by disc electrophoresis. In the urine of male rats of age 5·5 months, albumin comprises only 1-2% of the total protein. Albumin excretion increases greatly with age and associated kidney disease. Total protein excretion, however, stays the same or even decreases slightly as the rat ages, due to a loss of low molecular weight, sex-dependent, proteins. These are virtually absent in senescent rats (38 months of age), although total protein excretion rises tenfold in these animals due to high molecular weight plasma proteins passing into the urine; the glomerular filtration rate decreases to 70% of the value measured at 5·5 months of age.

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Section: Discussionmentioning

confidence: 99%

Proteinuria in rats in relation to age-dependent renal changes

et al. 1980

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“…It is catabolized slowly relative to most other proteins in the glomerular filtrate, with a half-life in plasma, kidney cytosol, or lysosomal preparations of5-8 hr (32,34,83). In vitro studies indicate that a20-g is more resistant than bovine ,3-lactoglobulin and lysozyme to lysosomal enzyme digestion (84).…”

Section: Factors Affecting Kidney Accumulation Of Low Molecular Weighmentioning

confidence: 99%

“…The plasma half-lives of many low molecular weight proteins are typically measured in minutes (30). a2u-Globulin, with a half-life measured in hours (34), is one of the exceptions.…”

Section: Introductionmentioning

confidence: 99%

Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

Hard

Rodgers

Baetcke

et al. 1993

Environ Health Perspect

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This review paper examines the relationship between chemicals inducing ewessive accumulation of a2u-globulin (ai21g) (CIGA) in hyline droplets inmale rat kidneys and the subsequent development of nephoit and rnal tubule nopaia in the male rt. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens fromclssical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity. CIGA or their metabolites bind specifically, but reversibly, tomale rat a2,-g The resulting complex appears to be more resistant to hydrolytic degradation in the proximaltubule than native, unbound a2,-g Singlecell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell prolifertin, foci oftubulehyerl a inthe aovoited pronal bules, and renal tubule tumor Although stnrcturally similar proteins have been detected in other species, including hu_ms, renal lesios characteristic Of a2,-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an ae,-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development ofrenal tubule tumors in male rats Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing a2.-g accumulation are unlikely to occur in humans. IntroductionFor most hazardous chemicals, adequate human data are not available, and risk analyses must rely on information from laboratory studies of rats or mice. The inference that the results ofanimal experiments can be applied to humans is a fundamental principle of all toxicologic research. This analysis deals with a specific case, however, where the male rat seems to respond in a manner different from other laboratory species. The possibility of a unique response in the rat among laboratory animals raises questions about the applicability of the rat data to other species, including humans. Our review evaluates the matter of human 'Medical Research Council relevance and describes the types of information needed for hazard assessment of such chemicals.A variety of organic chemicals have produced specific renal lesions in male rats in the form of a protein (hyaline) droplet nephropathy accompanied by accumulation of a2%-globulin (a2.-g) [reviewed in (1,2)]. Among the chemicals tested are paraffins (3,4), decalin (decahydronaphthalene) (5,6), petroleum-based and synthetic fuels (7), military aviation propellants (8), and 2,2,4-trimethylpentane (TMP) (9). As seen in Table 1, which lists a sampling ofchemicals that have been tested, many are of considerable regulatory and commercial interest. For example, isophorone is a chemical intermediate of major industrial importance. Aviation and automotive fuels fit i...

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“…Isolation of cn2u-globulin The purification procedure was adapted from methods published previously by Roy, Neuhaus & Harmison (1966) and Geertzen et al (1973). Samples of urine were collected from male rats housed in metabolic cages for 1 day and during the collection period, neither food nor water were provided.…”

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confidence: 99%

RELATIONSHIP BETWEEN THE PITUITARY GLAND AND GONADAL STEROIDS: INVOLVEMENT OF A HYPOPHYSIAL FACTOR IN REDUCED α2u-GLOBULIN AND INCREASED TRANSCORTIN CONCENTRATIONS IN RAT SERUM

Vandoren¹,

Baelen²,

Verhoeven³

et al. 1978

Journal of Endocrinology

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Evidence is presented that the level of alpha 2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats alpha 2u-globulin cannot be detected. Moreover, alpha 2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of alpha 2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of alpha 2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of alpha 2u-globulin.

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Isolation and Metabolism of Male Sex-Dependent Urinary Protein From Rats

Cited by 26 publications

References 0 publications

Proteinuria in rats in relation to age-dependent renal changes

Proteinuria in rats in relation to age-dependent renal changes

Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

RELATIONSHIP BETWEEN THE PITUITARY GLAND AND GONADAL STEROIDS: INVOLVEMENT OF A HYPOPHYSIAL FACTOR IN REDUCED α2u-GLOBULIN AND INCREASED TRANSCORTIN CONCENTRATIONS IN RAT SERUM

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