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Search for other papers by E. BEDRAK in
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Search for other papers by V. SAMOILOFF in
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SUMMARY
A single intraperitoneal injection of 2 μg. d-aldosterone monoacetate/g. body weight produced a rapid, but temporary, uncoupling of oxidative phosphorylation in mouse liver mitochondria. This resulted in low P:O ratios in male and female animals of 1·21 and 1·52, respectively. The P:O ratio of females remained somewhat lower than the control levels but there was a progressive improvement in oxidative phosphorylation during the first 24 hr. after the injection leading to P: O ratios similar to those in the controls. Experiments in vitro showed that the uncoupling effects of aldosterone were related to its concentration in the reaction medium. Aldosterone added to fresh rat liver mitochondria, at concentrations of 10−10, 10−7 and 10−4m inhibited phosphorylation by 9·5, 77·1 and 95·1% and lowered P:O ratios to 2·46, 1·66 and 0·41, respectively. These changes in oxidative phosphorylation were not related to alteration in ATPase activity and were independent of mitochondrial electrolyte concentration.
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Search for other papers by Z. FINKELSTEIN in
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SUMMARY
Testosterone synthesis was studied in Acomys cahirinus by incubation of its testis with radioactive substrates. In comparison with other rodents, the Acomys testis was found to have a lower 17β-hydroxysteroid oxidoreductase activity, whereas the activity of 20α-hydroxysteroid oxidoreductase was high. The accumulation of 5-ene-3β-hydroxy metabolites suggested that biosynthesis proceeded preferentially by the 4-ene route. This was confirmed by the simultaneous incubation of [3H]5-ene-3β-hydroxysteroids and [14C]4-en-3-oxosteroids. The predominant route of biosynthesis would, therefore, appear to be: pregnenolone → progesterone → 17α-hydroxyprogesterone → androstenedione → testosterone.
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Search for other papers by U. A. SOD-MORIAH in
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SUMMARY
The metabolism of 3β-hydroxysteroids, in the presence of NADPH, by testicular homogenates of adult rats acclimatized to a hot environment (33–35 °C, 25–40% relative humidity), was compared with that of control and surgically produced cryptorchid testes. Prolonged exposure to a hot environment stimulated the transformation of 3β-hydroxysteroids to 3-oxo-4-ene metabolites, so that relatively large amounts of the latter accumulated. Pregnenolone was metabolized rapidly to progesterone, 17α-hydroxyprogesterone, androstenedione and testosterone. A similar trend was observed in the metabolism of 17α-hydroxypregnenolone. In-vitro synthesis of testosterone in the rat apparently takes place primarily by the 4-ene pathway. The 5-ene-17,20-lyase reaction appears to be rate-limiting. Heat acclimatization does not seem to affect this step. It does, however, seem to enhance the conversion of dehydroepiandrosterone via 5-androstene-3β,17β-diol to testosterone. Enzymic activity was much lower in cryptorchid than in heat-acclimatized testes, where it actually increased, except for 17β-hydroxysteroid oxidoreductase.
Continuous exposure of rats to a high ambient temperature for 4–6 months tended to decrease testosterone concentration in peripheral blood, and retarded growth rate and gonadal size. Histological examination showed atrophied areas in the testes where necrobiosis of the germinal epithelium had occurred. These necrotic foci, unlike those found in cryptorchid testes, were randomly scattered among intact seminiferous tubules in which active spermatogenesis was taking place.
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Search for other papers by G. M. GOLDBERG in
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SUMMARY
Prolonged aldosterone administration to mice was investigated in relation to liver function. Daily injections of 2 μg. d-aldosterone monoacetate/g. body weight for 60 days adversely affected oxidative phosphorylation of liver mitochondria. The value for the P:O ratio of controls, 3·21, dropped to 2·01, 2·86, 2·45 and 2·79 for mice treated with aldosterone for 20, 30, 50 and 60 days, respectively. The impaired oxidative phosphorylation was neither accompanied by an increase in adenosine triphosphatase activity of liver mitochondria nor by a change in plasma transaminases. Corresponding morphological changes were observed in liver parenchyma starting with hydropic degenerations in early lesions, and single cell necrosis accompanied by mitotic activity (regeneration) in advanced lesions. It seems therefore that hyperaldosteronism might be noxious to liver parenchyma and hepatic function.
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Search for other papers by U. A. SOD-MORIAH in
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Search for other papers by S. GOLDBERG in
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SUMMARY
The relative activities of enzymes participating in the biosynthesis of testosterone via the 4-ene pathway were determined in testicular homogenates of rats acclimatized to a hot environment (33–35 °C, 25–40% relative humidity). Acclimatized animals showed an increase in activity of 17α-hydroxylase, 17,20-lyase and 20α-hydroxysteroid oxidoreductase, whereas the activity of 17β-hydroxysteroid oxidoreductase was markedly decreased. Histological examination of the testes disclosed that neither the germinal epithelium nor the Leydig cells were adversely affected by the increased environmental temperature. The results are discussed in relation to the synthesis and release of the gonadotrophins.
A similar degree of acclimatization, as determined by the comparable decrease in oxygen uptake, was achieved by either of two methods: daily 4 h exposure to a high ambient temperature for 4 weeks or continuous maintenance at 35 °C. The former procedure, however, appeared to be the preferred method for acclimatization of male rats since it did not inhibit growth rate and was free of mortality.