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R B Clayton

Publications and source records attributed to R B Clayton.

At least 19 recordsLinked to original sources

Sexual differentiation of hepatic metabolism of corticosterone and testosterone in the rat.

The metabolism of corticosterone and testosterone has been studied in vitro in separate aliquots of the same homogenates of livers from neonatally masculinized and non-masculinized adult castrate male rats. The recovered metabolites were separated by TLC and identified by the combined use of GLC and appropriate derivative formation. The major effect of neonatal masculinization upon the metabolism of both steroids was to increase the ratio of 3 beta : 3 alpha metabolites but this effect was much more prominent in the metabolism of corticosterone than of testosterone. Only 5 alpha metabolites of corticosterone were found, whereas a minor amount of 5 beta products appeared in the case of testosterone. Reduction at C-20 accounted for only about 5% of the metabolism of corticosterone with the exclusive formation of 20 beta-hydroxy derivatives in the non-masculinized liver, but of both 20 alpha and 20 beta products in the masculinized liver. Small amounts of acetylated androstane 3,17-diols and 3-hydroxy-17-ketones were formed, apparently by enzymic reactions that are influenced by neonatal masculinization.

Animals↗

Dissociation of adrenal corticosteroid production from ACTH in water-restricted female rats.

These experiments were undertaken to investigate the mechanism whereby a precipitous drop in plasma corticosterone concentration is brought about following drinking in rats on a restricted water schedule. No alteration in adrenocorticotrophic hormone (ACTH) output was found, nor was catabolism of corticosterone sufficient to account for the drop. It is concluded that corticosterone level is controlled under these conditions by a mechanism independent of ACTH concentration.

Adrenal Glands↗

Strain-dependent gonadal effects upon adrenal cholesterol ester concentration and composition in C57BL/10J and DBA/2J mice.

The effects of gonadectomy and sex hormone administration on the concentrations of the individual cholesterol esters in the adrenals of C57BL/10J and DBA/2J mice are described. The methyl esters of the fatty acids derived from the cholesterol ester fraction have been analyzed by gas-liquid chromatography. In both strains the females have a higher total adrenal cholesterol ester concentration than the males. However, different gonadal effects operate in the two strains. In the C57 strain the presence of the ovary or the administration of estradiol benzoate to the ovariectomized female increases the concentrations of all adrenal cholesterol esters. This effect does not occur in the DBA strain. In the DBA strain the presence of the testes or the administration of testosterone propionate to the castrate male lowers the concentration of all adrenal cholesterol esters. This effect does not occur in the C57 strain. The response to testosterone propionate in the castrate male of the DBA strain is significantly greater than that of ovariectomized female. This finding suggests that sexual differentiation influences the magnitude of the response. In both strains cholesteryl adrenate (C22:4) shows these gonadal effects to a greater degree than the other adrenal cholesterol esters. Thus, there are at least two types of gonadal control of adrenal cholesterol esters. One of these affects all the esters in general while the other affects adrenic acid metabolism specifically.

Adrenal Glands↗

Strain-dependent gonadal effects upon the response of adrenal cholesterol esters to ACTH in C57BL/10J and DBA/2J mice.

The response of adrenal cholesterol esters to ACTH administered in vivo was studied in males, females and male castrates of the C57BL)10J and DBA/21 strains of mice. The cholesterol ester fatty acids were transmethylated and analyzed by gas-liquid chromatography. There are sex and strain differences in the response of the adrenal cholesterol esters to ACTH. Neither the male nor the female C57 mouse shows a significant depletion of total cholesterol esters upon ACTH treatment. This result argues against the utilization of adrenal cholesterol esters for corticosteroid synthesis in this strain. In the female DBA mouse cholesterol ester depletion in response to ACTH is maximal. Neither the total cholesterol ester concentration nor the concentration of any individual ester is correlated with the pattern of response of the cholesterol esters to ACTH. Among the individual cholesterol esters, cholesteryl arachidonate (C20:4) is preferentially utilized after ACTH treatment in all groups except the C57 males. In contrast, cholesteryl adrenate (C22:4), which is generally the most abundant cholesterol ester, is conserved during ACTH stimulation in all groups except the DBA females. A cyclic interconversion between adrenate and arachidonate may be physiologically important in the control of adrenal function.

Adrenal Glands↗

Stimulation of erythroblast maturation in vitro by sphingolipids.

A lipid factor previously isolated from leukocytes and found to stimulate basophilic erythroblast formation in an in vitro system of incubated rabbit bone marrow cells has been analyzed by thin-layer chromatography, gas-liquid chromatography, and gas-liquid chromatography-mass spectrometry. The biologically active components are sphingosine ceramides of tetracosanoic and dehydrotetracosanoic acids. Tests of a series of related ceramides show a high degree of structural specificity for the C(24)-V-acyl compounds with significant but markedly lower activity of the C(22) analog. Commercially available sphingomyelin shows activity comparable to that of the tetracosanoic acid ceramide. Sphingosine and tetracosanic acid supplied in equimolar amounts have negligible activity. The results, in the context of other findings, suggest a possible supportive role of plasma ceramides and sphingomyelins in red cell maturation.

Animals↗

An interstrain difference in cholesterol synthesis in vitro in mice, dependent upon a difference in endogenous NADPH-generating capacity.

Earlier experiments have shown that significantly more endogenously generated NADPH is available for reduction of corticosterone in liver homogenates from C57BL/10 male mice than in those from the DBA/2 strain. To test the effect of this interstrain difference upon a representative NADPH-requiring biosynthetic pathway in vitro, the biosynthesis of cholesterol from mevalonic acid was studied in homogenates of livers from the two strains of mice, with and without addition of an NADPH-generating system. The incorporation of mevalonic acid into cholesterol in homogenates from the C57BL/10 strain is little affected by omission of the NADPH-generating system, but in the DBA/2 strain, addition of an NADPH-generating system is necessary to elevate the level of cholesterol synthesis to that of the C57BL/10 strain. Without this addition, the DBA/2 homogenate mainly produces lanosterol and other precursors of cholesterol which require NADPH for their further metabolism.

Animals↗

Genetic variation of cholesterol ester content in mouse adrenals.

Total cholesterol concentrations in muscle, liver, and plasma do not differ significantly between adult male C57BL/10J and DBA/2J mice. In the adrenal glands of these two strains, of their hybrids, and of AC mice, concentrations of free cholesterol vary by 5 percent. Adrenals from C57 mice, however, contain six times as much esterified cholesterol as adrenals from AC or DBA mice. The intermediate concentrations of cholesterol esters in F(1) hybrids suggest that the difference in this measure is inherited additively. The finding of variation in adrenal cholesterol within a species is useful for the further study of the role of cholesterol in steroidogenesis by means of genetic analysis.

Adrenal Glands↗