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Query: UMLS:C0338671 (Steroids)
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Steroids in the mono- and disulfate fractions from plasma of pregnant chimpanzees (Pan troglodytes), orangutans (Pongo pygmaeus), and a rhesus monkey (Macaca mulatta) were identified by gas chromatography/mass spectrometry and quantitated by gas-liquid chromatography on open tubular glass capillary columns. Whereas the average total concentrations were 4-5 times lower, 2.3-5.5 mumol X 1(-1) vs. 10.7-19.8 mumol X 1(-1), the pattern of steroid sulfates in the chimpanzees and orangutans were very similar to that previously found in pregnant women. Twenty one steroids were identified. The 3 beta-hydroxy-5-ene steroids were the same as in humans. Saturated pregnane derivatives were predominant and increased with time during pregnancy. Four isomers each of 3-hydroxypregnan-20-one and pregnane-3,20 alpha-diol were found, having 3 alpha, 5 alpha, 3 beta, 5 beta, 3 alpha, 5 beta, and 3 beta, 5 alpha stereochemistry, respectively. The relative proportion of disulfates was slightly lower in the great apes (15-28% of the total steroid sulfates) than in humans (23-33%). The monosulfate of 5 beta-pregnane-3 alpha, 20 alpha-diol constituted 12-14% of the total in chimpanzees and 3-4% in orangutans and humans. The monosulfate of 5 alpha-pregnane-3 beta, 20 alpha-diol constituted 5-7% in chimpanzees and 11-16% in orangutans and humans, whereas the disulfate was relatively less abundant in the great apes, 4-8%, than in humans, 10-18%. Although difficult to quantitate accurately, the chromatograms indicated that the proportion of 3 beta, 5 beta-isomers was higher in great apes than in women. The presence of 5 alpha-pregnane-3 beta, 16 alpha, 20 alpha-triol and 5 alpha-pregnane-3 alpha, 20 alpha, 21-triol indicated that hydroxylations of steroid sulfates in the great apes were similar to those in pregnant women. The steroid sulfate pattern in the rhesus monkey was completely different, 3 beta-hydroxy-5-ene steroids constituting over 95% of the total. Dehydroepiandrosterone sulfate was by far the predominant steroid, followed by the disulfates of 5-androstene-3 beta, 17 beta-diol and 5-pregnene-3 beta, 20 alpha-diol and the monosulfate of 5-androstene-3 beta, 16 alpha, 17 beta-triol. The results are discussed in relation to previous knowledge of progesterone metabolism in different animal species. So far, great apes are the only species showing the same pattern of steroid sulfates in plasma as humans.
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PMID:Identification and quantitation of steroids in sulfate fractions from plasma of pregnant chimpanzee, orangutan, and rhesus monkey. 669 Feb 81

The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001), (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%, p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%, p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol, +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha-THDOC (+309%, p<0.001). 3alpha,5beta-THDOC levels were increased by 307%, although this increase was not significant because this steroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.
Steroids
PMID:Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. 1917 Nov 60