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Pregnenolone

About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.


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Journal ArticleDOI
TL;DR: Results suggest the involvement of a haem-containing protein, ‘P-450’ as the oxygen-binding site in the cholesterol side-chain cleavage system of bovine adrenal cortex.
Abstract: 1 The cholesterol side-chain cleavage system of bovine adrenal cortex has been studied using extracts of sonicated mitochondria as source of enzymic activity. 2 The system has been found to be inhibited by carbon monoxide, this inhibition being consistent with competition between carbon monoxide and oxygen for an enzymic site. 3 The inhibition by carbon monoxide is reversed by light, the most effective wavelength being 450 mμ. These results suggest the involvement of a haem-containing protein, ‘P-450’ as the oxygen-binding site in the cholesterol side-chain cleavage system. 4 Attempts have been made to isolate intermediates between cholesterol and pregnenolone. Neither 20α-hydroxycholesterol nor 20α,22-dihydroxycholesterol have been found.

203 citations

Journal ArticleDOI
TL;DR: The most likely cause of the age-related decline in adrenal androgen biosynthesis is an age- related decline in the number of functional reticularis cells, without a major change in the differentiated properties of the zonal cells as a function of age.
Abstract: Based on indirect evidence, it has often been assumed that the zona reticularis of the adult human adrenal cortex is the source of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), but direct tests of this concept have been few. Using the techniques of cell culture, Northern blotting, and RIA, we compared the properties of separated adult zonal cells to those of fetal zone cells, a cell type well known to secrete large amounts of DHEA(S) due to its low expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). In nine glands from donors of a wide age range, the zona fasciculata and zona reticularis were separated and dissociated, and the cells were placed in culture. After 5 days, serum was removed by a 24-h period in serum-free defined medium followed by a 24-h exposure to cAMP analogs, with the optional addition of insulin, also in serum-free medium. The separated fasciculata and reticularis cells showed large differences in the DHEA(S)/cortisol (F) production ratios from added pregnenolone precursor, consistent with the synthesis of only F and essentially no DHEA(S) by fasciculata cells and with the synthesis of mostly DHEA(S) with little or no F by both reticularis cells and fetal zone cells. The different patterns of steroidogenesis were accompanied by a much lower level of expression of type II 3 beta HSD in reticularis cells, similar to that in fetal zone cells. In contrast, other genes were similarly regulated in the two adult zones and in the fetal zone by both cAMP and insulin. The levels of messenger ribonucleic acids for 17 alpha-hydroxylase, cholesterol side-chain cleavage enzyme, 21-hydroxylase, and 11 beta-hydroxylase responded to cAMP and insulin in both reticularis cells and fetal zone cells in the same pattern as that previously established in fasciculata cells. The central role of the limited expression of 3 beta HSD in the DHEA(S)-synthesizing property of reticularis cells was established by inhibition of 3 beta HSD in fasciculata cells with trilostane, which caused them to increase their DHEA/F production ratio to a level exceeding even that in fetal zone cells. There did not appear to any age-related changes in gene expression that could account for the large age-related decline in DHEA(S) biosynthesis in humans in either reticularis or fasciculata cells. Thus, the most likely cause of the age-related decline in adrenal androgen biosynthesis is an age-related decline in the number of functional reticularis cells, without a major change in the differentiated properties of the zonal cells as a function of age.

203 citations

Journal ArticleDOI
TL;DR: In this article, the selective expression of a 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) isoform in rat brain was reported.

202 citations

Journal ArticleDOI
TL;DR: Porcine adrenal microsomes contain a 17 alpha-hydroxylase/C17,20-lyase which is a single protein molecule readily purified to an enzymatically active form and the enzyme closely resembles that found in testicular microsome.

199 citations

Journal ArticleDOI
TL;DR: This review summarizes data in animals and humans in favor of a role of neurosteroids in cognitive aging and proposes the use of new methods of quantification of Neurosteroids as a useful tool for understanding their respective role in improving learning and memory impairments associated with normal aging and/or with pathological aging, such as Alzheimer's disease.

198 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202344
202255
202124
202028
201950
201835