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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: The metabolism of various radiolabeled steroids by cultured human epidermal keratinocytes was studied in an attempt to identify the steroid-metabolizing enzymes present in these cells.
Abstract: The metabolism of various radiolabeled steroids by cultured human epidermal keratinocytes was studied in an attempt to identify the steroid-metabolizing enzymes present in these cells. Sulfatase activity was demonstrated in keratinocytes with either E1S or DS as substrates. The products of sulfatase action were E1 and DHEA, respectively. The specific activity of the enzyme was approximately 5- to 14-fold greater with E1S as the substrate compared with DS, and the rates of hydrolysis were linear with incubation time up to 3 h. The metabolism of DHEA by the keratinocyte 17 beta-HSOR-catalyzed reaction resulted in the predominant formation of 5-androstene-3 beta,17 beta-diol. The rate of formation of 5-androstene-3 beta,17 beta-diol was linear with time of incubation up to 18 h, and the specific activity of 17 beta-HSOR, with DHEA as the substrate, was greater in keratinocytes maintained in culture for 4 weeks compared with keratinocytes kept in culture for 1 week. Androstenedione was a minor product of DHEA metabolism. The metabolism of DHT by epidermal keratinocytes resulted in the formation of 5 alpha-androstanedione, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, androsterone, and isoandrosterone: the rates of formation of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol were linear with incubation time up to 24 h, and the specific activities of 3 alpha-HSOR and 3 beta-HSOR did not appear to change with keratinocyte time in culture up to 3 weeks. The metabolism of DOC by epidermal keratinocytes resulted in 5 alpha-dihydrodeoxycorticosterone production: the rate of formation of this metabolite was linear with incubation time up to 4 h. The metabolism of E1 by epidermal keratinocytes yielded E2, and that of E2 resulted in the formation of E1. The rate of E1 formation from E2, was approximately 10-fold greater than the rate of formation of E2 from E1; these rates were linear with incubation time up to 4 h. Epidermal keratinocytes maintained in culture did not metabolize androstenedione to either E1 or E2, and pregnenolone was not metabolized by these cells. This study serves to ascertain that epidermal keratinocytes express steroid 5 alpha-reductase, 17 beta-HSOR, 3 beta-HSOR, 3 alpha-HSOR, 3 beta-hydroxysteroid oxidoreductase-delta 5----4-isomerase, and sulfatase activities.

41 citations

Journal ArticleDOI
Hajime Ueshiba1, Marl Segawa1, Tokishi Hayashi1, Yukitaka Miyachi1, Minoru Irie1 
TL;DR: Serum concentrations of androstenedione, dehydroepiandrosterone, estrone, estradiol, 17-hydroxyprogesterone, pregnenolone, and testosterone were significantly higher in patients with adrenal hyperplasia than in those with an adenoma.
Abstract: We developed a method for simultaneously measuring steroid hormones in very small volumes of serum, using a combination of high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). By this method, aldosterone, cortisol, 11-deoxycortisol, estrone, estradiol, androstenedione, dehydroepiandrosterone, deoxycorticosterone, 17-hydroxyprogesterone, testosterone, pregnenolone, and progesterone could be determined in a single 100-microL aliquot of serum from normal adults and patients with Cushing's syndrome. The steroid profile associated with Cushing's syndrome caused by adrenal adenoma was quite distinct from that associated with the syndrome caused by adrenal hyperplasia. Serum concentrations of androstenedione, dehydroepiandrosterone, estrone, estradiol, 17-hydroxyprogesterone, pregnenolone, and testosterone were significantly higher in patients with adrenal hyperplasia than in those with an adenoma. We compared the results of this HPLC/RIA method with those of 125I RIAs. The use of a HPLC/RIA system to obtain an accurate and sensitive profile of a range of serum steroids, as described here, obviates the need for large volumes of blood.

41 citations

Journal ArticleDOI
TL;DR: An important role for neurosteroids in myelin repair has been demonstrated in the rodent sciatic nerve, where progesterone and its direct precursor pregnenolone are synthesized by Schwann cells.
Abstract: Some steroids are synthesized within the central and peripheral nervous system, mostly by glial cells. These are known as neurosteroids. In the brain, neurosteroids have been shown to act directly on membrane receptors for neurotransmitters. For example, progesterone inhibits the neuronal nicotinic acetylcholine receptor, whereas its 3α,5α-reduced metabolite 3α,5α-tetrahydroprogesterone (allopregnanolone) activates the A γ-aminobutyric acid receptor complex. Besides these effects, neurosteroids also regulate important glial functions, such as the synthesis of myelin proteins. Thus, in cultures of glial cells prepared from neonatal rat brain, progesterone increases the number of oligodendrocytes expressing the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phophodiesterase (CNPase). An important role for neurosteroids in myelin repair has been demonstrated in the rodent sciatic nerve, where progesterone and its direct precursor pregnenolone are synthesized by Schwann cells. After cryolesion ...

41 citations

Journal ArticleDOI
TL;DR: Although the reduction of androstenedione to testosterone was markedly impaired, estrone reduction to estradiol was essentially normal, suggesting that the defective enzyme is specific for some rather than all 17-ketosteroids.
Abstract: Testes of the Stanley-Gumbreck pseudohermaphrotic (Ps) rat secrete only 12–25% as much testosterone as normal (Nl) rats. To explain the mechanism of this defect, minces of testes from Ps and Nl animals were incubated with 14C-steroids, and radioactive testosterone precursors wereisolated by reverse isotope dilution. Pregnenolone, 17-hydroxyprogesterone and androstenedione were converted to testosterone in Nl testes, but in testes from Ps rats androstenedione was the predominant steroid isolated, indicating defective 17β-hydroxysteroid dehydrogenase. This enzyme defect was not corrected by treatment of Ps rats with HCG or by addition of a TPNH generating system to the incubation flasks. Although the reduction of androstenedione to testosterone was markedly impaired, estrone reduction to estradiol was essentially normal, suggesting that the defective enzyme is specific for some rather than all 17-ketosteroids. The data suggest that the enzyme defect is inherited and is unrelated to other conditions associat...

41 citations

Journal ArticleDOI
TL;DR: ACTH has been found to regulate intramitochondrial aqueous volumes in a cycloheximide-inhibitable manner, and it is proposed that these volume changes reflect an altered relationship of outer and inner membranes which may promote movement of cholesterol.
Abstract: The mechanism and properties of the adrenal cortex enzyme system which catalyzes the side chain cleavage of cholesterol to form pregnenolone are summarized. Cytochrome P-450scc, an integral inner mitochondrial membrane protein, interacts with its electron donor adrenodoxin via an aqueous-exposed (matrix side) site, and with its substrate cholesterol via an active site in communication with the hydrophobic phospholipid milieu. In a purified, phospholipid vesicle-reconstituted system, membrane-dissolved cholesterol interacts rapidly with and can be readily metabolized by the membrane-associated cytochrome, and thus represents a readily accessible cholesterol pool. Evidence for a rapidly metabolizable mitochondrial substrate pool (presumably that in the inner mitochondrial membrane) and the regulation by ACTH of cholesterol movement from other site(s) (presumably the outer mitochondrial membrane) into the reactive pool is reviewed; additional evidence is provided which supports the idea that the outer mitoch...

41 citations


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