Side-chain cleavage of cholesterol to C6 and C8compounds by adrenal and testis tissue preparations

Burstein, Shlomo; Zamoscianyk, Helen; Co, Nana; Adelson, Miriam; Prasad, Durga Shiv; Greenberg, Arthur; Gut, Marcel

doi:10.1016/0005-2760(71)90271-2

Cited by 30 publications

(9 citation statements)

References 11 publications

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“…A possible explanation for these findings is an alternate C27 -* C19 pathway, bypassing C21 intermediates (Jungmann 1968). Caution is indicated in this interpretation, since such a direct route of androgen biosynthesis has not been confirmed by other investigators (Hochberg et al 1971;Burstein et al 1971). …”

Section: Resultsmentioning

confidence: 79%

Metabolism of [4-14c]cholesterol by Human Adrenal Glands in Vitro and Its Inhibition by Metyrapone

Carballeira

Cheng

Fishman

1974

Acta Endocrinologica

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The in vitro conversion of [4-14C] cholesterol1) to steroid hormones was studied in 1 normal, 1 adenomatous and 2 hyperplastic, surgically resected, human adrenals. The degree of overall conversion per gram of tissue was similar (4.4\p=n-\5.6 %) in NADPH-supplemented homogenates from normal or moderately hyperactive adrenals; a 2-fold increase was found in a markedly hyperfunctioning gland. Only labelled cortisol, * Address reprint requests to A. is the abbreviation for adrenocorticotrophic hormone.

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Section: Resultsmentioning

confidence: 79%

Metabolism of [4-14c]cholesterol by Human Adrenal Glands in Vitro and Its Inhibition by Metyrapone

Carballeira

Cheng

Fishman

1974

Acta Endocrinologica

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“…If a pathway for the formation of dehydroepiandrosterone using as the proximal precursor either the 17-hydroperoxide or the 17,20-cyclic peroxide derivative of cholesterol exists, the side-chain cleavage product that would result from this conversion possibly contains eight carbon atoms. An intensive search for a C8 fragment accompanying the biosynthesis of a C19 steroid from cholesterol was made about a quarter of century ago (22)(23)(24), but none was found. If the path cholesterol -* cholesterol peroxide --dehydroepiandrosterone does exist in the brain or even in the steroid-producing endocrine glands, then it would undoubtedly be associated with its own regulatory system (trophic factors, etc.)…”

Section: Discussionmentioning

confidence: 99%

Precursors of the neurosteroids.

Prasad

Vegesna

Welch

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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In addition to the neurosteroids pregnenolone and dehydroepiandrosterone, organic solvent extracts of rat brains contain related compounds that react with various reagents to yield additional amounts of these ketosterolds. Among the chemicals producing these increments are triethylamine, HCI, FeCl3, and Pb(OAc) In a recent paper (1), estimates of the concentrations of five steroids and their conjugates in mammalian brains were recorded. Also described were the techniques used for the separation, identification, and quantification of these socalled neurosteroids. An unusual feature of the reported findings was the relatively high concentrations of steroidal conjugates, which were designated "sulfolipids." Following from our previous experience with analogous conjugates of cholesterol (2), we found that there appear to exist in mammalian brain nonpolar conjugates of neurosteroids, particularly pregnenolone (3f3hydroxy-5-pregnen-20-one) and dehydroepiandrosterone (3f-hydroxy-5-androsten-17-one).These, when treated with an organic base such as triethylamine or pyridine, were converted to a steroid sulfate that could be identified and quantified (after acid hydrolysis) as the free steroid. Some of these conjugates appeared to be present in relatively high concentrations in brain, suggesting that these conjugates play a physiological role in the nervous system.The experiments described in this paper bear on these substances. More The second part was separated into its ketonic and nonketonic (part B) components by treatment with polystyrenebenzyloxime resin to remove carbonyl compounds (8), including the endogenous ketosteroids and their derivatives. Sample B was dissolved in 20 ml of benzene containing 2 ml of acetic acid and a bolus of 200,000 dpm of tritiated pregnenolone. The oxime resin (100 mg) was added, and the suspension was stirred for 2 hr at room temperature. A check of the tritium content of the supernatant revealed that >90% of the tritiated steroid had bound to the resin. The reaction was allowed to proceed to Abbreviation: P450scc, side chain-cleaving P450.

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“…The extracts did not convert radiolabelled cholesterol to pregnenolone. whereas extracts from normal testicular tissue do (Burstein et al. 1971).…”

Section: H!~othalutnic-pituitar!~-goiiudul Iisismentioning

confidence: 99%

Congenital Adrenal Hyperplasia Due to Deficient Cholesterol Side‐chain Cleavage Activity (20, 22‐desmolase) in a Patient Treated for 18 Years

Hauffa¹,

Miller²,

Grumbach³

et al. 1985

Clinical Endocrinology

135

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Two siblings, a 9-week-old female and an 18-year-old male pseudohermaphrodite are described with deficient cholesterol side-chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycorticosterone and corticosterone were unmeasurable. Urinary 17-hydroxycorticosteroids (17-OHCS), tetrahydrocortisol, 17-ketosteroids (17-KS), pregnanetriol, pregnanediol, and delta 5-3 beta-ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radiolabelled cholesterol to pregnenolone. The gluccocorticoid and mineralocorticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocorticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long-term steroid replacement therapy, and comparison with previously reported findings are discussed.

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Side-chain cleavage of cholesterol to C6 and C8compounds by adrenal and testis tissue preparations

Cited by 30 publications

References 11 publications

Metabolism of [4-14c]cholesterol by Human Adrenal Glands in Vitro and Its Inhibition by Metyrapone

Metabolism of [4-14c]cholesterol by Human Adrenal Glands in Vitro and Its Inhibition by Metyrapone

Precursors of the neurosteroids.

Congenital Adrenal Hyperplasia Due to Deficient Cholesterol Side‐chain Cleavage Activity (20, 22‐desmolase) in a Patient Treated for 18 Years

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