Enzymic synthesis of steroid sulphates XIV. Properties of human adrenal steroid alcohol sulphotransferase

Adams, J.B.; McDonald, D.

doi:10.1016/0005-2760(81)90124-7

Cited by 21 publications

(9 citation statements)

References 10 publications

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“…Celecoxib inhibited the sulfonation of DHEA in a concentration-dependent manner with an IC 50 of 82 μM (Figure 5A). Sulfonation of AD with SULT2A1 produced only one metabolite, which was assigned as AD–3-sulfate based on previous reports because AD–3-sulfate is unavailable commercially [46, 47]. Celecoxib inhibited the production of AD–3-sulfate with an IC 50 of 88 μM celecoxib (Figure 5A).…”

Section: Resultsmentioning

confidence: 84%

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Ambadapadi

Wang

Palii

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17βestradiol (17β-E2) from the 3- to the 17-position. The effects of celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1-catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3β, 17β-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration-dependent manner. Low μM concentrations of celecoxib strikingly enhanced the formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17β-dihydroequilenin (17β-Eqn), 17β-dihydroequilin (17β-Eq), and 9-dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2, 9D-E2 and 17β-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of 17β-Eq was stimulated at celecoxib concentrations below 40 μM. Ligand docking studies in silico suggest that celecoxib binds in the substrate-binding site of SULT2A1 in a manner that prohibits the usual binding of substrates but facilitates, for appropriately shaped substrates, a binding mode that favors 17-sulfonation.

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Section: Resultsmentioning

confidence: 84%

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Ambadapadi

Wang

Palii

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…This rather paradoxical behavior is due to the ability of the steroid to approach the sulfurylation site via (i) ring A with the /?-side upwards, and in this mode 3j8-hydroxyl groups are sulfurylated at a greater rate than 3a-hydroxyls, or (ii) ring D with the /3-side downwards, and in this mode 17a-hydroxyl groups are oriented in an analogous fashion to 3/3-hydroxyls and are sulfurylated at rapid rates. Only monosulfates are formed from steroids possessing more than 1 hydroxyl group (12). The enzyme exhibits unusual kinetics with DHEA as the variable substrate.…”

Section: Discussionmentioning

confidence: 99%

“…At DHEA concentrations in the 0.5-0.9 juM range, negative cooperativity is found which could desensitize the enzyme to minor changes in steroid levels. However, at a DHEA concentration of approximately 1 JUM, positive cooperativity is exhibited which would enable the enzyme to respond to sudden increases in the flux of DHEA as a result of ACTH stimulation (12).…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone Sulfotransferase Localization in Human Adrenal Glands: A Light and Electron Microscopic Study*

Kennerson

McDonald

Adams

1983

The Journal of Clinical Endocrinology & Metabolism

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Dehydroepiandrosterone sulfate is the major secretory product of the human adrenal cortex. The enzyme responsible for the sulfurylation, which has been isolated previously, possesses kinetic properties suggesting that it plays an important regulatory role in dehydroepiandrosterone sulfate secretion. In order to study the localization of the enzyme in the respective zones and cells of the cortex, an antibody to the pure enzyme was raised and the immunoglobulin G fraction employed in the peroxidase-antiperoxidase method. Staining was confined to the zona reticularis but was unevenly distributed throughout the cells. Electron microscopic examination of sections prepared from fresh adrenal tissue fixed in glutaraldehyde, revealed that the enzyme was predominantly clustered around lipid droplets. It is suggested that this may reflect an association of organelles, cholesterol being transported from lipid droplets to surrounding mitochondria, and pregnenolone then being converted to dehydroepiandrosterone in the adjacent endoplasmic reticulum and thence immediately sulfurylated.

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“…Sulfotransferases catalyze the transfer of a sulfuryl group, SO,, from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to compounds bearing amino or hydroxyl groups, thus forming the corresponding sulfamates or sulfate esters, respectively. Cytosolic sulfotransferases have been described with specificities for phenols (EC 2.8.2.1; Baranczyk-Kuzma and Szymczyk, 1986; , tyrosine-ester (Rens-Domiano and Roth, 19891, alcohols (Lyon and Jakoby, 19801, amines (Ramaswamy and Jakoby, 1987a), estrone and steroids (Adams and McDonald, 1981;Hobkirk et al, 1989), cholesterol (Epstein et al, 1984), and bile salts (Barnes et al, 1986). This study is focused on the phenol, or aryl, sulfotransferase (PST) as expressed in a bovine airway cell culture system.…”

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confidence: 99%

Regulation of phenol sulfotransferase expression in cultured bovine bronchial epithelial cells by hydrocortisone

Beckmann

Illig

Bartzatt

1994

Journal Cellular Physiology

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One conjugative pathway for the inactivation of endogenous and exogenous hydroxylated aromatic compounds is catalyzed by phenol (aryl) sulfotransferases (PSTs), which esterify phenolic acceptors with sulfate. The tracheobronchial epithelium is commonly exposed to phenolic drugs and pollutants, and metabolic sulfation and PST activity in this tissue have been previously demonstrated. To determine what factors may control PST expression, extracts of serum-free, growth factor-supplemented cultures of bovine bronchial epithelial cells were assayed for PST activity and PST antigen. The most significant finding was dose-dependent, apparent stimulated expression by hydrocortisone (EC50 = 4 nM, maximal stimulation at 20 nM). Time-course experiments, however, revealed progressive loss of PST in the absence of corticosteroid. After decay of extant PST in steroid-free medium, hydrocortisone reinduced the expression of PST three to fivefold. Western blots using mouse anti-bovine PST revealed corresponding increases in 32 kDa PST protein levels in response to hydrocortisone. Steady state kinetic analyses indicated apparent Km values of 1-3 microM for 2-naphthol regardless of culture conditions. These results suggest that detoxification of phenolic compounds by sulfation may be regulated by corticosteroids.

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Enzymic synthesis of steroid sulphates XIV. Properties of human adrenal steroid alcohol sulphotransferase

Cited by 21 publications

References 10 publications

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1

Dehydroepiandrosterone Sulfotransferase Localization in Human Adrenal Glands: A Light and Electron Microscopic Study*

Regulation of phenol sulfotransferase expression in cultured bovine bronchial epithelial cells by hydrocortisone

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