The Hormones of the Adrenal Cortex

Reichstein, T.; Shoppee, C. W.

doi:10.1016/s0083-6729(08)60260-5

Cited by 115 publications

(23 citation statements)

References 184 publications

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“…To this day, there is sometimes a careless misunderstanding about the distinction between the two compounds, and DOCA is occasionally used wrongly as an abbreviation for DOC itself. Astonishingly, Reichstein (1951) himself was not above (very infrequent) careless use of language, as in his published Nobel Lecture, in the statement 'desoxycorticosterone (I: referred to here as DOCA) '. The assumption appears to be that in vivo the acetate is rapidly hydrolysed by non-specific esterases to the free alcohol, and hence it is the latter that binds to the receptor.…”

Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

“…This appears to be because the synthetic route used by Steiger & Reichstein leads first to the acetate rather than to the free compound. Early on, Reichstein (1951). suggested that biologically there was no difference between the two, and for the benefit of a (slightly) simpler and cheaper synthesis, DOCA was made available.…”

Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

“…in the 1930s and 1940s, a wide variety of bioassays were in use. None of the groups that were involved in the isolation of adrenal steroids in the 1930s and 1940s, including those of Kendall and Reichstein, distinguished between 'glucocorticoids' and 'mineralocorticoids', and these terms were not used in either of the latter two groups' Nobel Lectures in 1950 (Kendall 1951, Reichstein 1951. Partly this could have been due to the fact that most of the steroids they isolated shared the same activities, which were already known to be of much wider physiological significance than suggested by these narrow terms.…”

Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

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The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

Vinson¹

2011

Journal of Endocrinology

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Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor activation, and, in particular, the relationship between steroid hormone structure and function remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak mineralocorticoid, while the addition of an 11b-hydroxyl group produces glucocorticoid activity, yet further hydroxylation at C18 leads to the most potent mineralocorticoid, aldosterone? This review aims to show that the field has been confused by the misreading of the earlier literature and that DOC, far from being relatively inactive, in fact has a wide range of activities not shared by the other corticoids. In contrast to the accepted view, the presence of an 11b-hydroxyl group yields, in corticosterone or cortisol, hormones with more limited functions, and also more readily regulated, by 11b-hydroxysteroid dehydrogenase. This interpretation leads to a more systematic understanding of structure-function relationships in the corticosteroids and may assist more rational drug design.

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Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

Section: Beginnings: Isolation and The Bioassay Of Corticosteroidsmentioning

confidence: 99%

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The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

Vinson¹

2011

Journal of Endocrinology

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“…3) The fluorescence of compounds F and B in sulfuric acid has been considered characteristic for these substances (13 The alpha-ketolic steroid metabolite (AKSF) excretion was approximated as described above. Lipid-soluble reducing substances (G'ase.…”

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confidence: 99%

Urinary Alpha-Ketolic Steroid Metabolites of Cortical Hormones Administered to Subjects With Adrenal Cortical Insufficiency 1

Richardson¹,

Touchstone²,

Dohan³

et al. 1955

J. Clin. Invest.

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The analysis of urinary excretory products following the administration of known compounds is one of the classical methods for the study of their metabolism. The developments in paper chromatographic (1) and micro-analytic (2) technics and the use of glucuronidase hydrolysis (3) have considerably decreased the difficulties of investigating steroid metabolism by this method. Using these newer technics, we have studied the urinary excretion pattern of the major alpha-ketolic steroids after the administration of the six "active" adrenal cortical steroids to individuals with severe adrenal cortical insufficiency. We have found, as has been demonstrated for other steroids (4), that the major alpha-ketolic metabolites result from the reduction in ring A of the steroid nucleus to the 3-alpha-hydroxy pregnane derivatives (the socalled "tetrahydro" form) and that the hydroxyl and ketone groups on carbon atom 11 are interconvertible for corticosterone and 1 1-dehydrocorticosterone as well as for hydrocortisone and cortisone. METHODS I. TerminologySince steroid terminology is varied and the proper chemical names consume considerable space, the terms and abbreviations more commonly used in physiological research will be employed in this paper. Definitions and abbreviations are listed below.Alpha-ketolic steroids: Pregnane derivatives having 20-keto and 21-hydroxy substituents (i.e., alpha-ketol group). A4-pregnene-21-ol-3, 11, 20-trione.DOC; li-desoxycorticosterone; A'-pregnene-21-ol-3, 20-dione. These are listed in order of decreasing polarity. The acetate is indicated by the abbreviation ac.Alpha-ketolic steroid metabolites (AKSM): Steroids with the alpha-ketolic side chain found in the urine. These are detectable by reaction of the alpha-ketol side chain with alkaline blue tetrazolium to produce a blue color. The unmodified abbreviation H4 indicates reduction in ring A to form the 3a normal (i.e., pregnane) reduction product. In addition to the alpha-ketolic cortical hormones, the major metabolites are: H4F; tetrahydro-hydrocortisone; pregnane-3a, 11P, 17a, 21-tetrol-20-one. H4E; tetrahydro-cortisone; pregnane-3a, 17a, 21-triol-11, 20-dione. H4S; tetrahydro-11-desoxy-17-hydroxycorticosterone; pregnane-3a, 17a, 21-triol-20-one. H,B; tetrahydro-corticosterone; pregnane-3a, Ilfi, 21-triol-20-one. H4A; tetrahydro-dehydrocorticosterone; pregnane-3a, 21-diol-11, 20-dione. H4DOC; tetrahydro-l1-desoxycorticosterone; pregnane-3ca, 21-diol-20-one. Polarity: In the chromatograms, the most polar steroids (i.e., those with the most hydroxyl and keto substituents) appear in the slowest moving fraction, X, and the least polar in the fastest moving fraction, Z. (See III, B Paper chromatographic and micro-analytic technics.) 285

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“…By l94J, twenty-eight steroids had been isolated in crystallille for.m from adrenocortical tissue (14). Of these, on1y six were bio1ogically active.…”

Section: Chemical Structure Of the Active Compoundsmentioning

confidence: 99%