Corticosteroids in human blood: IX. Evidence for adrenal secretion of sulfate-conjugated cortisol, 11β,17α-dihydroxy-4-pregnene-3,20-dione-21-yl-sulfate
Abstract
A method was developed for the estimation of levels of cortisol-21-sulfate (F KS), cortisone-21-sulfate (ES), and 20(alpha + beta)-reduced cortisol-21-sulfates in blood plasma. Levels of these conjugates were determined in peripheral vein plasma of 42 normal subjects, 21 men, and 21 women (age range 20-64 years) and in adrenal vein plasma of patients with various adrenocortical disorders, six patients with primary hyperaldosteronism, five patients with Cushing's syndrome, and in two obese patients, suspected to have Cushing's syndrome, but with inconclusive laboratory findings. Adrenal vein blood was obtained by percutaneous, trans-femoral adrenal vein catheterization. Levels of non-conjugated (free) cortisol were determined in all plasma samples along with those of the sulfated steroids. F kappa S was found in all plasma samples, both in men and women. The variation in F kappa S levels paralleled that in the free cortisol levels, thus the ratio of F kappa/F kappa S was the same in the blood samples drawn at 8 AM as in those drawn at 4 PM or 5 PM (ranges: 17.5-36.3 in men, 23.6-45.8 in women). The levels of F kappa S were relatively lower in women than in men (women 610-880 ng/100 mL at AM, 300-510 ng/100 mL at PM; men: 760-1,220 ng/100 mL at AM, 380-760 ng/100 mL at PM). Plasma levels of total sulfate-conjugated delta 4-3-keto-C-21 steroids (F kappa S + E kappa S + 20(alpha+beta)-dihydrocortisol-21-sulfates) were 30-40% higher than those of the levels of cortisol-21-sulfate alone (separated by thin-layer chromatography). In the adrenal vein plasma, levels of delta 4-3-keto-C-21-steroid-21-yl sulfates were 20 to 40 times higher than levels of these steroids in the peripheral blood. The bulk of the steroid sulfate measured in the adrenal vein plasma consisted of cortisol-21-sulfate. The ratio of F kappa/F kappa S in the adrenal vein plasma was markedly smaller than in the peripheral vein plasma; it was 6.9-12.3 in males and 4.9-6.7 in females, whereas in the peripheral vein of the same subjects it was 19.2-43.7 in males and 21.4-48.3 in females. Cortisol-21-sulfate isolated from adrenal vein plasma was identified by mass spectrometry. The data presented provide evidence for the secretion of this conjugate by the adrenal cortex. Its secretion appears to be markedly elevated in patients with Cushing's syndrome, both due to hyperplasia and due to adrenal adenoma, as compared with normal subjects and patients with primary aldosteronism, both males and females. However, the F kappa/F kappa S ratio was markedly lower in Cushing's patients due to adrenal adenoma than due to adrenal hyperplasia, this suggesting that ACTH is stimulating intra-adrenal hydrolysis of cortisol sulfate.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some steroids can directly undergo phase 2 metabolism without being subjected to a phase 1 reaction, e.g. testosterone can be directly conjugated at its 17β-hydroxy group and corticosteroids through 21-sulfation.
“Additionally, some steroids can directly undergo phase 2 metabolism without being subjected to a phase 1 reaction, e.g. testosterone can be directly conjugated at its 17β-hydroxy group and corticosteroids through 21-sulfation [90].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [90]
Cites
Mass spectrometry in the diagnosis of steroid-related disorders and in hypertension research
Shackleton, C. H. L. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90132-g · Cited by 247 · see citing works
Self-citationBaulieu, E. E., Corpechot, C., DRAY, F., Emiliozzi, R., Lebeau, M., MAUVAIS-JARVIS, P., & Röbel, P. (1965) · PubMed · Cited by 180 · see citing works
Kornel, L. (1965) · Biochemistry · doi:10.1021/bi00879a011 · Cited by 60 · see citing works
Self-citationStudies on high affinity binding of mineralo-and glucocorticoids in rabbit aorta cytosol
Kornel, L., Kanamarlapudi, N., Travers, T., Taff, D. J., Patel, N., Chen, C., Baum, R. M., & Raynor, W. J. (1982) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(82)90173-x · Cited by 54 · see citing works
Self-citationSchweitzer, M., Branchaud, C. L., & Giroud, C. J. P. (1969) · Steroids · doi:10.1016/s0039-128x(69)80045-0 · Cited by 48 · see citing works
Kornel, L., Starnes, W. R., Hill, S. R., & HILL, A. (1969) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-29-12-1608 · Cited by 48 · see citing works
Self-citationBiosynthesis of Dehydroisoandrosterone Sulfate by Human Adrenocortical Tissue
Wallace, E. Z., & Lieberman, S. (1963) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-23-1-90 · Cited by 42 · see citing works
Kornel, L., Miyabo, S., SAITO, Z., CHA, R.-W., & WU, F.-T. (1975) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-40-6-949 · Cited by 35 · see citing works
Self-citationCorticosteroid 21-sulphates in human urine
Pasqualini, J. R., & Mf, J. (1961) · Biochemical Journal · doi:10.1042/bj0810147 · Cited by 33 · see citing works
Studies on the Metabolism of Pregnenolone Sulfate1
Calvin, H. I., & Lieberman, S. (1966) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-26-4-402 · Cited by 24 · see citing works
Kornel, L. (1963) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-23-12-1192 · Cited by 22 · see citing works
Self-citationMiyabo, S., & Kornel, L. (1974) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(74)90137-x · Cited by 19 · see citing works
Self-citationKornel, L., Miyabo, S., & Takeda, R. (1971) · PubMed · Cited by 19 · see citing works
Self-citationNáray‐Fejes‐Tóth, A., Rusvai, E., & Fejes‐Tóth, G. (1994) · Endocrinology · doi:10.1210/endo.134.4.8137730 · Cited by 17 · see citing works
Singer, S. S., Hess, E., & Sylvester, S. (1977) · Biochemical Pharmacology · doi:10.1016/0006-2952(77)90240-4 · Cited by 15 · see citing works
Kornel, L., & Motohashi, K. (1965) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-25-7-904 · Cited by 15 · see citing works
Self-citationAspects of Corticosteroid Biogenesis and Metabolism during the Perinatal Period
GIROUD, C. J. P. (1971) · Clinical Obstetrics & Gynecology · doi:10.1097/00003081-197109000-00007 · Cited by 14 · see citing works
Corticosterone Sulfation by Livers of Normal and Hypertensive Rats1
Turcotte, G., & Silah, J. G. (1970) · Endocrinology · doi:10.1210/endo-87-4-723 · Cited by 14 · see citing works
HAYASHI, T., & Kornel, L. (1990) · Endocrinology · doi:10.1210/endo-126-1-307 · Cited by 13 · see citing works
Self-citationKornel, L., & Miyabo, S. (1975) · Steroids · doi:10.1016/0039-128x(75)90034-3 · Cited by 12 · see citing works
Self-citationAn improved rapid method for free and conjugated 17-hydroxycorticosteroids in plasma.
Kornel, L. (1959) · PubMed · Cited by 11 · see citing works
Self-citationStudies on Steroid Conjugates: V. Urinary 17-Hydroxycorticosteroids in Essential Hypertension1
Kornel, L., & TAKEDA, R. (1967) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-27-2-233 · Cited by 10 · see citing works
Self-citationNew paper chromatographic systems for the separation of conjugated corticosteroids
Kornel, L., Miyabo, S., & Saito, Z. (1975) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)80163-1 · Cited by 10 · see citing works
Self-citationNáray‐Fejes‐Tóth, A. (1994) · Endocrinology · doi:10.1210/en.134.4.1671 · Cited by 5 · see citing works
Corticosteroid sulfate excretion and estrogen receptors in breast cancer
Rose, D. P., & Liskowski, L. (1976) · Clinica Chimica Acta · doi:10.1016/0009-8981(76)90258-8 · Cited by 3 · see citing works
Stančáková, A., & Klimesová, Z. (1979) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450 · see citing works
Self-citationPalermo, M., Gomez-Sanchez, C., Roitman, E., & Shackleton, C. H. L. (1996) · Steroids · doi:10.1016/s0039-128x(96)00118-9 · Cited by 70 · see citing works
Self-citationExaggerated adrenarche and altered cortisol metabolism in Type 1 diabetic children
Remer, T., Maser‐Gluth, C., Boye, K. R., Hartmann, M. F., Heinze, E., & Wudy, S. A. (2006) · Steroids · doi:10.1016/j.steroids.2006.02.005 · Cited by 38 · see citing works
- Authors
- Kornel, L., Patel, S. K., Ezzeraimi, E., & Shackleton, C. H. L.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- Kornel, Ludwig
- ORCID
- Patel, Suresh K.
- Venue
- Steroids
- Publisher
- Elsevier BV
- Published
- 1995-12
- Volume
- 60
- Issue
- 12
- Pages
- 817-823
- ISSN
- 0039-128X (ISSN-L)
- OpenAlex
- W2055347789
- Cited by
- 3
- References
- 25
- Citations by year
- 2019: 1
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Steroids (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk034400-10, 1s10rr006505-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-34400)
- National Center for Research Resources (RR06505)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- adrenal steroid secretion, free cortisol, adrenal disorders, primary aldosteronism, Cushing's syndrome
- MeSH terms
- Adrenal Cortex Diseases, Adrenal Cortex Hormones, Adrenal Glands, Adult, Cushing Syndrome, Female, Humans, Hydrocortisone, Hyperaldosteronism, Male, Middle Aged, Obesity, Reference Values, Sex Characteristics, Veins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review