Urinary Steroids Profile
Urinary Steroids are measured on the 24h urines. Aim of the test is to provide information about steroid hormones metabolism
The absolute range of single metabolite looks too large, but in some way this hormonal pattern may be representative of people individuality.
In the female, Estradiol (E2) is the major biologically active hormone, whereas it is Testosterone (T) in the male. Compounds in brackets {} are intermediates not assayed in urine. Progesterone(P) is metabolized
to Pregnanediol (PD) in the liver. P is not normally excreted in urine in measurable quantities and Pregnanediol (PD) as measured in urine reflects Progesterone levels both sensitively and accurately.
Age and sex dependance ??
What about the ratios between metabolites or groups of metabolites to identify regulatory steps (enzymes)? See G6PD
Steroids Hormones Details
To access full information on steroid hormones use Full Metabolome Database
Steroids hormones metabolic pathways
Kegg Pathways is as metabolic pathways network allowing fast access to metabolites and enzymes description.
Kegg Pathways-Steroid hormone metabolism - Homo sapiens
Annotated Kegg Pathways-Steroid hormone metabolism
Normal Ranges 2006
Cortisol/cortisone
Cortisol catabolism
5a-Tetrahydrocortisol (HMDB00526) and H4Cortisone/H4Cortisol
Tetrahydrocortisone
Tetrahydrocortisol function
Tetrahydrocortisol
The cortisol metabolite, 20β-dihydrocortisol, has very little glucocorticoid activity, but shows significant angiostatic activity in the CAM comparable to cortisol and Tetrahydrocortisol even more.
Tetrahydrocortisol synthesis depends on the activity of the enzyme 3-alpha hydroxysteroid dehydrogenase that belongs to the Group of xenobiotics inducible CYP450
11beta-hydroxysteroide dehydrogenases
- Quinkler M, Zehnder D, Lepenies J, Petrelli MD, Moore JS, Hughes SV, Cockwell P, Hewison M, Stewart PM: Expression of renal 11beta-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function. Eur J Endocrinol. 2005 Aug;153(2):291-9. [PubMed Link Image]
- Rosler A, Leiberman E, Rosenmann A, Ben-Uzilio R, Weidenfeld J: Prenatal diagnosis of 11beta-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1979 Oct;49(4):546-51. [PubMed Link Image]
Ann Endocrinol (Paris). 2007 Oct;68(5):349-56. Epub 2007 Mar 26.
[11beta-hydroxysteroide dehydrogenases. Recent advances]
[Article in French]
Vantyghem MC, Marcelli-Tourvieille S, Defrance F, Wemeau JL.
Service d'endocrinologie et métabolisme, clinique d'endocrinologie Marc-Linquette, 6, rue du Professeur-Laguesse, CHRU de Lille, 59037 Lille cedex, France. mc-vantyghem@chru-lille.fr
11beta-hydroxysteroide dehydrogenase (11beta-OHSD) enzymes exhibit a regulating action upon cortisol metabolism before access to its receptors. Two types of isoenzymes have been described, type 2 being the most anciently known. Type 2 11beta-OHSD, which changes cortisol into cortisone, is a unidirectional dehydrogenase mainly located in kidney, that protects mineralocorticoid receptors from illicit activation by glucocorticoids. Mutations of the gene coding for this enzyme has been demonstrated in apparent mineralocorticoid excess, which induces hypertension and hypokalemia with low renin and aldosterone levels. Polymorphisms of this gene could modulate essential hypertension and also be responsible for certain forms of acquired apparent mineralocorticoid excess especially after liquorice intoxication, in hypothyroidism, Cushing syndrome, and chronic renal insufficiency. Type 1 11beta-OHSD, which changes cortisone into cortisol, is a reductase, mainly located in liver and adipose tissue. Functional defects of this enzyme have been shown in polycystic ovaries and cortisone reductase deficiency. By contrast, metabolic syndrome, corticoid-induced osteoporosis, and glaucoma are linked to a local over-activity of this enzyme. The understanding of action mechanisms of these two enzymes currently leads to 11beta-OHSD inhibitors development, therefore opening new therapeutic strategies, especially in metabolic syndrome.
What can be expected with ACE inhibitors and similar drugs ??
21-HYDROXYLASE DEFICIENCY
Metabolism Figure
Dignostic Ratios
ET/AN
Inverse correlation with steroid-5-alpha-reductase, the enzyme responsible for the synthesis of
Dihydrotestosterone - DHT and brain neurosteroids
Androstanediol glucuronide 3α-Androstanediol glucuronide (3α-ADG) is a metabolite formed from human androgens and has been proposed as means of measuring androgenic activity.
In women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone are the major precursors of plasma 3α-ADG, accounting for almost the totality of circulating 3α-ADG. Levels of 3α-ADG decrease significantly with age.
3α-ADG is used as a marker of target tissue cellular action. 3α-ADG correlates with level of 5α-reductase activity (testosterone and 3α-androstanediol to dihydrotestosterone) in the skin. Concentrations of 3α-ADG are associated with the level of cutaneous androgen metabolism.
ET/AN and homosexuality
ET/AN is higher in male homosexuals
- Androsterone/Etiocholanolone Ratios in Male Homosexuals, 1973
- A role for 5alpha-reductase activity in the development of male homosexuality? 2004 Ann N Y Acad Sci. 2004 Dec;1032:237-44.
Higher body hair with lower mesmorphism ratings were observed in Caucasian homosexual men compared with the general male population, reflecting elevated 5alpha-reductase (5alphaR) activity, and higher dihydrotestosterone-to-testosterone (DHT-to-T) ratio, in sharp contrast to 46,XY 5alphaR 2 deficiency subjects, who are often born with ambiguous, or female genitalia, but tend to grow up to be muscular, heterosexual men with very little body hair, or beard. One study also showed them scoring around dull normal IQs. A greater prevalence of liberal body hair growth in men with higher IQs and/or educational levels was also observed in several samples. The exceptions to this statistical trend are too unsettling, however. Nevertheless, the results of a number of published studies, including one showing higher DHT-to-T ratio in homosexual men, done with different objectives over a span of 80 years, together strongly support these findings. Furthermore, in an animal model, "cognitive-enhancing effects" of "5alpha-reduced androgen [metabolites]" were recently demonstrated. ( contradictory )
Urinary steroid measurements in some endocrine and psychiatric diseases. 2005
A deeper insight
1. Mune T, White PC: Apparent mineralocorticoid excess: genotype is correlated with biochemical phenotype. Hypertension. 1996 Jun;27(6):1193-9. [PubMed Link Image]
2. Weykamp CW, Penders TJ, Schmidt NA, Borburgh AJ, van de Calseyde JF, Wolthers BJ: Steroid profile for urine: reference values. Clin Chem. 1989 Dec;35(12):2281-4. [PubMed Link Image]
4. Koren W, Grienspuhn A, Kuznetsov SR, Berezin M, Rosenthal T, Postnov YV: Enhanced Na+/H+ exchange in Cushing's syndrome reflects functional hypermineralocorticoidism. J Hypertens. 1998 Aug;16(8):1187-91. [PubMed Link Image]
7. Rapetti S, Francia G, Iacono C, Martignoni G, Contessi G, Brunelli M, Galvanin F, Serio G: An unusual case of Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia. Chir Ital. 2003 Mar-Apr;55(2):235-41. [PubMed Link Image]
8. Melander O, Frandsen E, Groop L, Hulthen UL: No evidence of a relation between 11beta-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity. Am J Hypertens. 2003 Sep;16(9 Pt 1):729-33. [PubMed Link Image]
9. Panin LE, Tuzikov FV, Gimautdinova OI: Tetrahydrocortisol-apolipoprotein A-I complex specifically interacts with eukaryotic DNA and GCC elements of genes. J Steroid Biochem Mol Biol. 2003 Dec;87(4-5):309-18. [PubMed Link Image]
10. Shackleton C, Malunowicz E: Apparent pregnene hydroxylation deficiency (APHD): seeking the parentage of an orphan metabolome. Steroids. 2003 Oct;68(9):707-17. [PubMed Link Image]
Etiocholanolone and fever
Papers Etiocholanolone fever
Pregnenetriol
alpha-androstane-diol
Testosterone inactive metabolite by the action of 3alpha-hydroxysteroid 3-dehydrogenase
Low levels may depend on low testosterone synthesis or low 5-alpha- reductase activity
THE OCCURRENCE OF 3-ALPHA, 21-DIHYDROXYPREGNANE, 11-20-DIONE (TETRAHYDRO COMPOUND A) IN THE SERUM OF CHILDREN 1957
High THS may depend on high activity of 3alpha-hydroxysteroid 3-dehydrogenase (see whole metabolism)
Quetzal:tetrahydro compound S
human aldo-keto reductase family 1 member C4 induction
Haplotype analysis of the aldosterone synthase (CYP11B2) and 11beta-hydroxylase gene (CYP11B1) locus, 2005
Tetrahydrodeoxycortisol??
CYP11B1??
CYP11B2?
Effect of angiostatic steroid with or without glucocorticoid activity on metastasis. 1987
The effect of angiostatic steroids on pulmonary metastasis was investigated using mice treated with such a steroid before or after intravenous inoculation with Lewis lung carcinoma; cortisone acetate and tetrahydro S, of which the former possesses glucocorticoid activity, and the latter lacks it, were used as the angiostatic steroids. In the presence of heparin, both types of steroids prevented angiogenesis in chick embryo and also pulmonary metastasis in mice when the administration started after cell lodgement. On the other hand, one-shot cortisone treatment before cell inoculation increased the weight of lung colonies to twice that seen in the controls, while tetrahydro S pretreatment did not enhance metastasis. These results revealed that both angiostatic steroids with and without glucocorticoid activity in the presence of heparin inhibited tumor growth in the lungs, and further indicated that cortisone acetate affected the steps of metastasis after the invasion of tumor cells into the blood stream until angiogenesis in the secondary foci, and consequently promoted metastasis, whereas tetrahydro S (which has no glucocorticoid activity) did not affect the steps before angiogenesis. It was thus indicated that the inhibitory effect of angiostatic steroids against tumor growth due to an anti-angiogenic activity was not dependent at all on the metastasis promotion by these steroids having glucocorticoid activity.
Genetic variation at the locus encompassing 11-beta hydroxylase and aldosterone synthase accounts for heritability in cortisol precursor (11-deoxycortisol) urinary metabolite excretion. 2004
There was strong evidence for association between polymorphisms of both CYP11B1 and CYP11B2 and urinary THS, which was strongest for the CYP11B1 exon 1 polymorphism (P = 0.00002).
Tetrahydrodeoxycortisol
Analytical Method
additional info from the lab
from other labs...
Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. 2011
Lab prof. Marco Vincenti
It is interesting to note that among the eight identified compounds, five (63%) are involved in steroidal biosynthesis, confirming their potential in the detection and diagnosis of PCa. Similarly, Choi et al. found elevated levels of 16-hydroxy-dehydroepiandrosterone, epiandrosterone, etiocholanolone, and pregnanetriol in patients diagnosed with papillary thyroid carcinoma [27]. The first steroid appears to also be overexpressed in the present case for patients with PCa, but pregnanetriol was underexpressed in the same patients and epiandrosterone was found in comparable concentrations in the two populations. Dehydroepiandrosterone is involved in the expression of insulin-like growth factor 1, whose dysregulation is implicated in certain colon, liver, prostate, and breast cancers [28]. This observation may justify the inclusion of 16-hydroxy-dehydroepiandrosterone among the potential biomarkers for PCa. Pregnanetriol, together with 5 β-pregnanediol, is also known to be dysregulated in adrenal syndromes, such as adrenal tumors or Cushing’s syndrome [29,30]. Increased androsterone levels were found in a cohort of PCa-affected individuals within a multivariate investigation of the urinary steroidal profile, and the present findings are in accordance with our previous study [16]. Other steroids that proved useful to discriminate PCa from BPH Metabolic alteration of urinary steroids in pre- and post-menopausal women, and men with papillary thyroid carcinoma, 2011 were possibly overlooked in the present untargeted selection because of their low concentration in urine.
Untargeted Metabolomic Profile for the Detection of Prostate Carcinoma—Preliminary Results from PARAFAC2 and PLS–DA Models, 2019
