BIOSYNTHESIS OF 11β-Hydroxyandrostenedione BY HUMAN AND BABOON ADRENALS

Axelrod, Leonard R.; Kraemer, D.C.; Burdett, James E.; Goldzieher, Joseph W.

doi:10.1530/acta.0.0720545

Cited by 25 publications

(9 citation statements)

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“…The levels of 11 β OHA, a rarely assayed androgen that originates mainly from 11 β -hydroxylation of A [ 29 ], showed a very close correlation with levels of A ( r s = 0.993). Given that 11 β OHA is also produced from cortisol [ 30 ], we suggest that 21DF may also contribute to the formation of this 11 β -hydroxylated androgen in CAH21.…”

Section: Discussionmentioning

confidence: 98%

A Liquid Chromatography/Tandem Mass Spectometry Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia

Fiet

Bouc

Guéchot

et al. 2017

Journal of the Endocrine Society

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Context:Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (CAH21) is most often diagnosed by newborn screening. The classic parameter studied is 17-hydroxy-progesterone, but the positive predictive value for the diagnosis of CAH is low in full-term newborns and even lower in preterm newborns.Objective:To evaluate the diagnostic utility of simultaneously quantifying a large number of steroids by using liquid chromatography/tandem mass spectrometry (LC-MS/MS) from a small serum volume in patients with CAH, particularly during the neonatal period.Setting and participants:LC-MS/MS was applied to sera from patients with CAH who had a classic form (n = 48) and rare forms (n = 2) of 21-hydroxylase deficiency, normal preterm (n = 10) and normal full-term (n = 20) neonates, and young patients without CAH (non-CAH; n = 149) but with various other diseases (delayed or advanced puberty, hirsutism, pubarche, adrenarche, simple growth retardation).Methods:Sixteen steroids (glucocorticoids, mineralocorticoids, androgens, Δ5-steroids) were analyzed in 150 µL of serum by LC-MS/MS.Results:An LC-MS/MS serum steroid profile was developed and validated to provide a reliable etiologic diagnosis of CAH. The serum levels of 17OH-progesterone and 21 deoxycortisol in non-CAH are reported, along with the rarely assayed 21-deoxycorticorticosterone and 11β hydroxy Δ4-androstenedione, which will aid in the diagnosis of CAH21. In addition, serum levels of mineralocorticoids, androgens, and Δ5-steroids allowed investigation of other forms of CAH.Conclusion:This steroid LC-MS/MS approach on a small serum volume is well suited for pediatrics, particularly neonatal medical practice, to aid in the diagnosis and monitoring of various forms of CAH.

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Section: Discussionmentioning

confidence: 98%

A Liquid Chromatography/Tandem Mass Spectometry Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia

Fiet

Bouc

Guéchot

et al. 2017

Journal of the Endocrine Society

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“…The synthesis of 11OHAD occurs predominately in the adrenal gland from AD (Figure 1), through the action of steroid 11β-hydroxylase (CYP11B1), and small amounts might be produced from cortisol 24 . Consistent with previous reports that measured only 11OHAD 25, 26 , we found negligible amounts of all 11oxC19 steroids in sera from patients with 11OHD, which confirms that their synthesis relies on CYP11B1.…”

Section: Discussionmentioning

confidence: 99%

Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency

Turcu

Nanba

Chomic

et al. 2016

European Journal of Endocrinology

175

170

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Objective To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insight to the mechanisms of their formation. Design Serum samples were obtained from 38 patients (19 men) with classic 21OHD, age 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n=5) and 21OHD adrenal tissue (n=3) was used for immunohistochemical studies. Methods We measured 11 steroids in all sera using liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. Results Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, p< 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in adrenal vein than in inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in sera from patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. Conclusions All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess.

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“…The measurement of 21deoxycortisol(21DF) in response to ACTH has been advocated by a number of authors (Franks, 1974;Milewicz et al, 1984) as a more sensitive marker of the heterozygote state than the response of 17~-OH-progesterone (1 7Po). What these authors do not draw out is the particular significance of 21DF as the I ID-hydroxylated metabolite of 17Po which, in women with normal ovaries, almost certainly represents a pure adrenal compound, since very little I 10-hydroxylase activity is found in normal ovarian tissue (Axelrod et al, 1973). There is a suggestion, however, that polycystic ovaries may have some intrinsic 1 IB-hydroxylase activity (Maschler et af., 1975;Polson et al, 1986;Owen et al, 1988), while inhibition of 1 10-hydroxylation by androgen has been previously demonstrated (Baird et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Steroid Responses to Acth in Women With Polycystic Ovaries

Hague

Honour

Adams

et al. 1989

Clinical Endocrinology

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Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

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BIOSYNTHESIS OF 11β-Hydroxyandrostenedione BY HUMAN AND BABOON ADRENALS

Cited by 25 publications

References 0 publications

A Liquid Chromatography/Tandem Mass Spectometry Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia

A Liquid Chromatography/Tandem Mass Spectometry Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia

Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency

Steroid Responses to Acth in Women With Polycystic Ovaries

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