Type 5 17β-Hydroxysteroid Dehydrogenase (AKR1C3) Contributes to Testosterone Production in the Adrenal Reticularis

Nakamura, Yasuhiro; Hornsby, Peter J.; Casson, Peter R.; Morimoto, Ryo; Satoh, Fumitoshi; Xing, Yewei; Kennedy, Michael R.; Sasano, Hironobu; Rainey, William E.

doi:10.1210/jc.2008-2374

Cited by 111 publications

(62 citation statements)

References 28 publications

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“…qPCR analysis also revealed increased expression of Sult1e1, which can be involved in DHEA sulfation (26) (Figure 2D). Taken together, decreased expression of HSD3B (HSD3B2 in humans, HSD3B1 in mice), expression of CYP17 and CYB5 (its allosteric regulator), and expression of the potential for steroid sulfation are reminiscent of the human zR (5,(27)(28)(29)(30)(31)(32). To investigate the functional capacity of these putative zR-like cells, we analyzed concentrations of steroids relying on CYP17 activity ( Figure 2F).…”

Section: Fl/+mentioning

confidence: 99%

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

Dumontet¹,

Sahut‐Barnola²,

Septier³

et al. 2018

JCI Insight

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Section: Fl/+mentioning

confidence: 99%

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

Dumontet¹,

Sahut‐Barnola²,

Septier³

et al. 2018

JCI Insight

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“…The adrenals secrete small amounts of testosterone but greater amounts of androstenedione through the action of CYP11A1, HSD3B2 and 17-hydroxysteroid dehydrogenase (an aldo-keto reductase, AKR1C3). 19 The gonads also produce 17-OHP and high concentrations of 17-OHP can be found for example in ovarian follicles. 20 17-OHP may also be converted to DHT through a 'backdoor path'.…”

Section: Steroid Synthesismentioning

confidence: 99%

17-Hydroxyprogesterone in children, adolescents and adults

Honour

2014

Ann Clin Biochem

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17-Hydroxyprogesterone (17-OHP) is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase. An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentrations of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotrophic hormone. The classical congenital adrenal hyperplasia (CAH) presents usually with virilisation of a girl at birth. Affected boys and girls can have renal salt loss within a few days if aldosterone production is also compromised. Diagnosis can be delayed in boys. A non-classical form of congenital adrenal hyperplasia (NC-CAH) presents later in life usually with androgen excess. Moderately raised or normal 17-OHP concentrations can be seen basally but, if normal and clinical suspicion is high, an ACTH stimulation test will show 17-OHP concentrations (typically >30 nmol/L) above the normal response. NC-CAH is more likely to be detected clinically in females and may be asymptomatic particularly in males until families are investigated. The prevalence of NC-CAH in women with androgen excess can be up to 9% according to ethnic background and genotype. Mutations in the 21-hydroxylase genes in NC-CAH can be found that have less deleterious effects on enzyme activity. Other less-common defects in enzymes of cortisol synthesis can be associated with moderately elevated 17-OHP. Precocious puberty, acne, hirsutism and subfertility are the commonest features of hyperandrogenism. 17-OHP is a diagnostic marker for CAH but opinions differ on the role of 17OHP or androstenedione in monitoring treatment with renin in the salt losing form. This review considers the utility of 17-OHP measurements in children, adolescents and adults.

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“…Consequently, in women, DHEAS concentration is relatively stable throughout the day (82). DHEAS is the precursor of active androgens and can be taken up by ovarian follicles to synthesize testosterone (83) and even converted into dihydrotestosterone in peripheral tissues once converted to androstenedione, without requiring prior formation of testosterone (84).…”

Section: Adrenal Androgen Excess Investigationmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

Pugeat

Plotton

Perrière

et al. 2018

European Journal of Endocrinology

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Measuring total testosterone level is the first-line approach in assessing androgen excess in women.The main pitfalls in measuring testosterone relate to its low concentration and to the structural similarity between circulating androgens and testosterone, requiring accurate techniques with high specificity and sensitivity. These goals can be achieved by immunoassay using a specific antitestosterone monoclonal antibody, ideally after an extraction step. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) will be commonly used for measuring testosterone, providing optimal accuracy with a low limit of detection. Yet, the pitfalls of these two techniques are well identified and must be recognized and systematically addressed. In general, laboratories using direct testosterone immunoassay and mass spectrometry need to operate within a quality framework and be actively engaged in external quality control processes and standardization, so as to ensure appropriate interpretation irrespective of the particular laboratory. Circulating testosterone is strongly bound to sex-hormone binding-globulin (SHBG), and SHBG levels are typically low in overweight hyperandrogenic patients. Thus, low SHBG may decrease circulating testosterone to normal values, which will mask androgen excess status. One way to avoid this pitfall, awaiting direct free-testosterone assays that are yet to be developed, is to measure SHBG and calculate free testosterone. A few other pitfalls will be discussed in this review, including those of adrenal androgen exploration, with the aim of helping clinicians to better handle laboratory investigation of androgen excess disorders in women.

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Type 5 17β-Hydroxysteroid Dehydrogenase (AKR1C3) Contributes to Testosterone Production in the Adrenal Reticularis

Cited by 111 publications

References 28 publications

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

17-Hydroxyprogesterone in children, adolescents and adults

MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis

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