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  • Title: Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate.
    Author: Rege J, Karashima S, Lerario AM, Smith JM, Auchus RJ, Kasa-Vubu JZ, Sasano H, Nakamura Y, White PC, Rainey WE.
    Journal: J Clin Endocrinol Metab; 2016 Dec; 101(12):4585-4593. PubMed ID: 27623070.
    Abstract:
    CONTEXT: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. OBJECTIVE: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. PARTICIPANTS AND METHODS: Δ5-steroid sulfates were quantified by liquid chromatography-tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5-18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2-35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. RESULTS: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. CONCLUSION: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.
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