The Primate Adrenal Zona Reticularis is Defined by Expression of Cytochrome b5, 17α-hydroxylase/17,20-lyase Cytochrome P450 (P450c17) and NADPH-Cytochrome P450 Reductase (reductase) but not 3β-Hydroxysteroid Dehydrogenase/Δ5-4 Isomerase (3β-HSD)

Biochemical studies suggest that 17,20-lyase activity, and thus efficient synthesis of androgens by human P450c17, requires both reductase and the accessory protein cytochrome b5. Since the human and primate zona reticularis (ZR) secrete androgens, the expression of these proteins, and of 3β-HSD, was investigated by immunocytochemistry in the adrenal cortex of the mature rhesus macaque. Cytochrome b5 expression was restricted to the cells of the ZR which appeared deficient in 3β-HSD. However, both P450c17 and reductase were evident throughout the zona fasciculata. These data provide essential evidence in support of a functional role for cytochrome b5 in the regional control of 17α-hydroxylase and 17,20-lyase activities of P450c17 and thereby adrenal C19 steroid secretion by the primate adrenal gland.

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The Primate Adrenal Zona Reticularis is Defined by Expression of Cytochrome b5, 17 -hydroxylase/17,20-lyase Cytochrome P450 (P450c17) and NADPH-Cytochrome P450 Reductase (reductase) but not 3 -Hydroxysteroid Dehydrogenase/ 5-4 Isomerase (3 -HSD)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.84.9.3382 ◽

1999 ◽

Vol 84 (9) ◽

pp. 3382-3385 ◽

Cited By ~ 21

Author(s):

S. Mapes

Keyword(s):

Cytochrome P450 ◽

Cytochrome B5 ◽

Hydroxysteroid Dehydrogenase ◽

Cytochrome P450 Reductase ◽

Zona Reticularis ◽

Nadph Cytochrome ◽

P450 Reductase ◽

Nadph Cytochrome P450 Reductase

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Gender and gonadal status differences in zona reticularis expression in marmoset monkey adrenals: Cytochrome b5 localization with respect to cytochrome P450 17,20-lyase activity

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2006.12.023 ◽

2007 ◽

Vol 265-266 ◽

pp. 93-101 ◽

Cited By ~ 20

Author(s):

J. Christina Pattison ◽

Wendy Saltzman ◽

David H. Abbott ◽

Brynn K. Hogan ◽

Ann D. Nguyen ◽

...

Keyword(s):

Cytochrome P450 ◽

Cytochrome B5 ◽

Zona Reticularis ◽

Marmoset Monkey ◽

Lyase Activity ◽

Status Differences ◽

Gonadal Status

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Functional Aspects of Protein-Protein Interactions of Cytochrome P450 Cytochrome b5 and Cytochrome P450 Reductase

Molecular Aspects of Monooxygenases and Bioactivation of Toxic Compounds ◽

10.1007/978-1-4684-7284-4_11 ◽

1991 ◽

pp. 185-198 ◽

Cited By ~ 1

Author(s):

John B. Schenkman

Keyword(s):

Cytochrome P450 ◽

Protein Interactions ◽

Cytochrome B5 ◽

Cytochrome P450 Reductase ◽

Protein Protein Interactions ◽

P450 Reductase ◽

Functional Aspects

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Reduction of cytochrome b5 by NADPH–cytochrome P450 reductase

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2005.06.019 ◽

2005 ◽

Vol 440 (2) ◽

pp. 204-211 ◽

Cited By ~ 56

Author(s):

F. Peter Guengerich

Keyword(s):

Cytochrome P450 ◽

Cytochrome B5 ◽

Cytochrome P450 Reductase ◽

Nadph Cytochrome ◽

P450 Reductase ◽

Nadph Cytochrome P450 Reductase

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Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-2864 ◽

2016 ◽

Vol 101 (12) ◽

pp. 4585-4593 ◽

Cited By ~ 17

Author(s):

Juilee Rege ◽

Shigehiro Karashima ◽

Antonio M. Lerario ◽

Joshua M. Smith ◽

Richard J. Auchus ◽

...

Keyword(s):

Cytochrome B5 ◽

Serum Levels ◽

Dehydroepiandrosterone Sulfate ◽

Zona Fasciculata ◽

Adrenocortical Cells ◽

Normal Children ◽

Age Related ◽

Age Dependent ◽

Lyase Activity ◽

Liquid Chromatography Tandem Mass

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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