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Cited by 219Adrenal Hormones and DisordersHormonal Regulation and HypertensionEstrogen and related hormone effects

The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase.

Endoh, A, Kristiansen, S B, Casson, P R, Buster, J E, Hornsby, P J·1996·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.81.10.8855801
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Abstract

Based on indirect evidence, it has often been assumed that the zona reticularis of the adult human adrenal cortex is the source of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), but direct tests of this concept have been few. Using the techniques of cell culture, Northern blotting, and RIA, we compared the properties of separated adult zonal cells to those of fetal zone cells, a cell type well known to secrete large amounts of DHEA(S) due to its low expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). In nine glands from donors of a wide age range, the zona fasciculata and zona reticularis were separated and dissociated, and the cells were placed in culture. After 5 days, serum was removed by a 24-h period in serum-free defined medium followed by a 24-h exposure to cAMP analogs, with the optional addition of insulin, also in serum-free medium. The separated fasciculata and reticularis cells showed large differences in the DHEA(S)/cortisol (F) production ratios from added pregnenolone precursor, consistent with the synthesis of only F and essentially no DHEA(S) by fasciculata cells and with the synthesis of mostly DHEA(S) with little or no F by both reticularis cells and fetal zone cells. The different patterns of steroidogenesis were accompanied by a much lower level of expression of type II 3 beta HSD in reticularis cells, similar to that in fetal zone cells. In contrast, other genes were similarly regulated in the two adult zones and in the fetal zone by both cAMP and insulin. The levels of messenger ribonucleic acids for 17 alpha-hydroxylase, cholesterol side-chain cleavage enzyme, 21-hydroxylase, and 11 beta-hydroxylase responded to cAMP and insulin in both reticularis cells and fetal zone cells in the same pattern as that previously established in fasciculata cells. The central role of the limited expression of 3 beta HSD in the DHEA(S)-synthesizing property of reticularis cells was established by inhibition of 3 beta HSD in fasciculata cells with trilostane, which caused them to increase their DHEA/F production ratio to a level exceeding even that in fetal zone cells. There did not appear to any age-related changes in gene expression that could account for the large age-related decline in DHEA(S) biosynthesis in humans in either reticularis or fasciculata cells. Thus, the most likely cause of the age-related decline in adrenal androgen biosynthesis is an age-related decline in the number of functional reticularis cells, without a major change in the differentiated properties of the zonal cells as a function of age.

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Crossref · 10.1210/jcem.81.10.8855801

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  • The abundance of 3βHSD protein in the zona reticularis appears to decrease with the onset of adrenarche, and the adrenal expression of cytochrome b5, which fosters the 17,20-lyase activity of P450c17, is almost exclusively confined to the zona reticularis; both of these factors strongly favor the production of DHEA.

    “The abundance of 3␤HSD protein in the zona reticularis appears to decrease with the onset of adrenarche (202,724,725), and the adrenal expression of cytochrome b 5 , which fosters the 17,20-lyase activity of P450c17, is almost exclusively confined to the zona reticularis (203, 205, 726); both of these factors strongly favor the production of DHEA (727).”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [202]

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Authors
Endoh, A., Kristiansen, S. B., Casson, P. R., Buster, J. E., & Hornsby, P. J.
Affiliations
Baylor College of Medicine (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1996-10
Volume
81
Issue
10
Pages
3558-3565
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.81.10.8855801
OpenAlex
W2148636250
Cited by
219
References
23
Citations by year
2025: 5 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 6
FWCI
6.91
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG 12287)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
zona reticularis, adrenal cortex, dehydroepiandrosterone, dehydroepiandrosterone sulfate, 3β-hydroxysteroid dehydrogenase, steroidogenesis, adrenal androgens, zona fasciculata, cAMP signaling, insulin, trilostane, 17α-hydroxylase, 21-hydroxylase, 11β-hydroxylase, cholesterol side-chain cleavage enzyme
MeSH terms
Cyclic AMP, Adrenal Cortex, Adult, Aged, Cells, Cultured, Cholesterol Side-Chain Cleavage Enzyme, Dehydroepiandrosterone, Female, Humans, Hydrocortisone, Insulin, Male, Middle Aged, RNA, Messenger, Steroid 21-Hydroxylase, 3-Hydroxysteroid Dehydrogenases, Blotting, Northern, Zona Reticularis, Dehydroepiandrosterone Sulfate

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