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

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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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Authors: Endoh, A., Kristiansen, S. B., Casson, P. R., Buster, J. E., & Hornsby, P. J.
Affiliations: Baylor College of Medicine (US)
ORCID: Endoh, A
Kristiansen, S B
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 › Endocrinology › 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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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.

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