In the zone: understanding zona reticularis function and its transformation by adrenarche
Open accessAbstract
The human adrenal cortex comprises three distinct zones with unique steroid products, namely the zona glomerulosa, which secretes the mineralocorticoids, the zona fasciculate, which secretes the glucocorticoids and the zona reticularis (ZR), which at adrenarche, begins to produce the so-called adrenal androgens. Of all the adrenal zones, we still understand control of ZR emergence the least, and yet the consequences of such dysregulation can be devastating. Premature adrenarche is a growing problem and the correspondingly inappropriate emergence of ZR function can negatively influence puberty and lead to adult infertility. Our understanding is limited and more needs to be done. The purpose of these three reviews is to provide a survey of where we are in our current understanding of what adrenarche is, and indeed if it is unique to humans at all. Furthermore, these reviews describe what is also known of how the functional ZR emerges during adrenarche and what steroids of physiologic relevance result beyond the widely known DHEA and DHEAS elevated at this time. Such advances in human, primate and indeed stem-cell biology are clearly laying the foundation for new directions in the hunt for the factors involved in the regulation and functional emergence of a ZR at the appropriate time, as well as insight into how they may fail. Given support for these new directions, considerable progress can clearly be made.
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Adrenarche is due to the development of the zona reticularis, which is characterised by an increase in the expression of CYB5A and SULT2A1, and a decrease in the expression of HSD3B2, which in combination favours the biosynthesis of DHEA and DHEAS.
“Adrenarche is due to the development of the zona reticularis which is characterised by an increase in the expression of CYB5A (encoding cytochrome b5) and SULT2A1, and a decrease in the expression of HSD3B2, which in combination favours the biosynthesis of DHEA and DHEAS (Bird, 2012, Gell et al., 1996, Nakamura et al., 2009a).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Bird, 2012
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Cites
Conley, A. J., & Bird, I. M. (1997) · Biology of Reproduction · doi:10.1095/biolreprod56.4.789 · Cited by 295 · see citing works
Self-citationMorley, S. D., Viard, I., Chung, B., Ikeda, Y., Parker, K. L., & Mullins, J. J. (1996) · Molecular Endocrinology · doi:10.1210/mend.10.5.8732689 · Cited by 108 · see citing works
The steroid metabolome of adrenarche
Rege, J., & Rainey, W. E. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0183 · Cited by 97 · see citing works
Adrenarche in nonhuman primates: the evidence for it and the need to redefine it
Conley, A. J., Bernstein, R. M., & Nguyen, A. D. (2012) · Journal of Endocrinology · doi:10.1530/joe-11-0467 · Cited by 53 · see citing works
Zonal Expression of Endothelial Nitric Oxide Synthase in Sheep and Rhesus Adrenal Cortex
Peterson, J. K., Moran, F., Conley, A. J., & Bird, I. M. (2001) · Endocrinology · doi:10.1210/endo.142.12.8537 · Cited by 43 · see citing works
Self-citationPattison, J. C., Abbott, D. H., Wendy Saltzman, A., Conley, A. J., & Bird, I. M. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0554 · Cited by 30 · see citing works
Self-citationBird, I. M., Mason, J. I., & Rainey, W. E. (1998) · Endocrine Research · doi:10.3109/07435809809032614 · Cited by 27 · see citing works
Self-citationAdrenarche: a cell biological perspective
Hornsby, P. J. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0022 · Cited by 21 · see citing works
Expression of AT1‐R in Marmoset Whole Adrenal Glands and Adrenocortical Cells in Culture
Bird, I. M., & Pattison, J. C. (2004) · Endocrine Research · doi:10.1081/erc-200044025 · Cited by 4 · see citing works
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Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217 · see citing works
“Adrenarche is due to the development of the zona reticulariswhich is characterised by an increase in the expression of CYB5A (encoding cytochrome b5) and SULT2A1, and a decrease in the expression of HSD3B2, which in combination favours the biosynthesis of DHEA and DHEAS (Bird, 2012; Gell et al., 1996; Nakamura et al.,…”
- Authors
- Bird, I. M.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Bird, Ian M
- ORCID
- Bird, Ian M
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2012-06-14
- Volume
- 214
- Issue
- 2
- Pages
- 109-111
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2159259175
- Cited by
- 23
- References
- 9
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- zona reticularis, adrenarche, adrenal androgens, dehydroepiandrosterone, dehydroepiandrosterone sulfate, premature adrenarche, puberty, adrenal cortex, zona fasciculata, zona glomerulosa, stem cell biology
- MeSH terms
- Adolescent, Adrenal Cortex, Adrenal Glands, Adult, Animals, Child, Child Development, Humans, Models, Biological, Zona Reticularis, Comprehension, Adrenarche, Mice, Rats
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