Editing Adrenal cortex (section)

== Layers ==
<!-- This section is linked from [[Reticular layer]] -->

The adrenal cortex comprises three main zones, or layers that are regulated by distinct hormones as noted below.  This ''anatomic zonation'' can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics.<ref name="whitehead">{{cite book |author1=Whitehead, Saffron A. |author2=Nussey, Stephen |title=Endocrinology: an integrated approach |publisher=BIOS |location=Oxford |year=2001 |pages=122 |isbn=978-1-85996-252-7 }}</ref>

=== Zona glomerulosa ===
The outermost layer, the [[zona glomerulosa]] is the main site for the production of [[aldosterone]], a [[mineralocorticoid]]. The synthesis and secretion of aldosterone are mainly regulated by the [[renin–angiotensin–aldosterone system]]. The zona glomerulosa cells express a specific enzyme [[aldosterone synthase]] (also known as [[Aldosterone synthase|CYP11B2]]).<ref name="pmid1775135">{{cite journal |vauthors=Curnow KM, Tusie-Luna MT, Pascoe L|display-authors=etal |title=The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex |journal=Mol. Endocrinol. |volume=5 |issue=10 |pages=1513–22 |date=October 1991 |pmid=1775135 |doi=10.1210/mend-5-10-1513|doi-access=free }}</ref><ref name="pmid8333830">{{cite journal |vauthors=Zhou M, Gomez-Sanchez CE |title=Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant |journal=Biochem. Biophys. Res. Commun. |volume=194 |issue=1 |pages=112–7 |date=July 1993 |pmid=8333830 |doi=10.1006/bbrc.1993.1792}}</ref> Aldosterone is largely responsible for the long-term [[regulation of blood pressure]].<ref name=Marieb>Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14</ref> [[Aldosterone]]'s effects are on the [[distal convoluted tubule]] and [[Collecting duct system|collecting duct of the kidney]] where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct).<ref name="Marieb"/> Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent [[calcium]] entry through low-voltage activated [[Calcium channel|Ca<sup>2+</sup> channels]], isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit [[Calcium|Ca<sup>2+</sup>]] channels entry.<ref name="pmid22546854">{{cite journal |vauthors=Hu C, Rusin CG, Tan Z, Guagliardo NA, Barrett PQ |title=Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators |journal=J. Clin. Invest. |volume=122 |issue=6 |pages=2046–53 |date=June 2012 |pmid=22546854 |doi=10.1172/JCI61996 |pmc=3966877}}</ref>

The secretion of aldosterone is also stimulated by [[adrenocorticotropic hormone]] (ACTH).<ref name="1995-Hanukoglu-A">{{cite journal | vauthors = Hanukoglu A, Fried D, Nakash I, Hanukoglu I | title = Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants. | journal = Eur J Endocrinol | volume = 133 | issue = 5 | pages = 552–6 |date=Nov 1995 | doi = 10.1530/eje.0.1330552 | pmid = 7581984 | s2cid = 44439040 }}</ref>

The cells of the zona glomerulosa do not express [[Steroid 11β-hydroxylase|11β-hydroxylase]] and [[17α-hydroxylase]]. This is the reason zona glomerulosa cannot synthesize [[cortisol]], [[corticosterone]], or sex hormones ([[Androgen|androgens]]).<ref name=":0">{{Cite book |last=Barrett |first=Kim E. |url=https://www.worldcat.org/oclc/1076268769 |title=Ganong's review of medical physiology |date=2019 |others=Susan M. Barman, Heddwen L. Brooks, Jason X.-J. Yuan, William F. Preceded by: Ganong |isbn=9781260122404 |edition=26th |location=[New York] |pages=337 |oclc=1076268769}}</ref>
The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors<ref name="pmid9694576">{{cite journal |vauthors=Ehrhart-Bornstein M, Hilbers U |title=Neuroendocrine properties of adrenocortical cells |journal=Horm. Metab. Res. |volume=30 |issue=6–7 |pages=436–9 |year=1998 |pmid=9694576 |doi=10.1055/s-2007-978911|s2cid=260169208 |url=https://zenodo.org/record/1236012 }}</ref><ref name="pmid11889190">{{cite journal |vauthors=Lefebvre H, Cartier D, Duparc C|display-authors=etal |title=Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=3 |pages=1211–6 |date=March 2002 |pmid=11889190 |doi=10.1210/jcem.87.3.8327|doi-access= }}</ref><ref name="pmid17911395">{{cite journal |vauthors=Ye P, Mariniello B, Mantero F, Shibata H, Rainey WE |title=G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism |journal=J. Endocrinol. |volume=195 |issue=1 |pages=39–48 |date=October 2007 |pmid=17911395 |doi=10.1677/JOE-07-0037|doi-access=free }}</ref> and it was suggested that the expression of proteins like the [[neuronal cell adhesion molecule]] (NCAM) in the cells of the zona glomerulosa reflects the regenerative feature of these cells, which would lose NCAM immunoreactivity after moving to the [[zona fasciculata]].<ref name="pmid9694576" /><ref name="pmid9449652">{{cite journal |vauthors=Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lübke C, Ehrhart-Bornstein M |title=Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells |journal=Endocrinology |volume=139 |issue=2 |pages=772–80 |date=February 1998 |pmid=9449652 |doi=10.1210/endo.139.2.5740|doi-access=free }}</ref> However, together with other data on [[neuroendocrine]] properties of zona glomerulosa cells, NCAM expression may reflect a neuroendocrine differentiation of these cells.<ref name="pmid9694576" />

=== Zona fasciculata ===
Situated between the glomerulosa and reticularis, the cells of the [[zona fasciculata]] synthesize and secrete [[glucocorticoid]]s (such as [[11-deoxycorticosterone]], [[corticosterone]], and [[cortisol]]), as well as small amounts of adrenal [[androgen]]s and [[estrogen]]s.<ref name=":1">{{Cite book |last=Hall |first=John E. |url=https://www.worldcat.org/oclc/1129099861 |title=Guyton and Hall textbook of medical physiology |date=2021 |others=Michael E. Hall |isbn=978-0-323-59712-8 |edition=14th |location=Philadelphia, PA |pages=956 |oclc=1129099861}}</ref> The zona fasciculata has more [[3β-Hydroxysteroid dehydrogenase|3β-hydroxysteroid dehydrogenase]] activity than the zona reticularis. Therefore, the zona fasciculata makes more [[11-deoxycorticosterone]], [[corticosterone]], and [[cortisol]].<ref name=":0" /> The major hormone that stimulates cortisol secretion in humans is the ACTH that is released from the [[anterior pituitary]].<ref name="1995-Hanukoglu-A" /> It has been shown that the steroidogenic capacity of the zona fasciculata increases during illness in infants.<ref name="1995-Hanukoglu-A" />

=== Zona reticularis ===
The innermost cortical layer, the [[zona reticularis]], produces adrenal androgens, as well as small amounts of estrogens and some glucocorticoids.<ref name=":1" /> The zona reticularis has more of the cofactors required for the [[17,20 lyase|17,20-lyase]] activity of [[17α-hydroxylase]] than zona fasciculata. Therefore, the zona reticularis makes more [[androgen]]s,<ref name=":0" /> mainly [[dehydroepiandrosterone]] (DHEA), [[DHEA sulfate]] (DHEA-S), and [[androstenedione]] (the precursor to [[testosterone]]) in humans. The secretion of DHEAS is also stimulated by ACTH.<ref name="1995-Hanukoglu-A" />