Adrenal gland

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Adrenal Gland
Illu endocrine system New.png
Illu adrenal gland.jpg
Adrenal gland
Details
LatinGlandula suprarenalis
PrecursorMesoderm and neural crest
SystemEndocrine system
Superior, middle and inferior suprarenal arteries
Suprarenal veins
Celiac and renal plexus
Lumbar lymph nodes
Identifiers
Gray'sp.1278
MeSHA06.407.071
Dorlands
/Elsevier
Adrenal gland
TAA11.5.00.001
FMA9604
Anatomical terminology
 
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Adrenal Gland
Illu endocrine system New.png
Illu adrenal gland.jpg
Adrenal gland
Details
LatinGlandula suprarenalis
PrecursorMesoderm and neural crest
SystemEndocrine system
Superior, middle and inferior suprarenal arteries
Suprarenal veins
Celiac and renal plexus
Lumbar lymph nodes
Identifiers
Gray'sp.1278
MeSHA06.407.071
Dorlands
/Elsevier
Adrenal gland
TAA11.5.00.001
FMA9604
Anatomical terminology

In mammals, the adrenal glands (also known as suprarenal glands) are endocrine glands that are located on the top of the kidneys. They are chiefly responsible for releasing hormones in response to stress through the synthesis of corticosteroids such as cortisol and catecholamines such as epinephrine (adrenaline) and norepinephrine (noradrenaline). They also produce androgens in their innermost cortical layer. The adrenal glands affect kidney function through the secretion of aldosterone, and recent data (1998) suggest that adrenocortical cells under pathological as well as under physiological conditions show neuroendocrine properties; within normal adrenal glands, this neuroendocrine differentiation seems to be restricted to cells of the zona glomerulosa and might be important for an autocrine regulation of adrenocortical function.[1]

Structure[edit]

The adrenal glands are located bilaterally in the retroperitoneum superior and slightly medial to the kidneys. In humans, the right adrenal gland is pyramidal in shape, whereas the left adrenal gland is semilunar in shape;[2] in non-humans, they are quadrilateral in shape. The combined weight of the adrenal glands in an adult human ranges from 7 to 10 grams.[3]

Histology section of human adrenal gland, showing the different layers that compose it. From the surface to the center: zona glomerulosa, zona fasciculata, zona reticularis, medulla. In the medulla, the central adrenomedullary vein is visible.

The adrenal glands are surrounded by an adipose capsule and are enclosed within the renal fascia, a fibrous structure that also surrounds the kidney. A weak septum of connective tissue separates the glands from the kidneys and facillitates surgical removal of the kidneys without damage to the glands. The adrenal glands are in close relationship with the diaphragm, and are attached to the crura of the diaphragm by means of the renal fascia.[4]

Each adrenal gland has two anatomically and functionally distinct parts, the outer adrenal cortex and the inner medulla, both of which produce hormones. The cortex mainly produces aldosterone, cortisol and androgens, while the medulla produces adrenaline and noradrenaline.

Cortex[edit]

Main article: Adrenal cortex

The adrenal cortex is devoted to production of corticosteroid and androgen hormones. Specific cortical cells produce particular hormones including aldosterone, cortisol, and androgens such as androstenedione. Under normal unstressed conditions, the human adrenal glands produce the equivalent of 35–40 mg of cortisone acetate per day.[5]

The adrenal cortex comprises three zones, or layers. 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.[6] The adrenal cortex exhibits functional zonation as well: by virtue of the characteristic enzymes present in each zone, the zones produce and secrete distinct hormones.[6]

Zona glomerulosa[edit]

Sections of human adrenal glands immunostained for neuronal cell adhesion molecule (NCAM). Staining for NCAM was restricted to the zona glomerulosa (zg) and the adrenal medulla (m).[1]

The outermost layer of the adrenal cortex, the zona glomerulosa, lies immediatly under the fibrous capsule of the gland. Cells in this layer form ovoid groups, separated by trabeculae of connective tissue that are continuous with the fibrous capsule of the gland and carry wide capillaries.[7] This layer is the main site for production of aldosterone, a mineralocorticoid, by the action of the enzyme aldosterone synthase.[8][9] Aldosterone is a hormone largely responsible for the long-term regulation of blood pressure.[10]

The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors[1][11][12] 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.[1][13] However, together with other data on neuroendocrine properties of zona glomerulosa cells, NCAM expression may reflect a neuroendocrine differentiation of these cells.[1] Voltage-dependent calcium channels have been detected in the zona glomerulosa of the human adrenal, which suggests that calcium-channel blockers may directly influence the adrenocortical biosynthesis of aldosterone in vivo.[14]

Zona fasciculata[edit]

Situated between the glomerulosa and reticularis, the zona fasciculata is responsible for producing mainly glucocorticoids such as cortisol.[15] It is the widest of the three layers as it composes nearly 80% of the cortical volume.[16] The cells, arranged in columns radially oriented towards the medulla, have numerous lipid droplets responsible of the pale staining nature of the cytoplasm. Abundant mitochondria and a complex smooth endoplasmic reticulum are also present in the cells of this layer.[7]

Zona reticularis[edit]

The innermost cortical layer, the zona reticularis, lies directly next to the medulla. It produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.[15] Its small cells form irregular cords and clusters, separated by capillaries and connective tissue. The cells contain relatively small quantities of cytoplasm and lipid droplets, and sometimes display brown lipofuscin pigment.[7]

Medulla[edit]

Main article: Adrenal medulla

The adrenal medulla is the core of the adrenal gland, and is surrounded by the adrenal cortex. It secretes approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine).[15] The chromaffin cells of the medulla, named for their characteristic brown staining with chromic acid salts, are the body's main source of the circulating catecholamines adrenaline and noradrenaline. Catecholamines are derived from the amino acid tyrosine and these water-soluble hormones are the major hormones underlying the fight-or-flight response.

To carry out its part of this response, the adrenal medulla receives input from the sympathetic nervous system through preganglionic fibers originating in the thoracic spinal cord from T5–T11.[17] Because it is innervated by preganglionic nerve fibers, the adrenal medulla can be considered as a specialized sympathetic ganglion.[17] Unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct synapses and releases its secretions directly into the blood.

Cortisol also promotes adrenaline synthesis in the medulla. Produced in the cortex, cortisol reaches the adrenal medulla and at high levels, the hormone can promote the upregulation of phenylethanolamine N-methyltransferase (PNMT), thereby increasing adrenaline synthesis and secretion.[6]

Blood supply[edit]

Although variations of the blood supply to the adrenal glands (and indeed the kidneys themselves) are common, there are usually three arteries that supply each adrenal gland:

Venous drainage of the adrenal glands is achieved via the suprarenal veins:

In the medulla a particular type of blood vessel called central adrenomedullary vein exists. Its structure is different from the other veins in that the smooth muscle in its tunica media (the middle layer of the vessel) is arranged in conspicuous, longitudinally oriented bundles.[16]

The suprarenal vein exits the adrenal gland through a depression on its anterior surface known as the hilum. Note that the arteries supplying the suprarenal gland do not pass through the hilum.[18] The suprarenal veins may form anastomoses with the inferior phrenic veins. Since the right supra-renal vein is short and drains directly into the inferior vena cava it is likely to injure the latter during removal of right adrenal for various reasons.

The adrenal glands (alongside the thyroid gland) have one of the greatest blood supply per gram of tissue of any organ. Up to 60 arterioles may enter each adrenal gland.[19] This may be one of the reasons lung cancer commonly metastasizes to the adrenals.

Function[edit]

The adrenal gland secretes a number of different hormones which are metabolised by enzymes either within the gland or in other parts of the body. These hormones are involved in a number of different pathways.[20]

Corticosteroid production[edit]

All corticosteroid hormones share cholesterol as a common precursor. In consequence, the first step in steroidogenesis is cholesterol uptake or synthesis. Cells that produce steroid hormones provide themselves with cholesterol in various ways. Their main source is dietary cholesterol transported in the blood as LDL, which enters the cells through receptor-mediated endocytosis, altough endogenous synthesis in the endoplasmic reticulum is sufficient when LDL levels are abnormally low as represented in people with abetalipoproteinemia (a genetic disorder of intestinal lipid absorption).[21] In lysosomes, cholesterol is separated from the proteic component of LDL and then stored within cell membranes or bound with proteins.[22]

The initial part of conversion of cholesterol into steroid hormones involves a number of enzymes of the cytochrome P450 family that are located in the inner membrane of mitochondria. Transport of cholesterol from the outer to the inner membrane is facilitated by steroidogenic acute regulatory protein (StAR) and is the rate-limiting step of steroid synthesis.[22] The functional zonation of the adrenal cortex is determined by distinct enzymes present in its different layers, explaining how the cortex produces hormones that are unique for a particular layer from a common precursor.[21]

The first enzymatic step in the production of all steroid hormones is cleavage of the cholesterol side chain, a reaction that forms pregnenolone as a product and is catalyzed by the enzyme P450scc. After the production of pregnenolone, specific enzymes of each cortical layer further modify it. Enzymes involved in this process include both mitochondrial and cytoplasmic P450s and hydroxysteroid dehydrogenases (HSDs). Usually a number of intermediate steps in which pregnenolone is modified several times are required to form the functional hormones.[23] Enzymes that catalyze reactions in these metabolic pathways are involved in a number of endocrine diseases. For example, the most common form of congenital adrenal hyperplasia develops as a result of deficiency of 21-hydroxylase, an enzyme involved in an intermediate step of cortisol production.[24]

Catecholamine production[edit]

Epinephrine and norepinephrine are catecholamines, water-soluble subtances that have a structure made of a catechol group and an amino group. The adrenal glands are responsible for the majority of circulating epinephrine (adrenaline) in the body, but only for a small amount of circulating norepinephrine (noradrenaline).[20] These hormones are released in the adrenal medulla, which is richly vascular. Epinephrine and norepinephrine act at adrenoreceptors throughout the body, with effects that include increase of blood pressure and heart rate.[20]

Catecholamines are produced in chromaffin cells (the main type of cells in the adrenal medulla) from tyrosine, a non-essential amino acid derived from food or produced from phenylalanine in the liver. The enzyme tyrosine hydroxylase converts tyrosine to L-DOPA in the first step of catecholamine synthesis. L-DOPA is then converted to dopamine before it can be turned into norepinephrine. In the cytosol, norepinephrine is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT.[21]

The adrenal medulla is innervated by splanchnic nerves of the sympathetic nervous system, which signal the release of catecholamines from the storage granules by stimulating the opening of calcium channels in the cell membrane.[25]

Effects of adrenal hormones[edit]

Aldosterone and mineralocorticoids[edit]

Main article: Aldosterone

Aldosterone's effects are on the distal convoluted tubule and 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).[10] 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 Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry.[26] However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca2+ channels signal that can be controlled by angiotensin II and extracellular potassium, the 2 major regulators of aldosterone production.[26] Angiotensin II originates from plasmatic angiotensin I after the conversion of angiotensinogen by renin produced by the juxtaglomerular cells of the kidney.[15]

Cortisol and glucocorticoids[edit]

Main article: Cortisol

Cortisol is the main glucocorticoid under normal conditions and its actions include mobilization of fats, proteins, and carbohydrates, but it does not increase under starvation conditions.[15] Additionally, cortisol enhances the activity of other hormones including glucagon and catecholamines. The zona fasciculata secretes a basal level of cortisol but can also produce bursts of the hormone in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.

Adrenal androgens[edit]

Cells in zona reticularis of the adrenal glands produce male sex hormones, or androgens, the most important of which is DHEA. In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such as testosterone and DHT or to estrogens (female sex hormones) in the gonads, acting in this way as a metabolic intermediate.[27]

Epinephrine and norepinephrine[edit]

Main article: Epinephrine

Epinephrine and norepinephrine are catecholamines that act at adrenoreceptors throughout the body, with effects including constriction of small arteries, dilation of veins, and increasing the heart rate.[20]

Development[edit]

The adrenal glands are composed of two very heterogenous types of tissue: in the center there is the adrenal medulla, which produces and releases mostly adrenaline to the blood in stress situations as part of the sympathetic nervous system. Surrounding the medulla is the cortex, which produces a wide variety of steroid hormones. These tissues come from different embryological precursors and have distinct prenatal developments.

Cortex[edit]

Adrenal cortex tissue is derived from the intermediate mesoderm. It first appears 33 days after fertilisation, shows steroidogenic (steroid hormone production) capabilities by the eighth week and undergoes rapid growth during the first trimester of pregnancy. The fetal adrenal cortex is different from its adult counterpart, as it is composed of two distinct zones: the inner fetal zone, which carries most of the hormone-producing activity, and the outer definitive zone, which is in a proliferative phase. The fetal zone produces large amounts of adrenal androgens (male sex hormones) that are used by the placenta for estrogen biosynthesis.[28] Cortical development of the adrenal gland is regulated mostly by ACTH, a hormone produced by the pituitary gland that stimulates cortisol synthesis.[29] During midgestation, the fetal zone occupies most of the cortical volume and produces 100–200 mg/day of DHEA-S, an androgen and precursor of both androgens and estrogens (female sex hormones).[30] Adrenal hormones, especially glucocorticoids such as cortisol are considered essential for prenatal development of organs, particularly for the maduration of the fetal lungs. The adrenal gland decreases in size after birth because of the rapid disappearance of the fetal zone, with a decrease in androgen secretion.[28]

Adrenarche[edit]

Main article: Adrenarche

During childhood, androgen synthesis and secretion remain low, but several years before puberty (from 6–8 years of age) changes occur in both anatomical and functional aspects of cortical androgen production that lead to increased secretion of DHEA and DHEA-S. These changes are part of a process called adrenarche, which has only been described in humans and some other primates. Adrenarche is independent of ACTH or gonadotropins and correlates with a progressive thickening of the zona reticularis layer of the cortex. Functionally, adrenarche provides a source of androgens for the development of axillary and pubic hair before the beginning of puberty.[31][32]

Medulla[edit]

The adrenal medulla is derived from a type of cells known as neural crest cells, which come from the ectoderm layer of the embryo. These cells migrate from their initial position and aggregate in the vicinity of the dorsal aorta, a primitive blood vessel, which activates the differentiation of these cells through the release of proteins known as BMPs. These cells then undergo a second migration step away from the dorsal aorta to form the the adrenal medulla, along other organs of the sympathetic nervous system.[33] Cells of the adrenal medulla are also called chromaffin cells because they contain granules that stain with chromium salts, a characteristic not present in all sympathetic organs. Glucocorticoid production by the adrenal cortex was thought to be responsible for this differentiation, but now the available data suggest that BMP-4 secreted in the adrenal tissue is the primary responsible for the differentiation, and that glucocorticoids have a role in the posterior development of the cells.[34]

Clinical significance[edit]

History[edit]

Etymology[edit]

The adrenal glands are named for their location relative to the kidneys. The term "adrenal" comes from ad- (Latin, "near") and renes (Latin, "kidney").[35] Similarly, "suprarenal" is derived from supra- (Latin, "above") and renes.

See also[edit]

This article uses anatomical terminology; for an overview, see anatomical terminology.

References[edit]

  1. ^ a b c d e Ehrhart-Bornstein M, Hilbers U (June–July 1998). "Neuroendocrine properties of adrenocortical cells.". Horm Metab Res. 30 (6-7): 436–439. doi:10.1055/s-2007-978911. PMID 9694576. 
  2. ^ "FeedBack What Is Adrenal Gland? Adrenal Gland Diseases". OrgansOfTheBody. Retrieved 2013-09-17. 
  3. ^ Page 18 in: Boué A, Nicolas A, Montagnon B (June 1971). "Reinfection with rubella in pregnant women". Lancet 297 (7712): 1251–3. doi:10.1016/S0140-6736(71)91775-2. PMID 4104713. 
  4. ^ Moore KL, Dalley AF, Agur AM (2013). Clinically Oriented Anatomy, 7th ed. Lippincott Williams & Wilkins. p. 294, 298. ISBN 978-1-4511-8447-1. 
  5. ^ Jefferies, William McK (2004). Safe uses of cortisol. Springfield, Ill: Charles C. Thomas. ISBN 0-398-07500-X. 
  6. ^ a b c Whitehead, Saffron A.; Nussey, Stephen (2001). Endocrinology: an integrated approach. Oxford: BIOS. p. 122. ISBN 1-85996-252-1. 
  7. ^ a b c Young B, Woodford P, O'Dowd G (2013). Wheater's Functional Histology: A Text and Colour Atlas (6th ed.). Elsevier. p. 329. ISBN 978-0702047473. 
  8. ^ Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL, White PC (October 1991). "The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex.". Mol. Endocrinol. 5 (10): 1513–1522. doi:10.1210/mend-5-10-1513. PMID 1775135. 
  9. ^ Zhou M, Gomez-Sanchez CE (July 1993). "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant.". Biochem Biophys Res Commun. 194 (1): 112–117. doi:10.1006/bbrc.1993.1792. PMID 8333830. 
  10. ^ a b Marieb, EN; Hoehn, K (2012). Human anatomy & physiology (9th ed.). Pearson. p. 629. ISBN 978-0321743268. 
  11. ^ Lefebvre H, Cartier D, Duparc C, Lihrmann I, Contesse V, Delarue C, Godin M, Fischmeister R, Vaudry H, Kuhn JM (2002). "Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies.". J Clin Endocrinol Metab. 87 (3): 1211–1216. doi:10.1210/jc.87.3.1211. PMID 11889190. 
  12. ^ Ye P, Mariniello B, Mantero F, Shibata H, Rainey WE (2007). "G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism.". J Endocrinol. 195 (1): 39–48. doi:10.1677/JOE-07-0037. PMID 17911395. 
  13. ^ Haidan A, Bornstein SR, Glasow A, Uhlmann K, Lübke C, Ehrhart-Bornstein M (February 1998). "Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells.". Endocrinology. 139 (2): 772–780. doi:10.1210/en.139.2.772. PMID 9449652. 
  14. ^ Saulo J.A. Felizola, Takashi Maekawa, Yasuhiro Nakamura, Fumitoshi Satoh, Yoshikiyo Ono, Kumi Kikuchi, Shizuka Aritomi, Keiichi Ikeda, Michihiro Yoshimura, Katsuyoshi Tojo, Hironobu Sasano. (2014). "Voltage-gated calcium channels in the human adrenal and primary aldosteronism.". J Steroid Biochem Mol Biol. 144 (part B): 410–416. doi:10.1016/j.jsbmb.2014.08.012. PMID 25151951. 
  15. ^ a b c d e Dunn R. B.; Kudrath W.; Passo S.S.; Wilson L.B. (2011). "10". Kaplan USMLE Step 1 Physiology Lecture Notes. pp. 263–289. 
  16. ^ a b Ross M, Pawlina W (2011). Histology: A Text and Atlas (6th ed.). Lippincott Williams & Wilkins. p. 780. ISBN 978-0-7817-7200-6. 
  17. ^ a b Sapru, Hreday N.; Siegel, Allan (2007). Essential Neuroscience. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN 0-7817-9121-9. 
  18. ^ http://medicine.academic.ru/130143/hilum_glandulae_suprarenalis
  19. ^ Mirilas P, Skandalakis JE, Colborn GL, Weidman TA, Foster RS, Kingsnorth A, Skandalakis LJ, Skandalakis PN (2004). Surgical Anatomy: The Embryologic And Anatomic Basis Of Modern Surgery. McGraw-Hill Professional Publishing. ISBN 960-399-074-4. 
  20. ^ a b c d Britton, the editors Nicki R. Colledge, Brian R. Walker, Stuart H. Ralston ; illustrated by Robert (2010). Davidson's principles and practice of medicine. (21st ed. ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 768–778. ISBN 978-0-7020-3085-7. 
  21. ^ a b c Melmed, S; Polonsky, KS; Larsen, PR; Kronenberg, HM (2011). Williams Textbook of Endocrinology (12th ed.). Saunders. ISBN 978-1437703245. 
  22. ^ a b Miller, WL; Bose, HS (2011). "Early steps in steroidogenesis: intracellular cholesterol trafficking". Journal of Lipid Research 52 (12): 2111–2135. doi:10.1194/jlr.R016675. PMC 3283258. PMID 21976778. 
  23. ^ Miller, WL; Auchus, RJ (2011). "The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.". Endocrine Reviews 32 (1): 81–151. doi:10.1210/er.2010-0013. PMC 3365799. PMID 21051590. 
  24. ^ Charmandari, E; Brook, CG; Hindmarsh, PC (2004). "Classic congenital adrenal hyperplasia and puberty.". European Journal of Endocrinology 151 (Suppl 3): 77–82. doi:10.1530/eje.0.151U077. PMID 15554890. 
  25. ^ García, AG; García de Diego, AM; Gandía, L; Borges, R; García Sancho, J (2006). "Calcium signaling and exocytosis in adrenal chromaffin cells.". Physiological Reviews 86 (4): 1093–1131. doi:10.1152/physrev.00039.2005. PMID 17015485. 
  26. ^ a b Hu C, Rusin CG, Tan Z, Guagliardo NA, Barrett PQ (June 2012). "Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electricaloscillators.". J Clin Invest. 122 (6): 2046–2053. doi:10.1172/JCI61996. PMID 22546854. 
  27. ^ Hall JE, Guyton AC (2010). Guyton and Hall Textbook of Medical Physiology, 12th edition. Saunders. ISBN 978-1416045748. 
  28. ^ a b Ishimoto H, Jaffe RB (2011). "Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit". Endocrine Reviews 32 (3): 317–355. doi:10.1210/er.2010-0001. PMC 3365797. PMID 21051591. 
  29. ^ Hoeflich A, Bielohuby M. (2009). "Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2". Journal of Molecular Endocrinology 42 (3): 191–203. doi:10.1210/edrv.18.3.0304. PMID 19052254. 
  30. ^ Mesiano S, Jaffe RB (1997). "Developmental and Functional Biology of the Primate Fetal Adrenal Cortex". Endocrine Reviews 18 (3): 378–403. doi:10.1210/edrv.18.3.0304. PMID 9183569. 
  31. ^ Hornsby, PJ (2012). "Adrenarche: a cell biological perspective.". The Journal of Endocrinology 214 (2): 113–119. doi:10.1530/JOE-12-0022. PMID 22573830. 
  32. ^ Rege, J; Rainey, WE (2012). "The steroid metabolome of adrenarche.". The Journal of Endocrinology 214 (2): 133–143. doi:10.1530/JOE-12-0183. PMC 4041616. PMID 22715193. 
  33. ^ Huber K (2006). "The sympathoadrenal cell lineage: Specification, diversification, and new perspectives". Developmental Biology 298 (2): 335–343. doi:10.1016/j.ydbio.2006.07.010. PMID 16928368. 
  34. ^ Unsicker K, Huber K, Schober A, Kalcheim C (2013). "Resolved and open issues in chromaffin cell development". Mechanisms of Development 130 (6–8): 324–329. doi:10.1016/j.mod.2012.11.004. PMID 23220335. 
  35. ^ "What Are The Adrenal Glands?". About.com. Retrieved 2013-09-18. 

External links[edit]