The 2 adrenal glands (= suprarenal gland, glandulæ suprarenales) are named by their anatomical postion sitting above the 2 kidneys (renal). The 2 main parts of the adrenals have different embryonic origins. The inside core adrenal medulla is neural crest in origin. The outside adrenal cortex is derived from mesothelium and can be further divided into 3 distinct layers (zona reticularis, zona fasiculata, zona glomerulosa) each with distinct hormonal functions.
During fetal development, adrenal hormones are involved with the maturation of the lung and other developing systems.
Adrenal Gland cartoon (More? Large Adrenal Gland cartoon | Neural Crest Notes)
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Human fetus (10 week, 40mm, parasagittal section) shows location of the developing adrenal gland. (More? Adrenal Cortex) |
In the embryo, neural crest cells migrate to a location above the developing metanephros. (More? Adrenal Medulla) |
Mesenchyme surrounding these cells differentiates to form a fetal cortex. This fetal cortex is later replaced by the adult cortex.
Page Links: Introduction | Some Recent Findings | Reading | Development Overview | Adrenal Medulla | Adrenal Cortex | Abnormalities | Congenital Adrenal Hyperplasia | Serial Images | WWW Links | References | Glossary
Huber K. The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol. 2006 Oct 15;298(2):335-43. Epub 2006 Jul 14.
"Sympathoadrenal (SA) cells constitute a major lineage among NC derivatives; they give rise to sympathetic neurons, neuroendocrine chromaffin cells, and the intermediate small intensely fluorescent (SIF) cells."
Hanley NA, Arlt W. The human fetal adrenal cortex and the window of sexual differentiation. Trends Endocrinol Metab. 2006 Dec;17(10):391-7.
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Historic Images: |
Kidney and adrenal |
Adrenal medulla and cortex |
Human embryo (stage 22) adrenal gland showing the fetal and permanent adrenal cortex. Note that the medulla of the adrenal gland is not yet encapsulated by the cortex. |
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Medulla - Neural crest cells migrate toward the coelomic cavity wall and form the adrenal medulla. These chromaffin (chromaphil) cells originally named because of their staining (yellow) with chromium salts. (More? Adrenal Medulla)
Cortex - Week 4 celomic epithelium (mesothelium) cells proliferate initially forming small buds that separate from the epithelium. Week 6 these now mesenchymal cells first form the fetal adrenal cortex which will be later replaced by the adult cortex. (More? Adrenal Cortex)
Neural crest cells migrate toward the coelomic cavity wall and form the adrenal medulla. These chromaffin (chromaphil) cells originally named because of their staining (yellow) with chromium salts. (More? Neural Crest Notes)
Cells have a neuron-like morphology and eventually form 2 different cell types on the basis of their endocrine secretion: 80% secrete epinepherine (adrenaline), 20% secrete norepinepherine (noradrenaline).
Adult Medulla Function
Hormone secretion often described as “Fight-flight response", having different effects on different systems.
Sympathetic stimulation can increase hormone release.
Hormone targets most cells with receptors (alpha 1 and beta 1): increases cardiac activity, blood pressure, glycogen breakdown, blood glucose, adipose lipid release.
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Human embryo (7 weeks, stage 22) adrenal gland showing the fetal and permanent adrenal cortex. Note that the medulla of the adrenal gland is not yet encapsulated by the cortex. |
Human fetus (10 week, 40mm, parasagittal section) shows location of the developing adrenal gland. The spongy appearance at the centre of the adrenal is the degenerating fetal cortex. The dense region around the outside of the adrenal is the developing adult cortex. (More? Human Fetus (10 week)) |
Week 4 - celomic epithelium (mesothelium) cells proliferate initially forming small buds that separate from the epithelium.
Week 6 - these now mesenchymal cells surrounding the developing medulla cells differentiate first form the fetal adrenal cortex which will be later replaced by the adult cortex.
Week 8 to 9 - fetal adrenal cortex synthesizes cortisol and is maximal at 8-9 weeks post conception (wpc) under the regulation of ACTH (also stimulates androstenedione and testosterone secretion). (More? Goto etal., 2006)
Adult cortex - mesothelium mesenchyme encloses fetal cortex.
Late Fetal Period - differentiates to form cortical zones.
Birth - zona glomerulosa, zona fasiculata present.
Year 3 - zona reticularis present.
Fetal Cortex
Fetal adrenal cortical growth involves several cellular processes: hypertrophy, hyperplasia, apoptosis, and migration.
In the second and third trimesters a steroid precursor (DEA) and sulphated derivative (DHEAS) which is converted by placenta into estrogen.
Three functional zones:
Adult Cortex
Reticularis - narrow band, many small cells and capillaries androgens.
Fasiculata - high lipid content, pale foamy cells cortisol, corticosterone, cortisone.
Glomerulosa - small cells, cords or oval groups, aldosterone.
Stage 13/14 Embryo - no adrenal development visible at this stage | Stage 22 Human Embryo | Stage 22 Human Embryo High Power
Stage 22 Adrenal Gland
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High Power Images Stage 22 Adrenal Gland
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E6: Overview of embryo (stage 22) at the level of the liver where adrenals are seen. |
F3: Fetal and permanent adrenal cortex. The medulla of the adrenal gland is of neural crest origin and it is not yet encapsulated by the cortex. |
Congenital Adrenal Hyperplasia | Pheochromocytomas |
Congenital Adrenal Hyperplasia (CAH)
A family of inherited disorders of adrenal steroidogenesis enzymes which impairs cortisol production by the adrenal cortex.
Enzymes most commonly affected: 21-hydroxylase (21-OH), 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase.
Enzymes less commonly affected: 17alpha-hydroxylase/17,20-lyase and cholesterol desmolase.
Classical CAH - androgen excess leads newborn females with external genital ambiguity and postnatal progressive virilization in both sexes. (More? Genital Notes | Genital Abnormalities)
Pheochromocytomas (PCC)
Catecholamine-producing (neuro)endocrine tumor located in the adrenal medulla. Similar catecholamine-producing tumors outside the adrenal gland are called paragangliomas (PGL).
Links: Journals | Online Textbooks | Search Textbooks | PubMed | Search PubMed | Glossary
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. 4.7. Embryology of the adrenal gland | The Adrenal Gland | Anatomical and functional zonation in the adrenal cortex
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Figure 13.6. Final differentiation of a trunk neural crest cell committed to become either an adrenomedullary (chromaffin) cell or a sympathetic neuron
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP | Cells Can Respond Abruptly to a Gradually Increasing Concentration of an Extracellular Signal
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct. Adrenal Gland search Results
Search NLM Online Textbooks- "adrenal development" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach
Reviews
Hanley NA, Arlt W. The human fetal adrenal cortex and the window of sexual differentiation. Trends Endocrinol Metab. 2006 Dec;17(10):391-7.
Huber K. The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol. 2006 Oct 15;298(2):335-43.
Yanase T, Gondo S, Okabe T, Tanaka T, Shirohzu H, Fan W, Oba K, Morinaga H, Nomura M, Ohe K, Nawata H. Differentiation and regeneration of adrenal tissues: An initial step toward regeneration therapy for steroid insufficiency. Endocr J. 2006 Aug;53(4):449-59.
Jaffe RB, Mesiano S, Smith R, Coulter CL, Spencer SJ, Chakravorty A. The regulation and role of fetal adrenal development in human pregnancy. Endocr Res. 1998 Aug-Nov;24(3-4):919-26.
Mesiano S, Jaffe RB. Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev. 1997 Jun;18(3):378-403.
(More? Adrenal Review 1999 | Selected Adrenal Papers 1999)
Articles
Villa-Cuesta E, Modolell J. Mutual repression between msh and Iro-C is an essential component of the boundary between body wall and wing in Drosophila. Development. 2005 Aug 10
Goto M, Piper Hanley K, Marcos J, Wood PJ, Wright S, Postle AD, Cameron IT, Mason JI, Wilson DI, Hanley NA. In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J Clin Invest. 2006 Apr;116(4):953-60.
Jaffe RB, Mesiano S, Smith R, Coulter CL, Spencer SJ, Chakravorty A. The regulation and role of fetal adrenal development in human pregnancy. Endocr Res. 1998 Aug-Nov;24(3-4):919-26.
"The rapid growth of the human fetal adrenal gland, which is primarily a reflection of the growth of the unique fetal zone, is regulated by ACTH acting indirectly to stimulate the expression of locally produced growth factors, of which IGF-II and bFGF appear to play key roles. Through most of gestation, the outer definitive zone appears to function as a reservoir of progenitor cells which move centripetally to populate the rest of the gland. At the end of pregnancy, the fetal zone undergoes senescence through an apoptotic process. Activin and TGF-beta are capable of inducing apoptosis in the fetal zone. Corticotropin-releasing hormone, which is produced by the placenta in markedly increased amounts at the end of gestation, may orchestrate a variety of processes, including direct stimulation of fetal adrenal steroidogenesis, culminating in the initiation of parturition."
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Search Mar2007 "adrenal development" 9,393 reference articles of which 2,047 were reviews.
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The developing adrenal gland has both an interesting origin and an intruiging fetal role.
The adrenal gland and placenta also act in synergy, and the notes endocrine placenta should also be read.
Something old, something new....listen to where the term "hormone" came from in the linked podcast.
Please email Dr Mark Hill if you wish to make a comment about this current project.