Endocrine - Adrenal Development

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Adrenal Gland (week 10)

The developing adrenal gland has both an interesting origin and an intriguing fetal role. Furthermore recent studies suggest that the adrenal cortex share a common embryonic origin with the early gonad. The adrenal gland and placenta also act in synergy, and the notes endocrine placenta should also be read.

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. Mesenchyme surrounding these cells differentiates to form a fetal cortex. This fetal cortex is later replaced by the adult cortex. 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 production of precursor for placental estrogen production, ovary and brain development, the maturation of the lung and other developing systems. Dehydroepiandrosterone (DHEA, androstenolone) is produced by the fetal adrenal cortex as dehydroepiandrosterone sulfate (DHEA-S) that the placenta uses to produce estrogens.[1] DHEA, androstenedione, and testosterone can be metabolized to epiandrosterone, and etiocholanolone.

Links: neural crest | Endocrine Lecture | Lecture - Neural Crest Development

Historic Embryology - Adrenal  
1903 Pig Adrenal | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1920 Adrenal | 1930 Human Adrenal | 1940 Adrenal | 1946 Adrenal Cortex | 1957 Human Adrenal

Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | pineal | hypothalamus‎ | pituitary | thyroid | parathyroid | thymus | pancreas | adrenal | endocrine gonad‎ | endocrine placenta | other tissues | Stage 22 | endocrine abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 1903 Pig Adrenal | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Adrenal | 1927 Hypophyseal fossa | 1930 Adrenal | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1935 Pineal | 1937 Pineal | 1935 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal

Some Recent Findings

  • Neuropilins guide preganglionic sympathetic axons and chromaffin cell precursors to establish the adrenal medulla[2] "By combining lineage tracing, gene expression studies, genetic ablation and the analysis of mouse mutants, we demonstrate that preganglionic axons direct chromaffin cell precursors into the adrenal primordia. We further show that preganglionic axons and chromaffin cell precursors require class 3 semaphorin (SEMA3) signalling through neuropilins (NRP) to target the adrenal medulla. Thus, SEMA3 proteins serve as guidance cues to control formation of the adrenal neuroendocrine system by establishing appropriate connections between preganglionic neurons and adrenal chromaffin cells that regulate the autonomic stress response."
  • Human fetal adrenal cells retain age-related stem- and endocrine-differentiation potential in culture[3] "We developed an in vitro human adrenal cell model derived from fetal adrenal specimens at different gestational ages, consisting of neuroendocrine and cortical components and expressing the zona and functional markers of the original fetal organ. These cortical and neuroendocrine progenitor cells retain in vitro an intrinsic gestational-age-related differentiation and functional program. In vitro these cells spontaneously form 3-dimensional structure organoids with a structure similar to the fetal gland. The organoids show morphofunctional features and adrenal steroidogenic factor, steroid acute regulatory, cytochrome-P450-17A1, dosage-sensitive, sex-reversal, adrenal hypoplasia-critical region on chromosome X protein , NOTCH1, and nephroblastoma overexpressed/cysteine-rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene-3; stem (BMI1, nestin); and chromaffin (chromogranin A, tyrosine hydroxylase) markers similar to those of the populations of origin."
  • Adrenal gland size in growth restricted fetuses[4] "To compare the adrenal gland size of fetal growth restricted (FGR) and normal control fetuses. ... The adrenal gland cortex width and the adrenal gland ratio were increased in FGR fetuses compared to normal fetuses." ultrasound
More recent papers  
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Adrenal Development | Adrenal Embryology | Adrenal Medulla Embryology | Fetal Adrenal Cortex Development | Adrenal Cortex Embryology |

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla[5] "We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs). SCPs migrate along the visceral motor nerve to the vicinity of the forming adrenal gland, where they detach from the nerve and form postsynaptic neuroendocrine chromaffin cells."
  • Fetal adrenal gland in the second half of gestation: morphometrical assessment with 3.0T post-mortem MRI[6] "The morphometry of fetal adrenal gland is rarely described with MRI of high magnetic field. The purpose of this study is to assess the normal fetal adrenal gland length (AL), width (AW), height (AH), surface area (AS) and volume (AV) in the second half of gestation with 3.0T post-mortem MRI. Fifty-two fetal specimens of 23-40 weeks gestational age (GA) were scanned by 3.0T MRI. Morphological changes and quantitative measurements of the fetal adrenal gland were analyzed. Asymmetry and sexual dimorphism were also obtained. The shape of the fetal adrenal gland did not change substantially from 23 to 40 weeks GA. The bilateral adrenal glands appeared as a 'Y', pyramidal or half-moon shape after reconstruction. There was a highly linear correlation between AL, AW, AH, AS, AV and GA. AW, AH, AS and AV were larger for the left adrenal gland than the right. No sexual dimorphism was found." magnetic resonance imaging
  • A morphometric study of suprarenal gland development in the fetal period[7] "This study was performed on 172 human fetuses (76 males and 96 females) and 344 fetal suprarenal glands obtained from ages 9-40 weeks of gestation with no external pathology or anomaly. It is found that all parameters increase with gestational age. There was significant correlation between gestational age and all parameters (p < 0.001). No significant differences were observed between sexes for any of the parameters (p > 0.05). There was no difference between the right and left sides of parameters except the thickness of the suprarenal glands. The left suprarenal glands were thicker than the right. The ratio of suprarenal volumes to kidney volumes was determined, and we observed that the ratio decreased during the fetal period."
  • Migration and distribution of neural crest-derived cells in the human adrenal cortex at 9-16 weeks of gestation[8] "In sagittal as well as horizontal sections of human fetuses between 9 and 16 weeks of gestation, we identified chromaffin, ganglion and Schwann-like cells in the developing adrenal gland using immunohistochemistry. Cells showing tyrosine hydroxylase (TH) immunoreactivity (i.e., candidate ganglion cells) entered the fetal cortex mainly from the medial half of the adrenal, but the path of entry also included the ventral, dorsal and caudal aspects. ...The entry of neural crest-derived cells does not appear to be restricted to a hypothetical medial hilus, but occurs widely around the cortex, with or without the accompaniment of Schwann-like cells. These cells advance in lines through the fetal cortex in a cord-like arrangement without destruction of the cortical architecture. Some of the TH-positive cells very likely express chromogranin A before entry into the adrenal."
  • Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence.[9] "Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age."
  • Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit[10] "The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis." (See also Fetal Development)

Adrenal Movies

Adrenal medulla.jpg
 ‎‎Adrenal Medulla
Page | Play
Human fetal adrenal GA32.jpg
 ‎‎Adrenal GA32
Page | Play
Cartoon showing migration of neural crest cells
from original location to form the fetal medulla cells.
Surface rendering of human fetal adrenal glands
in the third trimester (week 30 GA week 32).

Adrenal Overview

  • Richly vascularized - arterioles passing through cortex, capillaries from cortex to medulla, portal-like circulation
  • Fetal Cortex - produces a steroid precursor (DEA), converted by placenta into estrogen
  • Adult Medulla - produces adrenalin (epinephrine), noradrenaline (norepinephrine)
  • Fetal adrenal hormones - influence lung maturation

Cortical Hormones

(steroids) Cortisol, Aldosterone, Dehydroepiandrosterone

  • zona glomerulosa - regulated by renin-angiotensin-aldosterone system controlled by the juxtaglomerular apparatus of the kidney.
  • zona fasciculata - regulated by hypothalamo-pituitary axis with the release of CRH and ACTH respectively.

Medullary Hormones

(amino acid derivatives) Epinephrine, Norepinephrine

Development Overview

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.

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.

Adrenal gland development and steroid hormone synthesis
Fetal adrenal gland steroidogenesis.jpg
Overview cartoon of changes in adrenal gland structure and steroid hormone syntesis[11]
Ontogenesis of steroidogenic enzymes in the human fetal adrenal gland. This schematic representation is divided into portions showing the fetal adrenal gland (right) at the first, second and third trimesters of pregnancy, and the adult adrenal gland (left). During the first trimester, the fetal gland is composed of a definitive zone (DZ, light grey) and a fetal zone (FZ, dark grey).

Fetal zone (FZ) - expressing the P450C17 cytochrome, is responsible for massive secretion of DHEA and DHEA/S, used by the placenta as estrogen precursors.

Second trimester - chromaffin cells (CC, black) originating from the neural crests migrate through the fetal cortex to progressively colonize the center of the gland to form the future medulla (Med).

Third trimester - the newly constituted transitional zone (TZ, medium grey) acquires the enzyme 3ß-HSD while the expression of P450C17 remains, thus allowing the production of fetal cortisol. Near birth, cells of the definitive zone which express only 3ß-HSD, acquire the P450aldo and begin to secrete mineralocorticoids such as aldosterone.

Neonatal - the fetal adrenal regresses strongly (mainly due to the regression of the fetal zone) and recovers progressively during the first years of extra-uterine life.

Adult - adult adrenal gland is composed of the zona glomerulosa (ZGlo, light grey), zona fasciculata (ZFasc , medium grey) and zona reticularis (ZRet, dark grey) responsible for the production of mineralocorticoids (aldosterone), glucocorticoids (cortisol) and androgens (DHEA-DHEA/S), respectively.

{based on data from[12])

  • P450scc - cytochrome P450 side chain cleavage
  • Pregn. - pregnenolone
  • P450C17 - cytochrome P450 17a-hydroxylase, 17-20 lyase
  • 17OHP5 - 17-hydroxy-pregnenolone
  • DHEA/S - dehydroepiandrosterone-sulfate
  • S-Tfase - DHEA sulfotransferase
  • 3ß-HSD - 3ß-hydroxysteroid dehydrogenase
  • Prog. - progesterone
  • 17OHP4 - 17-hydroxyprogesterone
  • P450C21 - cytochrome P450 21-hydroxylase
  • P450C11 - cytochrome P450 11ß-hydroxylase
  • P450aldo - cytochrome P450 aldosterone synthase.
  • Fetal Adrenals - fetal cortex later replaced by adult cortex
  • Week 6 - fetal cortex, from mesothelium adjacent to dorsal mesentery; Medulla, neural crest cells from adjacent sympathetic ganglia
  • Adult cortex - mesothelium mesenchyme encloses fetal cortex

Adrenal Cortex

  • Late Fetal Period - differentiates to form cortical zones
  • Birth - zona glomerulosa, zona fasiculata present
  • Year 3 - zona reticularis present

Adrenal Medulla

  • neural crest origin, migrate adjacent to coelomic cavity, initially uncapsulated and not surrounded by fetal cortex, cells have neuron-like morphology
  • 2 cell types - secrete epinepherine (adrenaline) 80%; secrete norepinepherine (noradrenaline* 20%
Adrenal medulla.jpg
 ‎‎Adrenal Medulla
Page | Play
Week 10 adrenal gland
Human fetal adrenal gland 01.jpg
Human fetal adrenal gland morphology and size.[6]
Links: Endocrinology - Adrenal Cortex Development

Adrenal Cortex

Adrenal gland (Mouse E16.5)
Human-adrenal gland 01.jpg Week10 adrenal.jpg
Human Embryo (8 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.)

Week 4 - coelomic 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).[13]

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 Cortex (week 12)

Fetal adrenal cortical growth involves several cellular processes: hypertrophy, hyperplasia, apoptosis, and migration.

In the second and third trimesters a steroid precursor dehydroepiandrosterone (DHEA) and sulphated derivative (DHEAS) which is converted by placenta into estrogen.

Three functional zones:

  1. Fetal zone - throughout gestation expresses enzymes required for DHEA-S synthesis.
  2. Transitional zone - initially identical to the fetal zone but later (after 25-30 weeks) expresses enzymes that suggest glucocorticoid synthesis.
  3. Definitive zone - after 22-24 weeks expresses enzymes that suggest mineralocorticoid synthesis.


  • human males produce high levels of DHEA) and DHEAS
  • decline within a few months of birth
  • due to regression of the adrenal fetal zone


  • zona reticularis (ZR) source for production of DHEA and DHEAS

Adult Cortex

Endocrine pathway: Hypothalamus-Pituitary-Adrenal

Development of the early adult cortex (Fetal week 12)

Early Adult Cortex (week 12)

  • Reticularis - narrow band, many small cells and capillaries androgens. source for production of DHEA and DHEAS
  • Fasiculata - high lipid content, pale foamy cells cortisol, corticosterone, cortisone.
  • Glomerulosa - small cells, cords or oval groups, aldosterone.

Animal Models


mouse Medulla[2]

  • preganglionic axons direct chromaffin cell precursors into the adrenal primordia.
  • guidance cues using class 3 semaphorin (SEMA3) signalling through neuropilins (NRP).

rat Medullary Timeline[14]

  • day 13 to 15 - chromaffin cells migrate from a group of TH-positive cells present dorsal to the adrenal primordium via the medial cranial end of the adrenal primordium into the adrenal primordium.
  • after 16 days - adrenal capsule formed, except on the ventral aspect of the cranial end of the adrenal gland, from which TH-positive cells penetrated into the adrenal gland.
  • neural crest cells may use the same pathway to migrate to the sympathetic chain ganglia dorsal to the adrenal gland, to the adrenal gland, and to the preaortic ganglion.


Species Cortex Difference

  • rat - zona glomerulosa and zona fasciculata separated by an undifferentiated zone (ZU, or Zona Intermedia)
  • mouse - no undifferentiated zone separation.
    • capsule mesenchyme cells have properties of adrenocortical stem/progenitor cells.

Adult Histology

Adrenal Histology: Cortex and Medulla | Unlabelled Overview | Cortical Zones | Zona Glomerulosa and Fasciculata | Zona Glomerulosa | Zona Fasciculata | Zona Reticularis and Medulla | Zona Reticularis | Medulla | Fetal Cortex | Developing Adult Cortex | BGD - Endocrine Histology | Histology Stains | Adrenal Development


Semaphorin - Neuropilin

A recent study has shown that preganglionic axons and chromaffin cell precursors require class 3 semaphorin (SEMA3) signalling through neuropilins (NRP) to target the adrenal medulla.[2]

  • Semaphorin A3 (SEMA3, 7q21.11) member of the emaphorin protein family, with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. The secreted protein can have different neuronal patterning functions:
    • chemorepulsive - inhibiting axonal outgrowth.
    • chemoattractive - stimulating the growth of apical dendrites.
  • Neuropilin 1 (NRP1, 10p11.22) and Neuropilin 2 (NRP2, 2q33.3) - membrane-bound co-receptor for tyrosine kinase receptor for both vascular endothelial growth factor (Template:VEGF;) and semaphorin (SEMA3A) family members. These 2 neuropilins have many different roles in tissues including: angiogenesis, axon guidance, cell survival, migration, and invasion.

OMIM Links: SEMA3 | NRP1 | NRP2

Steroidogenic Factor 1

Adrenal and gonad steroidogenic factor 1 expression.jpg

Adrenal and gonad steroidogenic factor 1 (SF-1) expression in different species [15]

  • 53 kDa protein called Ad4BP (Adrenal 4 Binding Protein) or SF-1 (Steroidogenic Factor 1)
  • classical DNA-binding domain (DBD) characterized by two Cys2-Cys2 zinc fingers in the N-terminal region
  • SF-1 binds DNA as a monomer
  • high homology with the drosophila Ftz-F1 transcription factor that controls fushi tarazu homeotic gene expression

Steroidogenic Factor 1 Mutation Effects

Genotype SF-1 -/- SF-1 +/- SF-1 -/+ or SF-1 -/-
Adrenal Agenesis Histological defects

Hyporesponse to stress

Compensatory growth defects

Insufficiency (agenesis or dysgenesis)
Testis Agenesis

Sex reversal

Sex reversal
Ovary Agenesis Normal
Ventro-Medial Hypothalamus Agenesis

Obesity caused by absence of the VMH (8 weeks)

Pituitary Defects of gonadotrope cells

Table modified from review.[15]


Sry-box (Sox) 8, and Sox10 are expressed in the neural crest and in neural crest cells migrating to the adrenal gland.[16]




Congenital Adrenal Hyperplasia

 ICD-11 Congenital adrenal hyperplasia - Congenital adrenal hyperplasia (CAH) refers to a group of diseases associated with either complete (classical form) or partial (non-classical) anomalies in the biosynthesis of adrenal hormones. The disease is characterized by insufficient production of cortisol, or of aldosterone (classical form with salt wasting), associated with overproduction of adrenal androgens. In the classical form, metabolic decompensation (dehydration with hyponatremia, hyperkalemia and acidosis associated with mineralocorticoid deficiency, and hypoglycemia associated with glucocorticoid deficiency) may be life-threatening from the neonatal period onwards. Genital anomalies may be noted at birth in affected females.

The adrenal abnormality of congenital adrenal hyperplasia (CAH) is a family of inherited disorders of adrenal steroidogenesis enzymes which impairs cortisol production by the adrenal cortex. In the literature this abnormality has also been called: Congenital adrenogenital disorders associated with enzyme deficiency, congenital adrenal cortical hyperplasia, congenital adrenal gland hyperplasia, congenital adrenogenital syndrome, congenital, hyperadrenocorticism, congenital adrenogenitalism and congenital female adrenal pseudohermaphroditism.

Enzymes most commonly affected: 21-hydroxylase (21-OH), 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase.

Enzymes less commonly affected: 17 alpha-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.

Congenital Adrenal Hyperplasia
Type Enzyme Deficiency Female Male
classic virilizing adrenal hyperplasia 21-hydroxylase, 11-beta-hydroxylase,
or 3-beta-hydroxysteroid dehydrogenase
ambiguous genitalia at birth - complete or partial fusion of the labioscrotal folds and a phallic urethra to clitoral enlargement (clitoromegaly), partial fusion of the labioscrotal folds, or both normal genitalia, present at age 1-4 weeks with salt wasting (classic salt-wasting adrenal hyperplasia)
simple virilizing adrenal hyperplasia mild 21-hydroxylase identified later in childhood because of precocious pubic hair, clitoral enlargement (clitoromegaly), or both, often accompanied by accelerated growth and skeletal maturation early genital development (pubic hair and/or phallic enlargement) accelerated growth and skeletal maturation
nonclassic adrenal hyperplasia milder deficiencies of 21-hydroxylase
or 3-beta-hydroxysteroid dehydrogenase
present at puberty or adult with infrequent menstruation (oligomenorrhea), abnormal hair growth (hirsutism), and/or infertility
17-hydroxylase deficiency syndrome 17-hydroxylase deficiency or

3-beta-hydroxysteroid dehydrogenase

rare, phenotypically female at birth do not develop breasts or menstruate in adolescence and may have hypertension steroidogenic acute regulatory (StAR) deficiency have ambiguous genitalia or female genitalia, at puberty may lack breast development and may have hypertension
This is a complex steroidogenic abnormality, and the above table of clinical descriptions are provided only a guide.
Links: Genital Abnormalities | Adrenal Development | Genes and Disease | OMIM 21 Deficiency | OMIM 17 Deficiency | OMIM 3 Deficiency

Links: genital abnormalities


(PCC) A rare catecholamine-producing (neuro)endocrine tumor located in the adrenal medulla. Similar catecholamine-producing tumors outside the adrenal gland are called paragangliomas (PGL). A recent study has looked at the impact of maternal pheochromocytoma on the fetus and neonate[17]: "Fetal risks are mainly determined by the vasoconstrictive effects of maternal catecholamine on uteroplacental circulation, because the fetus is protected from the direct effects of high catecholamine levels at the placental interface. Uteroplacental insufficiency may lead to spontaneous abortion, fetal growth restriction, premature delivery, and fetal hypoxia, followed by fetal distress and/or birth asphyxia."

Links: placenta

Cushing's Syndrome

(hypercortisolism) A relatively rare metabolic hormonal disorder caused by prolonged exposure of the body’s tissues to high levels of the adrenal hormone cortisol, most commonly affects adults aged between 20 to 50 and also the obese with type 2 diabetes.

Links: NIH National Endocrine and Metabolic Diseases - Cushing’s Syndrome

Adrenocortical Tumour

Childhood adrenocortical tumours distribution by age and gender (n=125)[18]

Adrenocortical tumours (ACT) can occur at all ages and have a bimodal distribution with peaks of incidence at about 5 years of age and again at 40 to 50 years of age. Clinically, a routine hormonal profile for suspected patients includes measurements of serum (8am, 11pm) cortisol, testosterone, DHEA-S, androstenedione, 17-hydroxyprogesterone, aldosterone, and plasma renin activity.[18]


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Online Textbooks

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


Asby DJ, Arlt W & Hanley NA. (2009). The adrenal cortex and sexual differentiation during early human development. Rev Endocr Metab Disord , 10, 43-9. PMID: 18670886 DOI.

Ferraz-de-Souza B & Achermann JC. (2008). Disorders of adrenal development. Endocr Dev , 13, 19-32. PMID: 18493131 DOI.

Hanley NA & Arlt W. (2006). The human fetal adrenal cortex and the window of sexual differentiation. Trends Endocrinol. Metab. , 17, 391-7. PMID: 17046275 DOI.

Huber K. (2006). The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev. Biol. , 298, 335-43. PMID: 16928368 DOI.

Yanase T, Gondo S, Okabe T, Tanaka T, Shirohzu H, Fan W, Oba K, Morinaga H, Nomura M, Ohe K & Nawata H. (2006). Differentiation and regeneration of adrenal tissues: An initial step toward regeneration therapy for steroid insufficiency. Endocr. J. , 53, 449-59. PMID: 16807499

Jaffe RB, Mesiano S, Smith R, Coulter CL, Spencer SJ & Chakravorty A. (1998). The regulation and role of fetal adrenal development in human pregnancy. Endocr. Res. , 24, 919-26. PMID: 9888597

Mesiano S & Jaffe RB. (1997). Developmental and functional biology of the primate fetal adrenal cortex. Endocr. Rev. , 18, 378-403. PMID: 9183569 DOI.


Speiser PW. (2010). Growth and development: congenital adrenal hyperplasia-glucocorticoids and height. Nat Rev Endocrinol , 6, 14-5. PMID: 20010965 DOI.

Hui XG, Akahira J, Suzuki T, Nio M, Nakamura Y, Suzuki H, Rainey WE & Sasano H. (2009). Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence. J. Endocrinol. , 203, 241-52. PMID: 19723922 DOI.

Val P, Martinez-Barbera JP & Swain A. (2007). Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development , 134, 2349-58. PMID: 17537799 DOI.

Goto M, Piper Hanley K, Marcos J, Wood PJ, Wright S, Postle AD, Cameron IT, Mason JI, Wilson DI & Hanley NA. (2006). In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J. Clin. Invest. , 116, 953-60. PMID: 16585961 DOI.

Villa-Cuesta E & Modolell J. (2005). Mutual repression between msh and Iro-C is an essential component of the boundary between body wall and wing in Drosophila. Development , 132, 4087-96. PMID: 16093324 DOI.

Boglione L, Bondone C, Corno E, Gastaldo L, Borghi F, Gattolin A & Levi AC. (2001). The development of the suprarenal gland: surgical and anatomical considerations. Panminerva Med , 43, 33-7. PMID: 11319516

Jaffe RB, Mesiano S, Smith R, Coulter CL, Spencer SJ & Chakravorty A. (1998). The regulation and role of fetal adrenal development in human pregnancy. Endocr. Res. , 24, 919-26. PMID: 9888597

"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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Endocrine Terms (expand to view) 
  • adenohypophysis - (anterior pituitary, pars distalis) anterior part of pituitary embryonic development from surface ectoderm adenohypophyseal placode. Placode folds inward on the roof of the pharynx forming a transient structure Rathke's pouch.
  • adrenocorticotropin - (ACTH or corticotropin) anterior pituitary, peptide hormone stimulates the adrenal cortex to produce corticosteroid hormones — primarily cortisol — as well as small amounts of female and male sex hormones.
  • androstenedione - hormone precursor of testosterone and other steroidal androgens.
  • atrial natriuretic peptide - (ANP) heart, peptide hormone regulates blood pressure. A study suggests that its activating enzyme corin, and ANP together, have a role in placentation, by promoting trophoblast invasion and spiral artery remodelling. (PMID 22437503)
  • basophil cell - pituitary named by histological staining (deep blue, purple) different types produce different hormones: corticotrophs (ACTH, CRH), gonadotrophs (FSH, LH, GnRH), and thyrotrophs (TSH, TRH). See acidophil and chromophore cells.
  • C cells - parafollicular cells of the thyroid.
  • calcitonin - (CT) C cells of thyroid, peptide hormone thyroid
  • corpus luteum - ovarian endocrine organ from ovulating follicle, stimulated by hCG and supports early pregnancy by secreting progesterone, 17β-progesterone, estradiol and androstenedione.
  • corticosteroid binding globulin - (CBG) binds and transports glucocorticoids in the plasma. Globin is synthesised in the liver. adrenal
  • dihydrotestosterone - (DHT) steroidal hormone made locally by 5-alpha reductase conversion of testosterone into a more active form in genital effects.
  • dehydroepiandrosterone - (DHEA, androstenolone) adrenal cortex, gonads and brain make this steroid intermediate that may also have adult hormonal functions.
  • dehydroepiandrosterone sulphate - (DHEAS, DHEA-S) fetal adrenal cortex makes this inactive precursor of a steroid hormone.
  • dydrogesterone - clinical oral retrosteroid structurally related to progesterone, with a greater bioavailability and selectivity for the progesterone receptor.
  • estrogen (oestrogen) family of female steroidal hormones - estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4) synthesised from testosterone and androstenedione, by aromatase. Also produced in male testis, and required for genital development (PMID 29438493)
  • estrone (E1) - steroid hormone with weak estrogenic activity.
  • estradiol (E2) - (oestradiol) estrogen steroid hormone with main estrogenic female activity.
  • estriol (E3) - (oestriol) steroid hormone with weak estrogenic activity.
  • estetrol (E4) (oestetrol) steroid hormone with weak estrogenic activity produced only during pregnancy.
  • follicle stimulating hormone - (FSH) pituitary glycoprotein hormone secreted by gonadotrophs (basophilic cell subgroup) acts on gametogenesis and other systems in both males and females. Females, acts on the ovary to stimulate follicle development. Negative feedback by inhibin from the developing follicle decreases FSH secretion. Males, acts on the testis Sertoli cells to increase androgen-binding protein (ABP) that binds androgens and has a role in spermatogenesis.
  • growth hormone - (GH) pituitary, peptide hormone that stimulates tissue and skeletal growth. In the ovary, growth hormone also increases granulosa cell FSH-dependent E2 production.
  • growth hormone releasing hormone - (GHRH) hypothalamus‎, protein that activates growth hormone synthesis and release from the anterior pituitary.
  • human chorionic gonadotropin - (hCG) glycoprotein hormone with 2 subunits (alpha and beta joined non covalently). Similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents (regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG). PMID 19171054
  • human chorionic somatommotropin - (hCS, CSH, placental lactogen) Placental hormone is structurally similar to both growth hormone (GH) and prolactin (PRL} and binds strongly to PRL receptors but weakly to GH receptors. Role in stimulating maternal mammary gland development. endocrine placenta
  • interstitial cell - (Leydig cell) Male testis cell secrete the androgen testosterone, required for fetal male genital tract differentiation and masculinisation after puberty.
  • Leydig cell - (interstitial cell) Male testis cell secrete the androgen testosterone, beginning in the fetus. These cells are named after Franz von Leydig (1821 - 1908) a German scientist who histologically described these cells.
  • lutenizing hormone - (LH, gonadotropin, lutropin, Interstitial Cell Stimulating Hormone, ICSH) pituitary, glycoprotein hormone acts on the gonad and has a role in male and female reproduction. Female, increase in concentration during the menstrual cycle triggers ovulation. Male, stimulates testis interstital cell production of testosterone. Gonadotrophins have been used clinically in humans for the treatment of female infertility.
  • melaocyte stimulating hormone - (MSH) pituitary, peptide hormone pituitary
  • melatonin - (N-acetyl-5-methoxytryptamine) pineal amino acid amino (precursor tryptophan) hormone involved with the diurnal cycle, melatoinin levels are high in dark, low in daylight. Also acts as an antioxidant, free radical scavenger, and anti-inflammatory molecule.
  • prolactin - (PRL) pituitary, peptide hormone pituitary
  • parathyroid - endocrine gland through parathyroid hormone (PTH) regulates calcium and phosphate levels in conjunction with parafollicular cells of the thyroid gland (calcitonin) and Vitamin D, dietary or synthesized in the skin. Develops from pharyngeal endoderm, in this case the 3rd and 4th pharyngeal pouches.
  • parathyroid hormone - (PTH) parathyroid, peptide hormone parathyroid
  • synthetic ACTH test = (synacthen test) A diagnostic test to both measure the amount of cortisol in the body and to determine the ability to produce cortisol.
  • testosterone - testis ovary steroidal hormone. In males is the androgen which regulates genital (gonadal and tract), secondary sex characteristics and neural development. The steroid is converted to the active metabolite dihydrotestosterone (DHT) by the enzyme 5-alpha reductase for the genital effects and estradiol by the enzyme aromatase for the neural effects.
  • thyroid - endocrine gland located in the neck with a developmental role in neurological development and metabolism.
  • thyroid diverticulum - the primordium of the thyroid gland, beginning as an median endodermal thickening in the floor of pharynx between the pharyngeal pouch 1 and 2.
  • thyroid hormone - (TH) thyroid amino acid derivative with two main forms (T3, T4) regulates tissue metabolic activity.
  • thyroid stimulating hormone - (TSH) pituitary protein hormone
  • ultimobranchial body - historic term for the embryonic structure that forms the parafollicular cells (C cells) of the thyroid.
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