Endocrine - Adrenal Development

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Introduction

Adrenal Gland (week 10)

The developing adrenal gland has both an interesting origin and an intruiging 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 the maturation of the lung and other developing systems.


Endocrine Links: Introduction | BGD Lecture | Science Lecture | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1904 interstitial Cells | 1908 Pancreas Different Species | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1937 Pineal | 1938 Parathyroid | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus
| Lecture - Neural Crest Development

Some Recent Findings

  • Fetal adrenal gland in the second half of gestation: morphometrical assessment with 3.0T post-mortem MRI[1]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."
  • A morphometric study of suprarenal gland development in the fetal period[2] "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[3] "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.[4] "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[5] "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)
More recent papers  
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Search term: Adrenal Embryology

Karol Jopek, Piotr Celichowski, Marta Szyszka, Marianna Tyczewska, Paulina Milecka, Ludwik K Malendowicz, Marcin Rucinski Transcriptome Profile of Rat Adrenal Evoked by Gonadectomy and Testosterone or Estradiol Replacement. Front Endocrinol (Lausanne): 2017, 8;26 PubMed 28261157

Jan Tuma, Yaroslav Kolinko, Dana Jelinkova, Pascal Hilber, Jan Cendelin Impaired spatial performance in cerebellar-deficient Lurcher mice is not associated with their abnormal stress response. Neurobiol Learn Mem: 2017; PubMed 28213063

Andreas R Janecke, Ruijuan Xu, Elisabeth Steichen-Gersdorf, Siegfried Waldegger, Andreas Entenmann, Thomas Giner, Iris Krainer, Lukas A Huber, Michael W Hess, Yaacov Frishberg, Hila Barash, Shay Tzur, Nira Schreyer-Shafir, Rivka Sukenik-Halevy, Tania Zehavi, Annick Raas-Rothschild, Cungui Mao, Thomas Müller Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. Hum. Mutat.: 2017; PubMed 28181337

T Tachibana, T Kodama, S Yamane, R Makino, S I Khan, M A Cline Possible role of central interleukins on the anorexigenic effect of lipopolysaccharide in chicks. Br. Poult. Sci.: 2017; PubMed 28090781

Myles Leavy, Matthias Trottmann, Bernhard Liedl, Sven Reese, Christian Stief, Benjamin Freitag, John Baugh, Giulio Spagnoli, Sabine Kölle Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights. Sci Rep: 2017, 7;39931 PubMed 28045098

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

Adrenal Development

Adrenal gland development and steroid hormone synthesis
Fetal adrenal gland steroidogenesis.jpg
Overview cartoon of changes in adrenal gland structure and steroid hormone syntesis[6]
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 PMID 9183569)

  • 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.[1]
Links: Endocrinology - Adrenal Cortex Development

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 Cortex

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

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).[7]

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.


Neonatal

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

Adult

  • 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.

Species 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

Molecular

Steroidogenic Factor 1

Adrenal and gonad steroidogenic factor 1 expression.jpg

Adrenal and gonad steroidogenic factor 1 (SF-1) expression in different species [8]

  • 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

Organism
Mouse
Human
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.[8]

SoxE

Sry-box (Sox) 8, and Sox10 are expressed in the neural crest and in neural crest cells migrating to the adrenal gland.[9]

DAX1

CYP17

Abnormalities

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: 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

Pheochromocytomas

(PCC) Catecholamine-producing (neuro)endocrine tumor located in the adrenal medulla. Similar catecholamine-producing tumors outside the adrenal gland are called paragangliomas (PGL).

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)[10]

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.[10]

References

  1. 1.0 1.1 Zhonghe Zhang, Haiwei Meng, Zhongyu Hou, Jun Ma, Lei Feng, Xiangtao Lin, Yuchun Tang, Xiaoli Zhang, Qingwei Liu, Shuwei Liu Fetal adrenal gland in the second half of gestation: morphometrical assessment with 3.0T post-mortem MRI. PLoS ONE: 2013, 8(10);e75511 PubMed 24116052 Cite error: Invalid <ref> tag; name "PMID24116052" defined multiple times with different content
  2. Gülnur Ozgüner, Osman Sulak, Esra Koyuncu A morphometric study of suprarenal gland development in the fetal period. Surg Radiol Anat: 2012, 34(7);581-7 PubMed 22430763
  3. Shogo Inoue, Baik Hwan Cho, Chang Ho Song, Mineko Fujimiya, Gen Murakami, Akio Matsubara Migration and distribution of neural crest-derived cells in the human adrenal cortex at 9-16 weeks of gestation: an immunohistochemical study. Okajimas Folia Anat Jpn: 2010, 87(1);11-6 PubMed 20715567
  4. Xiao-Gang Hui, Jun-ichi Akahira, Takashi Suzuki, Masaki Nio, Yasuhiro Nakamura, Hiroyoshi Suzuki, William E Rainey, Hironobu Sasano Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence. J. Endocrinol.: 2009, 203(2);241-52 PubMed 19723922
  5. Hitoshi Ishimoto, Robert B Jaffe Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr. Rev.: 2011, 32(3);317-55 PubMed 21051591
  6. E Chamoux, M Otis, N Gallo-Payet A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland. Braz. J. Med. Biol. Res.: 2005, 38(10);1495-503 PubMed 16172742 | Braz J Med Biol Res.
  7. Masahiro Goto, Karen Piper Hanley, Josep Marcos, Peter J Wood, Sarah Wright, Anthony D Postle, Iain T Cameron, J Ian Mason, David I Wilson, Neil A Hanley In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J. Clin. Invest.: 2006, 116(4);953-60 PubMed 16585961
  8. 8.0 8.1 Pierre Val, Anne-Marie Lefrançois-Martinez, Georges Veyssière, Antoine Martinez SF-1 a key player in the development and differentiation of steroidogenic tissues. Nucl. Recept.: 2003, 1(1);8 PubMed 14594453 | Nucl Recept.
  9. Simone Reiprich, C Claus Stolt, Silke Schreiner, Rosanna Parlato, Michael Wegner SoxE proteins are differentially required in mouse adrenal gland development. Mol. Biol. Cell: 2008, 19(4);1575-86 PubMed 18272785
  10. 10.0 10.1 Rosana Marques-Pereira, Luiz Delacerda, Hadriano M Lacerda, Edson Michalkiewicz, Fabiano Sandrini, Romolo Sandrini Childhood adrenocortical tumours: a review. Hered Cancer Clin Pract: 2006, 4(2);81-9 PubMed 20223012

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

Reviews

Daniel J Asby, Wiebke Arlt, Neil A Hanley The adrenal cortex and sexual differentiation during early human development. Rev Endocr Metab Disord: 2009, 10(1);43-9 PubMed 18670886

Bruno Ferraz-de-Souza, John C Achermann Disorders of adrenal development. Endocr Dev: 2008, 13;19-32 PubMed 18493131

Neil A Hanley, Wiebke Arlt The human fetal adrenal cortex and the window of sexual differentiation. Trends Endocrinol. Metab.: 2006, 17(10);391-7 PubMed 17046275

Katrin Huber The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev. Biol.: 2006, 298(2);335-43 PubMed 16928368

Toshihiko Yanase, Shigeki Gondo, Taijiro Okabe, Tomoko Tanaka, Hisao Shirohzu, Wuqiang Fan, Koichi Oba, Hidetaka Morinaga, Masatoshi Nomura, Kenji Ohe, Hajime Nawata Differentiation and regeneration of adrenal tissues: An initial step toward regeneration therapy for steroid insufficiency. Endocr. J.: 2006, 53(4);449-59 PubMed 16807499

R B Jaffe, S Mesiano, R Smith, C L Coulter, S J Spencer, A Chakravorty The regulation and role of fetal adrenal development in human pregnancy. Endocr. Res.: 1999, 24(3-4);919-26 PubMed 9888597

S Mesiano, R B Jaffe Developmental and functional biology of the primate fetal adrenal cortex. Endocr. Rev.: 1997, 18(3);378-403 PubMed 9183569

| Endocrine Reviews

Articles

Phyllis W Speiser Growth and development: congenital adrenal hyperplasia-glucocorticoids and height. Nat Rev Endocrinol: 2010, 6(1);14-5 PubMed 20010965

Xiao-Gang Hui, Jun-ichi Akahira, Takashi Suzuki, Masaki Nio, Yasuhiro Nakamura, Hiroyoshi Suzuki, William E Rainey, Hironobu Sasano Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence. J. Endocrinol.: 2009, 203(2);241-52 PubMed 19723922

Pierre Val, Juan-Pedro Martinez-Barbera, Amanda Swain Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development: 2007, 134(12);2349-58 PubMed 17537799

Masahiro Goto, Karen Piper Hanley, Josep Marcos, Peter J Wood, Sarah Wright, Anthony D Postle, Iain T Cameron, J Ian Mason, David I Wilson, Neil A Hanley In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J. Clin. Invest.: 2006, 116(4);953-60 PubMed 16585961

Eugenia Villa-Cuesta, Juan Modolell Mutual repression between msh and Iro-C is an essential component of the boundary between body wall and wing in Drosophila. Development: 2005, 132(18);4087-96 PubMed 16093324

L Boglione, C Bondone, E Corno, L Gastaldo, F Borghi, A Gattolin, A C Levi The development of the suprarenal gland: surgical and anatomical considerations. Panminerva Med: 2001, 43(1);33-7 PubMed 11319516

R B Jaffe, S Mesiano, R Smith, C L Coulter, S J Spencer, A Chakravorty The regulation and role of fetal adrenal development in human pregnancy. Endocr. Res.: 1999, 24(3-4);919-26 PubMed 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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Cite this page: Hill, M.A. 2017 Embryology Endocrine - Adrenal Development. Retrieved March 28, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Adrenal_Development

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