Endocrine - Adrenal Development

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.

| Lecture - Neural Crest Development | original page

• 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

Adrenal 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.

Adrenal medullary hormones - (amino acid derivatives) Epinephrine, Norepinephrine

Some Recent Findings

Migration and distribution of neural crest-derived cells in the human adrenal cortex at 9-16 weeks of gestation "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. "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."

Adrenal Development

Week 10 adrenal gland

• 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

Endocrinology - Adrenal Cortex Development

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%

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. (More? [#Medulla 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? [#Cortex Adrenal Cortex])

Adrenal Cortex

Adrenal gland (Mouse E16.5)

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).

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 (DEA) 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.

Adult Cortex

Early Adult Cortex (week 12)

• 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.

Adult Histology

• 

  Adrenal - Cortex and Medulla

• 

  Adrenal - Cortical Zones

• 

  Adrenal - Zona Reticularis and Medulla

• 

  Adrenal - Zona Glomerulosa and Fasciculata

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: 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.

Links: Genital System - Abnormalities | Genital System Development

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 - NIDDK

Adrenocortical Tumour

[[File:Childhood adrenocortical tumours graph.jpg|thumb|Childhood adrenocortical tumours distribution by age and gender (n=125) 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.

Genes

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

• SF-1 - Steroidogenic factor 1 an orphan nuclear receptor

• DAX1

• CYP17

References

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

<pubmed>18670886</pubmed> <pubmed>18493131</pubmed> <pubmed>17046275</pubmed> <pubmed>16928368</pubmed> <pubmed>16807499</pubmed> <pubmed>9888597</pubmed> <pubmed>9183569</pubmed>

Articles

<pubmed>20010965</pubmed> <pubmed>19723922</pubmed> <pubmed>17537799</pubmed> <pubmed>16585961</pubmed> <pubmed>16093324</pubmed> <pubmed>11319516</pubmed> <pubmed>9888597</pubmed>"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."

Search PubMed

Search April 2010

• Adrenal Development - All (646) Review (52) Free Full Text (84)

• Congenital Adrenal Hyperplasia - All (2091) Review (211) Free Full Text (314)

Search Pubmed: adrenal development | Congenital Adrenal Hyperplasia

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

---

Cite this page: Hill, M.A. (2024, May 2) Embryology Endocrine - Adrenal Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Adrenal_Development

What Links Here?

© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G