Endocrine System Development

Introduction

Human adrenal gland (Week 10)

The endocrine system resides within specific endocrine organs and both organs and tissues with other specific functions. Epithelia (ectoderm and endoderm) form the majority of the “ductless” endocrine glands like gastrointestinal and skin associated “ducted” glands. Differentiation of several also organs involves a epithelial/mesenchye interaction, seen in repeated in many differentiation of many different tissues. The endocrine glands produce hormones, which are distributed by the vascular system to the many body tissues, subsequently these organs are richly vascularized.

Hormones are recognised by either cell surface receptors (modified amino acids, peptides, proteins) or cytoplasmic/nuclear receptors (steroids). Hormones “orchestrate” responses in other tissues, including other endocrine organs, and these overall effects can be similar or different in different tissues. In addition, these hormone effects (like music) can be rapid, slow, brief, diurnal, or long-term. Hormone effects can be mimicked, stimulated, and blocked by therapeutic drugs, nutritional and environmental chemicals.

The human fetus is dependent upon endocrine development for hormones, which support normal development. Peripheral endocrine glands (thyroid, pancreas, adrenals, gonads) form early in the second month from epithelial/mesenchye interactions and differentiate into the third month. The fetus also has a unique hormonal system that combines not only its own developing endocrine system, but also that of the placenta and maternal hormones.

Abnormal endocrine development/function can impact on many different systems. For example, insufficient maternal dietary iodine impacts on fetal thyroid gland thyroid hormone production, which in turn can lead to abnormal neural development. Alternatively, we now know many environmental and therapeutic chemicals have a wide range of effects on the endocrine system.

Sex hormones from the gonads have significant effects prenatally and postnatally, specifically at puberty with a role to play in male/female biological maturity and have wide actions throughout the body.

This current page provides a general introduction to the endocrine system, use the links below to explore development of specific endocrine organs.

| original page

Some Recent Findings

Endocrine Pancreas "The transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing alpha-cells as this cell type is absent in the mutants." Pituitary Gland Development recent review article looking at molecular mechanisms of development.

Textbooks

In general, not dealt with as a system in many embryology textbooks, so various chapters: nervous system, head, gastrointestinal tract, reproductive organs, etc. See the online Endocrinology textbook for better descriptions of these tissues.

• Endocrinology - An Integrated Approach Stephen Nussey and Saffron Whitehead, St. George's Hospital Medical School, London, UK Oxford: BIOS Scientific Publishers; 2001. ISBN-10: 1-85996-252-1 Copyright © 2001, BIOS Scientific Publishers Limited. [Endocrine_System_Development#Textbooks_2|Table of contents] | Bookshelf Link
• Human Embryology (3rd ed.) Larson Chapter 9 Gastrointestinal, Chapter 10 Gonad, Kidney Chapter 12 Head
• The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapters 10: p230-233; Ch12: p280-282; Ch13: p319-347
• Lectures - 2010 | 2009 | 2008 | Medicine Lecture - Endocrine Development

| original Endocrine page

Objectives

• Understand the main steps in the development of the thyroid, parathyroid, adrenal, pituitary, pineal glands, thymus and gonads.
• Have a general understanding of the chief functions of these endocrine organs.
• Understand the endocrine contribution to embryo development.
• Understand the endocrine role of the placenta during development.
• Have a general understanding of different types of hormones and their signaling actions.

Hormones

Steroid hormone receptor signaling

Hormone Types

Steroid biosynthesis pathway

• Amino acid derivatives - noradrenaline (norepinepherine), adrenalin (epinepherine) , thyroid hormone
• Proteins, peptides - thyroid stimulating hormone, leutenising hormone, follicle stimulating hormone
• Steroids - androgens, glucocorticoids, mineralocorticoids

Hormone Actions

• Autocrine - acts on self (extracellular fluid)
• Paracrine - acts locally (extracellular fluid)
• Endocrine - acts by secretion into blood stream (endocrine organs are richly vascularized)

Hormone Receptors

Hormones are recognised by either cell surface receptors (modified amino acids, peptides, proteins) or cytoplasmic/nuclear receptors (steroids).

Endocrine Origins

• Derived from epithelia - covering embryo, lining gastrointestinal tract, lining coelomic cavity
• Also mesenchymal contribution

Development Overview

See specific endocrine organ development.

Pineal Gland

Adult pineal body

Pineal gland position

• part of epithalmus - neurons, glia and pinealocytes
• pinealocytes secrete melatonin - cyclic nature of activity, melatonin lowest during daylight
  • inhibit hypothalamic secretion of GnRH until puberty, pineal gland then rapidly regresses.
• other activities - possibly gamete maturation, antioxidant effect, protect neurons?

Pineal Development

• Neuroectoderm - prosenecephalon then diencephalon
• caudal roof, median diverticulum, epiphysis
• Initially a hollow diverticulum, cell proliferation to solid, pinealocytes (neuroglia), cone-shaped gland innervated by epithalmus

Links: Endocrine - Pineal Development

Hypothalamus

Hormones - Thyrotrophin releasing hormone (TRH), Corticotrophin releasing hormone (CRH), Arginine vasopressin (AVP), Gonadotrophin releasing hormone (GnRH), Growth hormone releasing hormone (GHRH), Somatostatin, Prolactin relasing factor (PRF), Dopamine

Hypothalamus Development

• Neuroectoderm - prosenecephalon then diencephalon
• ventro-lateral wall intermediate zone proliferation
• Mamillary bodies - form pea-sized swellings ventral wall of hypothalamus

Links: Endocrine - Hypothalamus Development

Pituitary

Adult pituitary

Anterior pituitary hormones - Thyroid-stimulating hormone (TSH), Adrenocorticotrophic hormone (ACTH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), Somatotrophin/growth hormone (GH), Prolactin (PRL), Melanocyte-stimulating hormone (MSH)

Posterior pituitary hormones - Oxytocin, Arginine vasopressin

Pituitary Development

Pituitary rabbit development

Blue - neural tube ectoderm Red - surface ectoderm

• Dual ectoderm origins
  • Ectoderm - ectoderm roof of stomodeum, Rathke's pouch, adenohypophysis
  • Neuroectoderm - prosenecephalon then diencephalon, neurohypophysis

Adenohypophysis

• Anterior wall proliferates - pars distalis
• Posterior wall little growth – pars intermedia
• Rostral growth around infundibular stem – pars tuberalis

Neurohypophysis

• Infundibulum – median eminence, infundibulum, pars nervosa

Pituitary Timeline

• Week 4 - hypophysial pouch, Rathke’s pouch, diverticulum from roof
• Week 5 - elongation, contacts infundibulum, diverticulum of diencephalon
• Week 6 - connecting stalk between pouch and oral cavity degenerates
• Week 10 - growth hormone and ACTH detectable
• Week 16 - adenohypophysis fully differentiated
• Week 20 to 24 - growth hormone levels peak, then decline

Links: Endocrine - Pituitary Development | Embryo Images - Pituitary

Thyroid

• Functions from wk10, required for neural development, stimulates metabolism (protein, carbohydrate, lipid), reduced/absence = cretinism (see abnormalities)

Hormones - (amino acid derivatives) Thyroxine (T4), Triiodothyronine (T3)

Thyroid Development

Stage 13 and Stage 22 thyroid development

foramen caecum

• thyroid median endodermal thickening in the floor of pharynx, outpouch – thyroid diverticulum
• tongue grows, cells descend in neck
• thyroglossal duct - proximal end at the foramen cecum of tongue thyroglossal duct
• thyroid diverticulum - hollow then solid, right and left lobes, central isthmus

Thyroid Timeline

• 24 days - thyroid median endodermal thickening in the floor of pharynx, outpouch – thyroid diverticulum
• Week 11 - colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis

growth factors (insulin-like, epidermal) stimulates follicular growth

Fetal Thyroid Hormone

• Initial secreted biologically inactivated by modification, late fetal secretion develops brown fat
• Iodine deficiency- during this period, leads to neurological defects (cretinism)
• Birth - TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels

Links: Endocrine - Thyroid Development

Parathyroid

Parathyroid adult

• Parathyroid Hormone - Increase calcium ions [Ca2+], stimulates osteoclasts, increase Ca GIT absorption (opposite effect to calcitonin)
• Adult Calcium and Phosphate - Daily turnover in human with dietary intake of 1000 mg/day
• secreted by chief cells

Principal cells cords of cells

Parathyroid Development

Pharyngeal pouches

• Endoderm - third and fourth pharyngeal pouches, could also have ectoderm and neural crest
  • 3rd Pharyngeal Pouch - inferior parathyroid, initially descends with thymus
  • 4th Pharyngeal Pouch - superior parathyroid
• Week 6 - diverticulum elongate, hollow then solid, dorsal cell proliferation
• Fetal parathyroids - respond to calcium levels, fetal calcium levels higher than maternal

Links: Endocrine - Parathyroid Development

Thymus

• Thymus - bone-marrow lymphocyte precursors become thymocytes, and subsequently mature into T lymphocytes (T cells)
• Thymus hormones - thymosins stimulate the development and differentiation of T lymphocytes

Thymus Development

• Endoderm - third pharyngeal pouch
• Week 6 - diverticulum elongates, hollow then solid, ventral cell proliferation
• Thymic primordia - surrounded by neural crest mesenchyme, epithelia/mesenchyme interaction

Links: Endocrine - Thymus Development

Pancreas

Pancreas adult

pancreas structure

• Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume
• Exocrine function - begins after birth
• Endocrine function - from 10 to 15 weeks onward hormone release
  • exact roles of hormones in regulating fetal growth?

Pancreas Development

Pancreatic buds and duct developing

Stage22 pancreas

• Pancreatic buds - duodenal level endoderm, splanchnic mesoderm forms dorsal and ventral mesentery, dorsal bud (larger, first), ventral bud (smaller, later)
• Pancreas Endoderm - pancreas may be opposite of liver
  • Heart cells promote/notochord prevents liver formation
  • Notochord may promote pancreas formation
  • Heart may block pancreas formation

• Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds
• Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function
• Islet cells - cords of endodermal cells form ducts, from which cells bud off to form islets

Pancreatic Islets

• Islets of Langerhans - 4 endocrine cell types
• Alpha - glucagon, mobilizes lipid
• Beta - insulin, increase glucose uptake
  • Beta cells, stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant
• Delta - somatostatin, inhibits glucagon, insulin secretion
• F-cells - pancreatic polypeptide

Pancreas Timeline

• Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin
• Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins
• Week 15 - glucagon detectable in fetal plasma

Links: Endocrine - Pancreas Development | Gastrointestinal Tract - Pancreas Development

Adrenal

• 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

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%

Links: Endocrine - Adrenal Development

Gonad

Female HPG axis

HPG Axis - Endocrinology - Simplified diagram of the actions of gonadotrophins

Gonad Development

• mesoderm - mesothelium and underlying mesenchyme, primordial germ cells
• Gonadal ridge - mesothelium thickening, medial mesonephros
• Primordial Germ cells - yolk sac, to mesentery of hindgut, to genital ridge of developing kidney

Differentiation

• testis-determining factor (TDF) from Y chromosome: presence (testes), absence (ovaries)

Testis

• 8 Weeks, mesenchyme, interstitial cells (of Leydig) secrete testosterone, androstenedione
• 8 to 12 Weeks - hCG stimulates testosterone production
• Sustentacular cells - produce anti-mullerian hormone to puberty

Ovary

• X chromosome genes regulate ovary development

Links: Endocrine - Gonad Development

Placenta

Trophoblast hCG function

• Human chorionic gonadotrophin (hCG) - like leutenizing hormone, supports corpus luteum in ovary, pregnant state rather than menstrual, maternal urine in some pregnancy testing

• Human chorionic somatommotropin (hCS) - or placental lactogen stimulate (maternal) mammary development
• Human chorionic thyrotropin (hCT)
• Human chorionic corticotropin (hCACTH)
• progesterone and estrogens - support maternal endometrium
• Relaxin

• Placenta - Maternal (decidua) and Fetal (trophoblastic cells, extraembryonic mesoderm) components
• Endocrine function - maternal and fetal precursors, synthesis and secretion
  • Protein Hormones - chorionic gonadotropin (hCG), chorionic somatomammotropin (hCS) or placental lactogen (hPL), chorionic thyrotropin (hCT), chorionic corticotropin (hCACTH)
    • hCG - up to 20 weeks, fetal adrenal cortex growth and maintenance
    • hCS – rise through pregnancy, stimulates maternal metabolic processes, breast growth
  • Steroid Hormones - progesterone (maintains pregnancy), estrogens (fetal adrenal/placenta)

Links: Endocrine - Placenta Development

Other Endocrine

Endocrine Heart

• Atrial natriuretic peptide (ANP) - Increase Filtration rate / decrease Na+ reabsorption
• Endothelins - ET-1, ET-2, ET-3, Vasoconstriction / Increase NO
• Nitric oxide (NO) - Vasodilatation

Endocrine Kidney

• Renin - Increase Angiotensin-aldosterone system
• Prostaglandins - decrease Na+ reabsorption
• Erythropoietin - Increase Erythrocyte (rbc) production
• 1,25 (OH)2 vitamin D - calcium homeostasis
• Prekallikreins - Increase Kinin production

GIT Endocrine

Enteric control of digestive function

• Gastrin - Secreted from stomach (G cells), role in control of gastric acid secretion
• Cholecystokinin - small intestine hormone, stimulates secretion of pancreatic enzymes and bile
• Secretin - small intestine hormone (epithelial cells), stimulates secretion of bicarbonate-rich fluids from pancreas and liver

Adipose Tissue

• Leptin - polypeptide hormone produced in adipose and many other tissues with also many different roles
• Adiponectin - regulation of energy homeostasis and glucose and lipid metabolism, as well as acting as an anti-inflammatory on the cellular vascular wall
• Resistin - (for resistance to insulin, RETN) a 108 amino acid polypeptide and the related resistin-like protein-beta (Resistin-like molecule-beta, RELMbeta) stimulate endogenous glucose production

Links: Endocrine - Other Tissues

Endocrine Functional Changes

• Puberty - Increased activity
• Menopause - Decreased activity
• Disease - (diabetes, thyroid, kidney) suggested trends that genetics, health, nutrition, lifestyle may influence time that these events occur
• Pharmaceutical impact - birth control, steroids, Hormone Replacement Therapy (HRT)

References

Textbooks

Endocrinology - An Integrated Approach Stephen Nussey and Saffron Whitehead, St. George's Hospital Medical School, London, UK Oxford: BIOS Scientific Publishers; 2001. ISBN-10: 1-85996-252-1 Copyright © 2001, BIOS Scientific Publishers Limited. Bookshelf Link

• Chapter 1. Principles of endocrinology
• Chapter 2. The endocrine pancreas
• Chapter 3. The thyroid gland
• Chapter 4. The adrenal gland
• Chapter 5. The parathyroid glands and vitamin D
• Chapter 6. The gonad
• Chapter 7. The pituitary gland
• Chapter 8. Cardiovascular and renal endocrinology

Reviews

<pubmed>21448326</pubmed>

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Search April 2010

• Endocrine Development - All (14277) Review (4620) Free Full Text (3140)

Search Pubmed: Endocrine Development

Additional Images

Embryonic Histology

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  Stage 22 - Pancreatic duct

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  Stage 22 - Adrenal gland

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  Week 10 - Adrenal gland

Adult Histology

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  Pineal (high power)

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  Thyroid (low power)

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  Thyroid (high power)

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  Parathyroid (low power)

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  Parathyroid (high power)

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  Pituitary - adenohypophysis

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  Pituitary - adenohypophysis

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  Pituitary - neurohypophysis

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  Adrenal - Cortex and Medulla

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  Adrenal - Cortical Zones

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  Adrenal - Zona Reticularis and Medulla

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  Pancreatic islet

Glossary Links

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Cite this page: Hill, M.A. (2024, May 5) Embryology Endocrine System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_System_Development

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