BGD Lecture - Endocrine Development

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Hypothalamus endocrine system

BGDB has 2 endocrine related lectures. The first is on endocrine histology (mainly of the HPA axis), the second is endocrine embryology (on this current page).

This lecture covers endocrine development, note that a better understanding can be made if you understand the adult function of each endocrine organ (though this will not be covered in the Lecture). Endocrine development is sometimes divided into neuroendocrine and endocrine and is also generally covered piecemeal in all embryology textbooks, so you may have to look in several different chapters to find supporting textbook information.

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 organs also 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 “orchestrate” responses in other tissues, including other endocrine organs, and these overall effects can be similar or different in different tissues. These signaling pathways are often described as "axes" the two major types are the: HPA (Hyothalamus-Pituitary-Adrenal) and HPG (Hypothalamus-Pituitary-Gonad). These hormone levels and 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. Importantly, fetal endocrine development is required for normal fetal growth and differentiation.

2019 Lecture Notes

Endocrine in the News  
Endocrine disrupting chemicals historical timeline.jpg

Papalou O, Kandaraki EA, Papadakis G & Diamanti-Kandarakis E. (2019). Endocrine Disrupting Chemicals: An Occult Mediator of Metabolic Disease. Front Endocrinol (Lausanne) , 10, 112. PMID: 30881345 DOI.

"Endocrine disrupting chemicals (EDCs), a heterogeneous group of exogenous chemicals that can interfere with any aspect of endogenous hormones, represent an emerging global threat for human metabolism. There is now considerable evidence that the observed upsurge of metabolic disease cannot be fully attributed to increased caloric intake, physical inactivity, sleep deficit, and ageing. Among environmental factors implicated in the global deterioration of metabolic health, EDCs have drawn the biggest attention of scientific community, and not unjustifiably. EDCs unleash a coordinated attack toward multiple components of human metabolism, including crucial, metabolically-active organs such as hypothalamus, adipose tissue, pancreatic beta cells, skeletal muscle, and liver. Specifically, EDCs' impact during critical developmental windows can promote the disruption of individual or multiple systems involved in metabolism, via inducing epigenetic changes that can permanently alter the epigenome in the germline, enabling changes to be transmitted to the subsequent generations. The clear effect of this multifaceted attack is the manifestation of metabolic disease, clinically expressed as obesity, metabolic syndrome, diabetes mellitus, and non-alcoholic fatty liver disease."

Thyroid signaling - endocrine-disrupting chemicals.jpg

Ghassabian A & Trasande L. (2018). Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine-Disrupting Chemicals on Child Neurodevelopment. Front Endocrinol (Lausanne) , 9, 204. PMID: 29760680 DOI.

"Endocrine-disrupting chemicals (EDCs) are natural and synthetic substances with ubiquitous exposure in children and adults including pregnant women. EDCs interfere, temporarily or permanently, with hormonal signaling pathways in the endocrine system by binding to hormone receptors and modifying gene expression."

Human stem cell pancreas implants

Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R & Anderson DG. (2016). Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. , 22, 306-11. PMID: 26808346 DOI.

Implanted in the intraperitoneal space of mice treated to chemically induce type 1 diabetes. Implants induced glycemic correction without any immunosuppression until their removal at 174 d after implantation. Human C-peptide concentrations and in vivo glucose responsiveness demonstrated therapeutically relevant glycemic control and retrieved implants contained viable insulin-producing cells.

Links: stem cells | pancreas
Menstrual cycle
Oral Contraceptives A recent 2016 Danish study births from Danish registries between 1997 and 2011 identified that:

Charlton BM, Mølgaard-Nielsen D, Svanström H, Wohlfahrt J, Pasternak B & Melbye M. (2016). Maternal use of oral contraceptives and risk of birth defects in Denmark: prospective, nationwide cohort study. BMJ , 352, h6712. PMID: 26738512

Links: menstrual cycle | drugs
Ernest Henry Starling (1866-1927)
Ernest Henry Starling (1866-1927)

Interested in hormone history?

Listen ABC Radio Ockham's Razor 2005-07-31 Centenary of the word "hormone" (6.2 Mb mp3) Centenary of the word 'hormone', Sydney medical scientist and writer Dr John Carmody commemorates the centenary of the entry of the word 'hormone' into the English language.

<html5media>File:Audio - centenary of hormone.mp3</html5media>

Lecture Objectives

  • Understanding of hormone types
  • Understanding of endocrine gland development
  • Understanding of endocrine developmental functions
  • Brief understanding of endocrine abnormalities
Lecture Archive  
2018 PDF | 2017 | 2017 PDF | 2016 | printable version | 2015 Lecture | 2014 Lecture | 2013 Lecture | 2012 Lecture | Endocrine System Development | BGD Lecture - Endocrine Histology | Practical - Virtual Slides
Logo.png Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved April 23, 2024, from
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
Previous Lecture Audio - These are a live unedited recording from the endocrine development lecture and may contain errors in either descriptions or content. This 2012 lecture was recorded locally due to a problem with the iLecture system. These recordings are for University level students and may not be suitable for young students. For educational purposes only. Dr Mark Hill Monday 22rd May 2012 9am Clancy

Links: Medicine Audio
Endocrinology - An Integrated Approach.png
Embryology textbooks do not have a specific chapter for endocrine system, read the head and neck and renal chapters. This general endocrine online textbook shown below should also be helpful.
Endocrinology Textbook - Chapter Titles  
Nussey S. and Whitehead S. Endocrinology: An Integrated Approach (2001) Oxford: BIOS Scientific Publishers; ISBN-10: 1-85996-252-1.

Full Table of Contents

Larsen's human embryology 5th ed.jpg
Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.

  UNSW students have full access to this textbook edition through UNSW Library subscription (with student Zpass log-in). Note that most embryology textbooks do no have specific chapter for endocrine development and this information is often found in other chapters (neural, renal, head, genital).

Larsen's Human Embryology (5th edn) 
Larsen's human embryology 5th ed.jpg
UNSW students have full access to this textbook edition through UNSW Library subscription (with student Zpass log-in).

APA Citation: Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.

Links: PermaLink | UNSW Embryology Textbooks | Embryology Textbooks | UNSW Library
  1. Gametogenesis, Fertilization, and First Week
  2. Second Week: Becoming Bilaminar and Fully Implanting
  3. Third Week: Becoming Trilaminar and Establishing Body Axes
  4. Fourth Week: Forming the Embryo
  5. Principles and Mechanisms of Morphogenesis and Dysmorphogenesis
  6. Fetal Development and the Fetus as Patient
  7. Development of the Skin and Its Derivatives
  8. Development of the Musculoskeletal System
  9. Development of the Central Nervous System
  10. Development of the Peripheral Nervous System
  11. Development of the Respiratory System and Body Cavities
  12. Development of the Heart
  13. Development of the Vasculature
  14. Development of the Gastrointestinal Tract
  15. Development of the Urinary System
  16. Development of the Reproductive System
  17. Development of the Pharyngeal Apparatus and Face
  18. Development of the Ears
  19. Development of the Eyes
  20. Development of the Limbs
The Developing Human: Clinically Oriented Embryology (10th edn) 
The Developing Human, 10th edn.jpg

UNSW Students have online access to the current 10th edn. through the UNSW Library subscription (with student Zpass log-in).

APA Citation: Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders.

Links: PermaLink | UNSW Embryology Textbooks | Embryology Textbooks | UNSW Library
  1. Introduction to the Developing Human
  2. First Week of Human Development
  3. Second Week of Human Development
  4. Third Week of Human Development
  5. Fourth to Eighth Weeks of Human Development
  6. Fetal Period
  7. Placenta and Fetal Membranes
  8. Body Cavities and Diaphragm
  9. Pharyngeal Apparatus, Face, and Neck
  10. Respiratory System
  11. Alimentary System
  12. Urogenital System
  13. Cardiovascular System
  14. Skeletal System
  15. Muscular System
  16. Development of Limbs
  17. Nervous System
  18. Development of Eyes and Ears
  19. Integumentary System
  20. Human Birth Defects
  21. Common Signaling Pathways Used During Development
  22. Appendix : Discussion of Clinically Oriented Problems

Se also - De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Tal R, Taylor HS, Burney RO, Mooney SB & Giudice LC. (2000). Endocrinology of Pregnancy. , , . PMID: 25905197

Endocrine Origins

  • Epithelia - (ectoderm) covering embryo, (endoderm) lining gastrointestinal tract, (mesoderm) lining coelomic cavity
  • Mesenchyme - (mesoderm) contribution, connective tissue, blood vessels


Hormone Types

Amino acid derivatives noradrenaline (norepinephrine), adrenalin (epinepherine) , thyroid hormone
Proteins, peptides thyroid stimulating hormone, leutenising hormone, follicle stimulating hormone
Steroids (from cholesterol) androgens, glucocorticoids, mineralocorticoids
Signaling Pathways  
Steroid biosynthesis pathway Steroid hormone receptor signaling
Steroid biosynthesis pathway Steroid hormone receptor signaling[1]
G-protein coupled receptors.jpg G-protein coupled membrane receptors
  • Adrenergic signalling (α and β receptors, with several subtypes)
  • Thyroid stimulating hormone (TSH), leutenising hormone (LH), follicle stimulating hormone (FSH) signalling

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

  • Cell surface receptors - modified amino acids, peptides, proteins
  • Cytoplasmic/Nuclear Receptors - steroids

Pineal Gland

Keith1902 fig167.jpg Pineal Development
  • Neuroectoderm - prosenecephalon then diencephalon (evagination of neuroepithelium located at roof of the third ventricle)
  • caudal roof, median diverticulum, epiphysis
  • Initially a hollow diverticulum, cell proliferation to solid, pinealocytes (neuroglia), cone-shaped gland innervated by epithalamus
Adult pineal body Pineal gland position
Adult pineal body Pineal gland position
  • part of epithalamus - neurons, glia and pinealocytes
  • pinealocytes secrete melatonin - cyclic nature of activity, melatonin lowest during daylight
  • maternal melatonin crosses the placental barrier
  • inhibit hypothalamic secretion of GnRH until puberty, pineal gland then rapidly regresses.
  • other activities - possibly gamete maturation, antioxidant effect, protect neurons?
Pineal histology 001.jpg
Fetal pineal gland 01.jpg Fetal Pineal Anatomy[2]
  • Human fetus (3.5 month) superior (dorsal) view diencephalic-mesencephalic area.
  • Third ventricle (3 ventr) without pial covering is seen to the right.
  • Pineal gland is a small protuberance (arrow) and merging via the broad stalk with the habenula (Ha). Superior colliculus (Sup col.)

Links: pineal | Endocrinology


Adult hypothalamus

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

Hypothalamic Hormones  
Adult Hypothalamic Hormones
Secreted hormone Abbreviation Produced by Effect
Thyrotropin-releasing hormone
(Prolactin-releasing hormone)
TRH, TRF, or PRH Parvocellular neurosecretory neurons thyroid-stimulating hormone (TSH) release from anterior pituitary (primarily)
Stimulate prolactin release from anterior pituitary
(Prolactin-inhibiting hormone)
DA or PIH Dopamine neurons of the arcuate nucleus Inhibit prolactin release from anterior pituitary
Growth hormone-releasing hormone GHRH Neuroendocrine neurons of the Arcuate nucleus Growth hormone (GH) release from anterior pituitary
(growth hormone-inhibiting hormone)
SS, GHIH, or SRIF Neuroendocrine cells of the Periventricular nucleus Growth hormone (GH) release from anterior pituitary
Inhibit Thyroid-stimulating hormone|thyroid-stimulating hormone (TSH) release from anterior pituitary
Gonadotropin-releasing hormone GnRH or LHRH Neuroendocrine cells of the Preoptic area follicle-stimulating hormone (FSH) release from anterior pituitary
Stimulate Luteinizing hormone|luteinizing hormone (LH) release from anterior pituitary
Corticotropin-releasing hormone CRH or CRF Parvocellular neurosecretory neurons adrenocorticotropic hormone (ACTH) release from anterior pituitary
Oxytocin Magnocellular neurosecretory cells Lactation (letdown reflex)
(antidiuretic hormone)
ADH or AVP Magnocellular neurosecretory neurons Increases water permeability in the distal convoluted tubule and collecting duct of nephrons, thus promoting water reabsorption and increasing blood volume
Melanin-concentrating hormone MCH tuberal lateral nucleus (lateral hypothalamic area) Neuropeptide with appetite stimulant (orexigenic) and sleep-promoting activities by projecting to a variety of brain areas.
  Links: hypothalamus‎

Hypothalamus Development

  • Neuroectoderm - prosenecephalon then diencephalon
  • ventro-lateral wall intermediate zone proliferation
  • Mamillary bodies - form pea-sized swellings ventral wall of hypothalamus
Stage 13 image 061.jpg Stage 22 image 055.jpg
Diencephalon region, shown by optic stalk
(Stage 13)
Late embryonic hypothalamus
(Stage 22)

Links: hypothalamus‎


Adult pituitary
Turkish saddle (17th century)
The pituitary (hypophysis) sits anatomically within the sella turcica, a space within the sphenoid bone.

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

Keith1902 fig015a.jpg Pituitary rabbit development.jpg
Pituitary development animation.gif Blue - neural tube ectoderm

Red - surface ectoderm

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


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


  • Infundibulum – median eminence, infundibulum, pars nervosa

Embryonic and fetal pituitary.jpg
Stage 22 image 220.jpg

Pituitary Timeline

Early Fetal (week 12)
  • 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 8 - basophilic staining cells appear
  • Week 9 - acidophilic staining cells appear
  • Week 10 - growth hormone and ACTH detectable
  • Week 16 - adenohypophysis fully differentiated and TSH increases to peak at 22 weeks
  • Week 20 to 24 - growth hormone levels peak, then decline
  • Birth - second TSH surge and decreases postnatally

Links: pituitary | Embryo Images - Pituitary | Endocrinology


Hypothalamus - Pituitary - Thyroid Axis
  • Maternal thyroid hormone - required for early stages of brain development
  • Fetal thyroid - begins function from week10, (GA week 12) required for neural development, stimulates metabolism (protein, carbohydrate, lipid), reduced/absence = cretinism (see abnormalities)

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

Thyroid Development

Stage 13 and Stage 22 thyroid development foramen caecum thyroid development
  • 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 caecum of tongue.
  • 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.
  • Week 16 - 18 - (GA 18-20 weeks) fully functional
Links: Box 3.21 Embryology of the thyroid and parathyroid glands

Fetal Thyroid Hormone

  • Initial secreted biologically inactivated by modification
    • serum thyroid hormone levels are relatively low and tissue concentration of thyroid hormone is modified by iodothyronine deiodinases
  • Iodine deficiency - during this period, leads to neurological defects (cretinism)
  • Late fetal secretion - develops brown fat
  • Birth - TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels
  • Post-natal - TH required for bone development

Maternal TH - iodine/thyroid status can affect development.

  • recent studies show that both high and low maternal thyroid hormone impact on neural development (PMID 26497402)
Links: thyroid | Endocrinology |


  • 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 adult

Adult Parathyroid

Parathyroid Development

  • 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
  • parathyroid hormone - (PTH, parathormone or parathyrin)
Pharyngeal pouches

Pharyngeal pouches

Links: parathyroid | Endocrinology


  • 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
  • third pharyngeal pouch - transient bilateral endodermal structures that generate both the thymus and parathyroid glands (some species also fourth pharyngeal pouch)
  • Thymic primordia - surrounded by neural crest mesenchyme, epithelia/mesenchyme interaction
  • Week 7 (Carnegie stage 18-19) thymic component migrates ventrally
  • Week 8 (CS20-21) differentiation of the cortical and medullary thymic epithelial cells (TEC).

Fetal Thymus

Links: thymus


  • 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 structure

Pancreas adult

Pancreas Development

  • 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
Pancreatic buds and duct developing Stage 22 pancreas
Pancreatic buds and duct developing Pancreas week 8 (Stage 22)
  • Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds See Figure 2.32
  • 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
Pancreas histology 104.jpg
Arterial blood (from splenic, hepatic and superior mesenteric arteries) enters the core of each islet and capillaries then drain outwardly to the periphery where venous blood drains into the splenic and superior mesenteric veins.

Histology image shows blood vessels injected with ink.

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: [[Pancreas}} | Gastrointestinal Tract - Pancreas Development | Endocrinology


Fetal adrenal gland (Week 10, GA week 12
  • Richly vascularized - arterioles passing through cortex, capillaries from cortex to medulla, portal-like circulation
  • Fetal Cortex - produces a steroid precursor (DHEAS), converted by liver and then 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

Adrenal medulla.jpg
  • Week 6 - fetal cortex, from mesothelium adjacent to dorsal mesentery; Medulla, neural crest cells from adjacent sympathetic ganglia
  • Fetal Adrenals - fetal cortex later replaced by adult cortex
  • 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 norepinephrine (noradrenaline) 20%
Adrenal medulla.jpg
 ‎‎Adrenal Medulla
Page | Play

Links: Endocrine - Adrenal Development | Endocrinology - Adrenal Cortex Development | Endocrinology


HPG female axis.jpg

Adult Hypothalamus - Pituitary - Gonad (female)

HPG male axis.jpg

Adult Hypothalamus - Pituitary - Gonad (male)

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

Gonad Development

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


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


  • 8 Weeks - mesenchyme, interstitial cells (of Leydig) secrete testosterone, androstenedione.
  • 8 to 12 Weeks - hCG stimulates testosterone production.
  • Sustentacular (Sertoli) cells - produce anti-mullerian hormone (AMH) to puberty.
    • AMH - anti-Müllerian hormone (Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS)).

Male testosterone and AMH level graph.jpg


Infant Ovary
  • X chromosome genes regulate ovary development
  • Hormone levels increase at puberty with follicle development.

I will cover this topic in detail again in sexual differentiation lecture/practical.

Links: Endocrine - Gonad Development | Endocrinology


Model male second trimester androsterone synthesis
Alternate androgen synthesis pathway[3]
The corpus luteum provides initial support, when it degenerates in the embryonic period, placental estrogen and progesterone production increases exponentially to term.
  • progesterone and estrogens - support maternal endometrium
  • 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)
  • 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)
    • in Males - an alternate androgen synthesis pathway
Placental Estrogen?  
Maternal late pregnancy estriol increases due to:[4]
  1. fetal adrenal gland production of DHEAS
  2. fetal liver conversion to 16α-OH-DHEAS
  3. placenta sulphate removal to allow aromatization to estriol.
  • Uterus - stimulates growth of the myometrium, antagonizes the myometrial-suppressing activity of progesterone.
  • Mammary Gland - stimulates mammary gland ductal and alveolar growth.
  • Fetal Ovary - stimulates development of female fetal ovary.[5]
Links: endocrine placenta
Trophoblast hCG function

Trophoblast hCG function

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).


NIH Genes & Disease Glands and Hormones


  • hypoplasia - associated with retinal disease.
  • tumours - in children are associated with abnormal puberty development.


  • craniopharyngeal canal - Rathke's pouch abnormality, from the anterior part of the fossa hypophyseos of the sphenoid bone to the under surface of the skull.
  • pituitary tumours (adenomas) - several abnormalities associated with abnormal levels of the hormonal output of the pituitary.
    • Growth hormone (GH) adenomas - benign pituitary tumors lead to chronic high GH output levels, that may lead to acromegaly.
  • Cushing's disease - caused either by a pituitary adenoma produces excess adrenocorticotropic hormone (ACTH, corticotropin) or due to ectopic tumors secreting ACTH or corticotropin-releasing hormone (CRH).


Thyroid pyramidal lobe
Thyroid uptake scans
  • Pyramidal lobe - from isthmus (50% of people) attached to hyoid bone distal end of thryoglossal duct.
  • Congenital hypothyroidism - approximately 1 in 3000 births, associated with neurological abnormalities.
  • Lingual thyroid gland - failure of thyroid descent.
  • Thyroglossal cyst - persistance of thyroglossal duct. Image - thyroglossal duct
  • Thyroglossal fistula - partial degeneration of the thyroglossal duct.
  • Abnormal development of the thyroid - incomplete or excessive descent.
  • Childhood hypothyroidism delays ossification and bone mineralization.

Iodine Deficiency

  • A teaspoon of iodine, total lifetime requirement, cannot be stored for long periods by our body, tiny amounts are needed regularly
  • Areas of endemic iodine deficiency, where soil and therefore crops and grazing animals do not provide sufficient dietary iodine to the populace
  • food fortification and supplementation - Iodized salt programs and iodized oil supplements are the most common tools in fight against IDD


  • Usually four glands are present (2 on each side), but three to six glands have been found in human.
  • Can have displaced parathyroid development with thymus.
  • Lower parathyroid glands arise from the third pharyngeal pouch and descend with the thymus. Variable descent can lead to a range of adult locations, from just beneath the mandible to the anterior mediastinum.


  • Type 1 Diabetes - juvenile onset diabetes, more severe form of illness, increases risk of blindness, heart disease, kidney failure, neurological disease, T-lymphocyte-dependent autoimmune disease, infiltration and destruction of the islets of Langerhans, Approx 16 million Americans
  • Type 2 Diabetes - loosely defined as "adult onset" diabetes, becoming more common cases of type 2 diabetes seen in younger people
  • Risk of developing diabetes - environmental factors (food intake and exercise play an important role, either overweight or obese), Inherited factors (genes involved remain poorly defined)


  • Congenital Adrenal Hyperplasia (CAH) - family of inherited disorders of adrenal steroidogenesis enzymes which impairs cortisol production by the adrenal cortex. Androgen excess leads newborn females with external genital ambiguity and postnatal progressive virilization in both sexes.
    • 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.
  • Pheochromocytomas (PCC) - Catecholamine-producing (neuro)endocrine tumor located in the adrenal medulla. Similar catecholamine-producing tumors outside the adrenal gland are called paragangliomas (PGL).

Endocrine Disruptors


Exogenous chemicals that interfere with the function of hormones. There are 3 main mechanisms: mimic, block or interfere.

Mimic - effects of natural hormones by binding receptors

  • Diethylstilbestrol - (DES or diethylstilbetrol) a drug prescribed to women from 1938-1971 to prevent miscarriage in high-risk pregnancies. Acts as a potent estrogen (mimics natural hormone) and therefore a potential endocrine disruptor. Female fetus, increased risk abnormal reproductive tract and cancer. Male fetus, abnormal genitalia. Banned by USA FDA in 1979 as a teratogen, previously used as livestock growth promoter.

Block - binding of a hormone to receptor or hormone synthesis

  • Finasteride - chemical used to prevent male pattern baldness and enlargement of prostate glands. An anti-androgen (blocks synthesis of dihydrotestosterone) and therefore a potential endocrine disruptor, exposed pregnant women can impact on male fetus genetial development.
  • Vinclozolin - a dicarboximide fungicide, perinatal exposure in rats inhibits morphological sex differentiation. In adult rats, shown to cause gonad tumours (Leydig cell) and atrophy. Chemical has androgen-antagonist (antiandrogenic) activity, metabolies compete with natural androgen

Interfere - with hormone transport or elimination

  • Polychlorinated biphenyl pollutants - (PCBs) Rats exposed to PCBs have low levels of thyroid hormone. Compete for binding sites of thyroid hormone transport protein. Without being bound to this protein, thyroid hormones are excreted from the body (McKinney et al. 1985; Morse et al. 1996)

Links: Endocrine Disruptors


  1. Griekspoor A, Zwart W, Neefjes J & Michalides R. (2007). Visualizing the action of steroid hormone receptors in living cells. Nucl Recept Signal , 5, e003. PMID: 17464358 DOI.
  2. Møller M, Phansuwan-Pujito P & Badiu C. (2014). Neuropeptide Y in the adult and fetal human pineal gland. Biomed Res Int , 2014, 868567. PMID: 24757681 DOI.
  3. O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, Savchuk I, Monteiro A, Soffientini U, Johnston ZC, Bellingham M, Hough D, Walker N, Filis P & Fowler PA. (2019). Alternative (backdoor) androgen production and masculinization in the human fetus. PLoS Biol. , 17, e3000002. PMID: 30763313 DOI.
  4. Raeside JI. (2017). A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine. Yale J Biol Med , 90, 449-461. PMID: 28955183
  5. Albrecht ED & Pepe GJ. (2010). Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy. Int. J. Dev. Biol. , 54, 397-408. PMID: 19876841 DOI.
  • Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. London:Taylor & Francis; c2001 Major hormone types
  • Genes and Disease, Bethesda (MD): National Library of Medicine (US), NCBI Glands and Hormones




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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Endocrine Development Interactive Component

Attempt the Quiz - Endocrine Development  

Here are a few simple Quiz questions that relate to Endocrine development and abnormalities from the lecture. Some questions may require some additional research.

1 Which of the following originates from surface ectoderm?

  adrenal cortex

2 Which of the following arise from the endoderm?

  the pancreatic acinous cells
  pancreatic duct cells
  all of the above

3 The neural crest cells from the sympathetic ganglia migrate to form the:

  pars nervosa of the pituitary gland
  medulla of the adrenal gland
  follicular cells of the thyroid gland
  inferior parathyroids
  pars intermedia of the pituitary gland

4 During fetal life the parathyroid glands:

  contain oxyphil cells that degenerate before birth
  contain parafollicular cells that secrete hormones to regulate
  develop in situ from cervical somites
  migrate cephalically from the thymus to reach the cervical region

5 The parafollicular cells of the thyroid originate from the:

  neural crest

6 Congenital suprarenal hyperplasia:

  causes an increase in adrenal cortical hormones
  inhibits release of ACTH by the pituitary
  causes masculinisation of external genitalia in female fetuses
  may lead to adrenal cortical insufficiency, although there is an
  overproduction of adrenal cortical hormones

7 Pituitary hypoplasia may result in:

  maldevelopment of the adrenal cortex
  maldevelopment of the thyroid gland
  hypoplastic gonads
  all of the above

8 In congenital adrenal hypoplasia due to unresponsiveness to ACTH:

  the aldosterone levels are normal
  the skin is hyperpigmented
  the ACTH level is increased
  all of the above are correct

9 Which of the following is the most correct statement concerning the thyroid pyramidal lobe:

  is a failure of thyroid descent
  is a persistance of thyroglossal duct
  occurs in about 1 in 3000 births
  is associated with neurological abnormalities
  occurs in about 50% of people

10 Endocrine disruptors are exogenous chemicals that interfere with the function of hormones. Which of the following best describes the endocrine action of "Diethylstilbestrol (DES)"?

  Mimics to replicate the effects of natural hormones by binding receptors
  Blocks to inhibit the binding of a hormone to receptor or hormone synthesis
  Interferes to compromise with the hormone transport or elimination

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