Lecture - Endocrine Development

From Embryology

Introduction

Hypothalamus endocrine system
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 “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 (Hypothalamus-Pituitary-Adrenal) and HPG (Hypothalamus-Pituitary-Gonad). 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. Importantly, fetal endocrine development is required for normal fetal growth and differentiation.


2016 Lecture Video Recording  
This 2016 lecture video recording is similar in content to the current 2017 online lecture.

Click to play new window - 2016 Lecture Video (48 MB)

Lecture Objectives

  • Understanding of hormone types
  • Understanding of endocrine gland development
  • Understanding of endocrine developmental functions


Endocrine in the News  
Human stem cell pancreas implants


"Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice."

PMID 26808346 | Nat Med.

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 | Endocrine - Pancreas Development
Menstrual cycle
Oral Contraceptives A recent 2016 Danish study births from Danish registries between 1997 and 2011 identified that:


"Oral contraceptive exposure just before or during pregnancy does not appear to be associated with an increased risk of major birth defects."

PMID 26738512 | BMJ


Links: Menstrual Cycle | Abnormal Development
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.

Lecture Resources

Movies  
Adrenal medulla.jpg
 ‎‎Adrenal Medulla
Page | Play
Aschheim-Zondek Test 1928.jpg
 ‎‎Pregnancy Test
Page | Play
Human fetal adrenal GA32.jpg
 ‎‎Adrenal GA32
Page | Play
Stage13-GIT-icon.jpg
 ‎‎GIT Stage 13
Page | Play
Stage22-CNS-icon.jpg
 ‎‎Urogenital
Page | Play
References  
UNSW Embryology logo
Hill, M.A. (2017). UNSW Embryology (17th ed.) Retrieved December 18, 2017, from https://embryology.med.unsw.edu.au
Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 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 Hypophyseal fossa | 1935 Hypophysis | 1937 Pineal | 1938 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal
The endocrine "System" is not covered by a specific chapter in the embryology textbooks and you will need to look for related chapters on the development of individual components (some selected examples are listed below). Use the listed Endocrinology textbook for detained descriptions of function.
Endocrinology - An Integrated Approach.png

Nussey, S. and Whitehead, S. (2001). Endocrinology - An Integrated Approach. UK Oxford: BIOS Scientific Publishers. ISBN-10: 1-85996-252-1

Detailed Table of Contents | Bookshelf Link
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: 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: 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

Endocrine Origins

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

Hormones

Steroid hormone receptor signaling[1]

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

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


Interested in hormone history? Listen ABC Radio Ockham's Razor 2005-07-31 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.

Pineal Gland

Keith1902 fig167.jpg 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 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: Endocrine - Pineal Development | Endocrinology

Hypothalamus

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

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: Endocrine - Hypothalamus Development

Pituitary

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

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

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: Endocrine - Pituitary Development | Embryo Images - Pituitary | Endocrinology

Thyroid

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: Endocrine - Thyroid Development | Endocrinology |

Parathyroid

  • 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: Endocrine - Parathyroid Development | Endocrinology

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
Gray1178.jpg

Fetal Thymus

Links: Endocrine - Thymus Development

Pancreas

  • 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
Islet
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: Endocrine - Pancreas Development | Gastrointestinal Tract - Pancreas Development | Endocrinology

Adrenal

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 (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

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 norepinepherine (noradrenaline* 20%
Adrenal medulla.jpg
 ‎‎Adrenal Medulla
Page | Play


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

Gonad

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

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 (required for male genital development)
  • 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

Ovary

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


I covered this topic in detail in sexual differentiation lecture/practical.


Links: Endocrine - Gonad Development | Endocrinology

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).

Abnormalities

NIH Genes & Disease Chapter 41 - Glands and Hormones

Pineal

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

Pituitary

  • 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

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

Parathyroid

  • 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.

Pancreas

  • 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)

Adrenal

  • 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

Diethylstilbestrol

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:

References

  1. Alexander Griekspoor, Wilbert Zwart, Jacques Neefjes, Rob Michalides Visualizing the action of steroid hormone receptors in living cells. Nucl Recept Signal: 2007, 5;e003 PubMed 17464358 | PMC1853070 | Nucl Recept Signal.
  2. Morten Møller, Pansiri Phansuwan-Pujito, Corin Badiu Neuropeptide Y in the adult and fetal human pineal gland. Biomed Res Int: 2014, 2014;868567 PubMed 24757681 | PMC3976832 | Biomed Res Int.

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Terms

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 2017 ANAT2341 - Timetable | Course Outline | Group Projects | Moodle | Tutorial 1 | Tutorial 2 | Tutorial 3

Labs: 1 Fertility and IVF | 2 ES Cells to Genome Editing | 3 Preimplantation and Early Implantation | 4 Reproductive Technology Revolution | 5 Cardiac and Vascular Development | 6 CRISPR-Cas9 | 7 Somitogenesis and Vertebral Malformation | 8 Organogenesis | 9 Genetic Disorders | 10 Melanocytes | 11 Stem Cells | 12 Group

Lectures: 1 Introduction | 2 Fertilization | 3 Week 1/2 | 4 Week 3 | 5 Ectoderm | 6 Placenta | 7 Mesoderm | 8 Endoderm | 9 Research Technology | 10 Cardiovascular | 11 Respiratory | 12 Neural crest | 13 Head | 14 Musculoskeletal | 15 Limb | 16 Renal | 17 Genital | 18 Endocrine | 19 Sensory | 20 Fetal | 21 Integumentary | 22 Birth | 23 Stem cells | 24 Revision

 Student Projects: 1 Cortex | 2 Kidney | 3 Heart | 4 Eye | 5 Lung | 6 Cerebellum