2010 Lecture 19

From Embryology

Introduction

Head and Neck
Pituitary

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 (Hyothalamus-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.

2013: Link to current lecture

Lecture Objectives

  • Understanding of hormone types
  • Understanding of endocrine gland development
  • Understanding of endocrine developmental functions
  • Brief understanding of endocrine abnormalities

Textbooks

In general, not dealt with as a system in many textbooks, so various chapters: nervous system, head, gastrointestinal tract, reproductive organs, etc.

  • 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 - 2008 | Medicine Lecture - Endocrine Development
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 | 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 | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1937 Pineal | 1938 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal
| original Endocrine page

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

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


MH - 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.

Endocrine Origins

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

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

Embryonic and fetal pituitary.jpg

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
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

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

Adrenal medulla.jpg
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%

Media:Adrenal_medulla.mov

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)

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.
  • 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

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)

References

  1. <pubmed>17464358</pubmed>| PMC1853070 | Nucl Recept Signal.

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Histology

Adult

Embryonic

Terms

adrenocorticotropin - (ACTH or corticotropin) anterior pituitary, peptide hormone

antidiuretic hormone - (ADH) hypothalamus, peptide hormone

atrial natriuretic factor - (ANP) heart, , peptide hormone

calcitonin - (CT) C cells of thyroid, peptide hormone

follicle stimulating hormone - (FSH) pituitary, protein hormone

growth hormone - (GH) pituitary, peptide hormone

human chorionic gonadotropin - (hCG) pancreas 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

lutenizing hormone - (LH) pituitary, protein hormone

melaocyte stimulating hormone - (MSH) pituitary, peptide hormone

prolactin - (PRL) pituitary, peptide hormone

parathyroid hormone - (PTH) parathyroid, peptide hormone

thyroid hormone - (TH) thyroid,amino acid derivative

thyroid stimulating hormone - (TSH) pituitary, protein hormone

Glossary Links

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

Course Content 2010

Embryology Introduction | Cell Division/Fertilization | Lab 1 | Week 1&2 Development | Week 3 Development | Lab 2 | Mesoderm Development | Ectoderm, Early Neural, Neural Crest | Lab 3 | Early Vascular Development | Placenta | Lab 4 | Endoderm, Early Gastrointestinal | Respiratory Development | Lab 5 | Head Development | Neural Crest Development | Lab 6 | Musculoskeletal Development | Limb Development | Lab 7 | Kidney | Genital | Lab 8 | Sensory | Stem Cells | Stem Cells | Endocrine | Lab 10 | Late Vascular Development | Integumentary | Lab 11 | Birth, Postnatal | Revision | Lab 12 | Lecture Audio | Course Timetable


Cite this page: Hill, M.A. (2019, January 20) Embryology 2010 Lecture 19. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2010_Lecture_19

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G