BGD Lecture - Endocrine Development
|Embryology - 22 Sep 2017 Expand to Translate|
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- 1 Introduction
- 2 Endocrine Origins
- 3 Hormones
- 4 Pineal Gland
- 5 Hypothalamus
- 6 Pituitary
- 7 Thyroid
- 8 Parathyroid
- 9 Thymus
- 10 Pancreas
- 11 Adrenal
- 12 Gonad
- 13 Placenta
- 14 Other Endocrine
- 15 Endocrine Functional Changes
- 16 Abnormalities
- 17 References
- 18 Histology
- 19 Terms
- 20 Textbooks
- 21 Glossary Links
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.
|Endocrine in the News|
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.
PMID 26738512 | BMJ
|BGD Lecture Links: 2017 PDF ||
- Epithelia - (ectoderm) covering embryo, (endoderm) lining gastrointestinal tract, (mesoderm) lining coelomic cavity
- Mesenchyme - (mesoderm) contribution, connective tissue, blood vessels
- Amino acid derivatives - noradrenaline (norepinephrine), adrenalin (epinepherine) , thyroid hormone
- Proteins, peptides - thyroid stimulating hormone, leutenising hormone, follicle stimulating hormone
- Steroids - androgens, glucocorticoids, mineralocorticoids
|Steroid biosynthesis pathway||Steroid hormone receptor signaling|
| G-protein coupled membrane receptors
- Autocrine - acts on self (extracellular fluid)
- Paracrine - acts locally (extracellular fluid)
- Endocrine - acts by secretion into blood stream (endocrine organs are richly vascularized)
- Cell surface receptors - modified amino acids, peptides, proteins
- Cytoplasmic/Nuclear Receptors - steroids
|Adult pineal body||Pineal gland position|
|Fetal Pineal Anatomy
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
- Neuroectoderm - prosenecephalon then diencephalon
- ventro-lateral wall intermediate zone proliferation
- Mamillary bodies - form pea-sized swellings ventral wall of hypothalamus
|Diencephalon region, shown by optic stalk
|Late embryonic hypothalamus|
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
| 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
- 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
- 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 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.
- 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
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)
Principal cells cords of cells
- 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
- 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||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
Histology image shows blood vessels injected with ink.
- 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
- 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
- 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
- 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
- Late Fetal Period - differentiates to form cortical zones
- Birth - zona glomerulosa, zona fasiculata present
- Year 3 - zona reticularis present
Adult Hypothalamus - Pituitary - Gonad (female)
Adult Hypothalamus - Pituitary - Gonad (male)
- 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)).
- X chromosome genes regulate ovary development
- Hormone levels increase at puberty with follicle development.
Trophoblast hCG function
- Atrial natriuretic peptide (ANP) - Increase Filtration rate / decrease Na+ reabsorption
- Endothelins - ET-1, ET-2, ET-3, Vasoconstriction / Increase NO
- Nitric oxide (NO) - Vasodilatation
- 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
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
- 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).
- 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.
- 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).
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
- 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.
- 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.
- 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
- Bookshelf endocrine | pineal gland | hypothalamus | pituitary gland | thyroid gland | parathyroid gland | thymus gland | endocrine pancreas | adrenal gland
- Pubmed endocrine development
- 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
- corticosteroid binding globulin - (CBG) binds and transports glucocorticoids in the plasma. Globin is synthesised in the liver.
- 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
| Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.
This textbook does not have a specific chapter on endocrine development (look at head development, neural development, neural crest development, genital development chapters). UNSW Library connection.
|Stephen Nussey, S. and Whitehead S. (2001) Endocrinology - An Integrated Approach London, UK Oxford: BIOS Scientific Publishers.|
| Hill, M.A. (2017). UNSW Embryology (17th ed.) Retrieved September 22, 2017, from https://embryology.med.unsw.edu.au
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Cite this page: Hill, M.A. 2017 Embryology BGD Lecture - Endocrine Development. Retrieved September 22, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/BGD_Lecture_-_Endocrine_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G