Endocrine System Development

Embryology - 1 Dec 2023        Expand to Translate
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Introduction

Human adrenal gland (Week 10)

Adult endocrine organs

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

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

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

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

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

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

Pineal

Hypothalamus

Pituitary

Thyroid

Thymus

Pancreas

Some Recent Findings

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

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References See also specific endocrine organ pages for more specific search options. Search term: Endocrine Development | Endocrine Embryology

Older papers
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Pituitary Gland Development review article looking at molecular mechanisms of development.

Textbooks

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

Endocrinology Textbook - Chapter Titles   Nussey S. and Whitehead S. Endocrinology: An Integrated Approach (2001) Oxford: BIOS Scientific Publishers; ISBN-10: 1-85996-252-1. Chapter 1. Principles of endocrinology Chapter 2. The endocrine pancreas Chapter 3. The thyroid gland Chapter 4. The adrenal gland Chapter 5. The parathyroid glands and vitamin D Chapter 6. The gonad Chapter 7. The pituitary gland Chapter 8. Cardiovascular and renal endocrinology Full Table of Contents

Endocrinology Textbook - Table of Contents   Endocrinology - An Integrated Approach Stephen Nussey and Saffron Whitehead. St. George's Hospital Medical School, London, UK Oxford: BIOS Scientific Publishers; 2001. ISBN-10: 1-85996-252-1 Principles of endocrinology Functions of hormones and their regulation Chemical signalling - endocrine, paracrine, autocrine and intracrine mechanisms Chemical classification of hormones and their synthesis Hormone synthesis Transport of hormones in the circulation and their half-lives Hormone receptors - cell surface Hormone receptors - intracellular Hormones and gene transcription Hormone receptor regulation Neuroendocrine interactions Hormones and the immune system Hormones, growth promotion and malignancy Genes, mutations and endocrine function Clinical evaluation of endocrine disorders The endocrine pancreas Glucose turnover Anabolic and catabolic phases of glucose metabolism Actions of insulin and glucagon Lipid metabolism - insulinopenia and diabetic ketosis Protein metabolism and the anabolic actions of insulin Definition and diagnosis of diabetes mellitus Etiology of type 1 DM Prevention of type 1 DM Structure, synthesis and metabolism of insulin and glucagon Anatomical features of pancreatic islets in relation to hormone secretion and its control Control of insulin and glucagon secretion Type 2 DM Causes of DM Genetic disorders of β-cell function Counter-regulatory hormones and DM Complications of DM Macrovascular circulatory changes Microvascular changes - diabetic retinopathy, nephropathy and neuropathy Diabetes and the neuropathic foot Diabetes and insulin resistance of pregnancy Development of the pancreas: effects of DM on organogenesis Treatment of DM - rationale and practical considerations Hypoglycemia Physiological responses to hypoglycemia and its treatment Hypoglycemia and insulinoma Hypoglycemia in infancy Disorders of the α, γ and PP cells of the islets Clinical case questions The thyroid gland Iodine intake Anatomical features of the thyroid gland Iodine trapping and thyroid function Synthesis of thyroid hormones Actions of thyroid hormones Control of thyroid hormone synthesis and secretion Hyperthyroidism — Graves' disease Surgical anatomy and embryology of the thyroid gland Primary hypothyroidism — Hashimoto's disease and myxedema Secondary hypothyroidism Hypothyroidism in infancy and childhood Thyroid hormone resistance Non-thyroid illness (‘sick euthyroid’ syndrome) Transport and metabolism of thyroid hormones Biochemical measurements of thyroid hormone status Thyroid growth Nodular thyroid disease Thyroid cancer Clinical case questions The adrenal gland Specificity of the biological effects of adrenal steroid hormones Cholesterol and steroid synthesis in the adrenal cortex Anatomical and functional zonation in the adrenal cortex Glucocorticoid receptors Actions of glucocorticoids and clinical features of Cushing's syndrome Adrenal cortical androgens Hypothalamic control of adrenocortical steroid synthesis - CRH and vasopressin Pituitary control of adrenocortical steroids - ACTH Feedback control of glucocorticoids Excess glucocorticoids: biochemical investigation of Cushing's syndrome Measurements of cortisol in blood, urine and saliva Dynamic tests of endocrine function Imaging the adrenal gland Treatment of Cushing's syndrome Nelson's syndrome Excess adrenal androgens - congenital adrenal hyperplasia (CAH) Deficiency of adrenocortical secretions - Addison's disease Aldosterone and the control of salt and water balance Transport and metabolism of adrenocortical steroids Selective mineralocorticoid excess and deficiency The adrenal medulla and pheochromocytoma Catecholamine synthesis and secretion Diagnosis and treatment of pheochromocytomas Clinical case questions The parathyroid glands and vitamin D Calcium and phosphate in serum and its measurement Intracellular calcium concentration Calcium and phosphate balance Hormonal control of serum Ca2+ and Pi concentrations Sources, metabolism and transport of vitamin D Classical actions of vitamin D on intestine and bone Parathyroid glands and PTH synthesis Control of PTH secretion Actions of PTH Hypercalcemia and primary hyperparathyroidism Hyperparathyroidism and multiple endocrine neoplasia (MEN) Hypercalcemia and vitamin D excess Hypercalcemia and malignancy Parathyroid hormone-related peptide (PTHrp) Treatment of hypercalcemia Mutations of the Ca2+ or PTH receptors Hypocalcemia and its treatment Pseudohypoparathyroidism Vitamin D deficiency Non-classical actions of vitamin D Vitamin D resistance and rickets Hormones and the skeleton Structure, formation and function of bone Osteoporosis Paget's disease (osteitis deformans) Calcitonin and calcitonin gene-related peptide Clinical case questions The gonad Genetic determination of sexual differentiation Sexual differentiation of the gonads and internal reproductive tracts Sexual differentiation of the external genitalia Control of steroid production in the fetal gonads Puberty GnRH and the control of gonadotrophin synthesis and secretion The gonadotrophins - LH and FSH - and their actions Endocrine changes in puberty Precocious sexual development Delayed puberty Premature adrenarche Acne, hair growth and hirsutism The breast - premature development, hypoplasia and gynecomastia Testicular function Control of testicular function Transport, metabolism and actions of androgens Spermatogenesis Erection and ejaculation Ovarian control and the menstrual cycle Transport, metabolism and actions of ovarian steroids The ovary - folliculogenesis and oogenesis Non-steroidal factors in the control of the hypothalamic-pituitary-gonadal axis Ovulation, menstruation and its problems Polycystic ovary syndrome (PCOS) Contraception Infertility Ovulation induction and assisted conception Ovarian failure, the menopause and andropause Hormonal replacement therapy (HRT) and selective estrogen receptor modulators (SERMS) Clinical case questions The pituitary gland Anatomical and functional connections of the hypothalamo-pituitary axis Embryology of the pituitary gland Craniopharyngioma Blood supply of the hypothalamo-pituitary axis Sheehan's syndrome Growth and somatotrophin deficiency Growth hormone - secretory patterns and control Actions of growth hormone and insulin-like growth factors GH replacement therapy GH excess - gigantism and acromegaly Pituitary adenomas - incidence and treatment Prolactinomas Prolactin and its control Circadian rhythms and the suprachiasmatic nucleus The pineal gland and melatonin Autonomic functions of the hypothalamus Obesity The neural lobe of the pituitary gland - AVP and oxytocin Clinical case questions Cardiovascular and renal endocrinology Endocrinology of heart failure Paracrine and autocrine regulation of blood pressure: the endocrinology of sepsis Hormones and blood cell production - erythropoietin Carcinoid Clinical case questions

• 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 - Lecture - Endocrine Development | 2010 | 2009 |
• The Endocrine System - An Overview (PDF)

Larsen's Human Embryology - UNSW Students

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). Chapter 9 Development of the Hypothalamus Chapter 9 Development of the Pineal Gland Chapter 9 Development of the Pituitary Chapter 14 Development of the Pancreas Chapter 15 Development of the Suprarenal Gland Chapter 16 Development of the Gonad Chapter 17 Development of the Thyroid

Objectives

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

Hormones

Steroid hormone receptor signaling

Hormone Types

Steroid biosynthesis pathway

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

Hormone Actions

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

Hormone Receptors

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

Interested in endocrine and hormone history? Listen to ABC Radio Ockham's Razor 2005-07-31 Centenary of the word "hormone" (File:Audio - centenary of hormone.mp3), by Sydney medical scientist (from SOMS) and writer Dr John Carmody commemorates the centenary of the entry of the word 'hormone' into the English language.

Links: Hormones

Endocrine Origins

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

Development Overview

See specific endocrine organ development.

Human Endocrine - Embryonic Timeline
Data based on data from O'Rahilly (1983). Pineal (Epiphysis) | Pituitary (Hypophysis) | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ (Suprarenal)
Stage 13 (week 4) Pituitary - basement membranes of the craniopharyngeal pouch and the brain are clearly in contact. Thymus‎ - Weller (1933) recognized already a thymic primordium "of considerable size" on the ventral part of the third pharyngeal pouch, whereas Norris (1938) considered this stage to be "preprimordial" Thyroid - median thyroid is now bilobed and is connected to the pharynx by a hollow pedicle. The telopharyngeal body has been regarded as a "lateral thyroid component" by some workers. Pancreas - ventral pancreas may perhaps be distinguishable.
Stage 14 (week 5) Pineal - a slight irregularity in the surface outline of the intact head corresponds to the future pineal body (O'Rahilly et al. 1982). Pituitary - craniopharyngeal pouch is prominent and the notochord appears to be inserted into its dorsal wall. The craniopharyngeal pouch has become elongated and blood vessels are beginning to grow in between the basement membranes of the pouch and brain. Thyroid - thyroid pedicle shows further elongation but is still connected to the epithelium of the pharynx. Right and left lobes and an isthmus may perhaps be presaged (ibid.). Parathyroids - "Parathyrogenic zones" are recognizable. The parathyroid 4 primordium has been illustrated at this stage by Weller (1933, Fig. 16). Thymus‎ - Weller's (1933) "thymus" (the third pharyngeal pouch) becomes elongated. Pancreas - ventral pancreas (which may perhaps be distinguishable as early as stage 13) appears as an evagination from the bile duct at stages 14 and 15. It is generally described as unpaired but, at least in some cases, may perhaps be bilobed or even multiple (Delmas 1939). Adrenal‎ Adrenal Cortex - A change in the characteristics of the cells of the coelomic epithelium appears between the mesogastrium and the lateral end of the mesonephros. Adrenal Medulla - paravertebral sympathetic ganglia increase in size as a result of cell division and the addition of nerve fibres from the rami communicantes. The ganglia contain three types of cells: MI, M2, and M3. The M3 cells are the" parasympathetic cells" of Zuckerkandl.
Stage 15 Pineal - pineal body is detectable in the roof of the diencephalon (Stadium I of Turkewitsch) Thyroid - thyroid primordium may be detached from the pharyngeal epithelium in some instances. "At about the time" when the thyroglossal duct "becomes broken it loses its lumen". Adrenal‎ Adrenal Cortex - primordium is first recognizable. A new type of cell (C1) from the coelomic epithelium is found in the subjacent mesenchyme. New cells (C2) appear in the medial wall of mesonephric glomeruli and begin to migrate into the suprarenal primordium. denies a mesonephric contribution to the suprarenal. Adrenal Medulla - all types of cells (M1, M2, and M3) increase in number. From stage 15 to stage 18, the suprarenal primordium is cigar-shaped and extends from segment T6 to segment L1, lateral to the aorta and mesogastrium.
Stage 16 (week 6) Pituitary - slight indication of the infundibular recess may be seen in some embryos. Pineal - cellular migration in an external direction occurs in the pineal body during stages 16 and 17 (Stadium 2 of Turkewitsch) Thymus - according to Norris (1938) , "not until the primordium of the parathyroid [3] has been outlined can the remaining portion of the third pouch be recognized, by exclusion, as the primordium of the endodermal thymus". Parathyroids - parathyrogenic zones are closely related to the third and fourth aortic arches at 9 mm unstaged embryo). Parathyroid 3 is identifiable on the anterior wall of the third pharyngeal pouch (Weller 1933, Fig. 17) and "does not arise from a dorsal lobule" of the pouch. The "sudden appearance of well-differentiated clear chief cells in the early primordia of the parathyroids" at 9 mm. Thyroid - has lost its continuity with the pharynx and it consists of two lobes, an isthmus, and a remnant of the pedicle. Adrenal‎ Adrenal Cortex - Another type of cell (C3) arises from the coelomic epithelium. Both C1 and C3 cells enter the suprarenal primordium. An "enormous immigration" of C2 cells occurs. Adrenal Medulla - cells of neural origin are migrating into the gland, separating the cortical cells into islands. Nerve fibres from the ganglia accompany the M1 and M3 cells. The M2 cells remain in the ganglia and become sympathetic ganglion cells. Pancreas - dorsal pancreas and the ventral pancreas are contiguous.
Stage 17 Pituitary - juxtacerebral wall of the craniopharyngeal pouch is the thicker. The lateral lobes (future infundibular, or tuberal, part) and the anterior chamber (Vorraum) are clearly visible.The infundibular recess displays a characteristically folded wall, namely the neurohypophysis. Thymus - connection of the thymus with the pharynx has been severed (Weller 1933). The thymus is intimately approximated to the cervical duct (ibid.) According to Norris (1937), both third and fourth pouches make contact with the ectoderm, although only the third "receives an increment from the ectoderm". Parathyroids -parathyroid 4 is attached to the lateral surface of what Weller (1933) termed the "lateral thyroid component" Thyroid. The lobes of the thyroid curve around the carotid arteries and are connected by a delicate isthmus. Lacunae "should not be confused with lumina of follicles". Adrenal‎ Adrenal Cortex - dorsal part of the whole suprarenal primordium is disorganized by the invasion of sympathetic nerves and cells, while the band of C2 cells and the coelomic epithelium remain intact (Crowder 1957). Adrenal Medulla - first neural migration is at its height. Growth of the para-aortic complex is extensive. The plexiform complex is derived from paravertebral sympathetic ganglia T6-12 and usually L 1. Included in it are the primordia of the suprarenal medulla and of the celiac, superior mesenteric, and renal plexuses. Nerve fibres and "paraganglion" (M3) cells enter. Pancreas - ventral pancreas has now fused with dorsal. Perhaps the ventral and dorsal ducts have begun to blend (Russu and Vaida 1959).
Stage 18 (week 7) Pineal - cellular migration in the pineal body forms a distinct "anterior lobe" in which follicles appear (Stadium 3 of Turkewitsch)) Thymus- thymus makes contact with the thyroid gland and contains a series of canals internally (Weller 1933). Thyroid - median thyroid is in contact with "lateral thyroid components"but others have maintained that the telopharyngeal body should not be regarded as a thyroid component (Bejdl and Politzer 1953). The lobes of the thyroid are "composed of series of continuously communicating solid annectent bars" this is "the earliest stage of the definitive thyroid". First differentiation occurs in Weller's (1933) "lateral thyroid component," which is beginning to "blend into uniformly constituted thyroid tissue". Weller (1933) illustrated (Fig. 11) a thyroid gland that still showed continuity between its pedicle and the epithelium of the pharynx. Adrenal‎ Adrenal Cortex - gland becomes reorganized. The C1, 2, and 3 cells form cords as sinusoids develop. Cells divide at or near the surface, where new cells are added.
Stage 19 Pituitary - the caudal part of the craniopharyngeal pouch is reduced to a closed epithelial stem. Epiphysis - the "anterior lobe" of the pineal body shows a characteristic step and wedge appearance (Stadium 4 of Turkewitsch)) Parathyroids - 3 become detached from the pharyngeal endoderm. Adrenal Cortex - C2 cells lie on the surface of the gland and form a "capsule". Adrenal Medulla - Sympathicoblasts penetrate the cortex at stages 19 and 20, and form scattered islets of medullary tissue throughout the cortex.
Stage 20 (week 8) Pituitary - the adenohypophysial epithelium adjacent to the neurohy- pophysis constitutes the beginning pars intermedia. The walls of the craniopharyngeal pouch bud into the mesenchyme. Thymus - the right and left components are in contact with each other but are "never completely fused" ). Thymic cortex appears (in stages 20-22) as a result, according to Norris (1938), of migration of and covering by "cells derived from the cervical sinus". Parathyroids - the parathyroid glands are attached to the lateral lobes of the thyroid (Weller 1933). Weller (1933, Fig. 23) showed parathyroid 3 still rostral to parathyroid 4 at 23 mm, whereas (presumably due to variation in the "descent" of the thymus) (Norris 1937, Fig. 4) showed parathyroid 3 rostral to, level with, and caudal to parathyroid 4 in embryos of 16-17 mm. Thyroid - the "annectent bars" of the thyroid are more compact then previously. The thyroid now exhibits its definitive external form.
Stage 21 Hypophysis - the pharyngeal stalk becomes fragmented. Adrenal‎ Adrenal Cortex - the cellular "capsule" becomes covered by a layer of fibrous tissue.
Stage 22 Parathyroids - Parathyroids 4 become detached from the pharyngeal endoderm. Adrenal‎ Adrenal Cortex - the C2 cells have changed and resemble fibrocytes.
Stage 23 Pituitary - adenohypophysis loss of the stalk and lobules of epithelium project into the mesodermal component of the gland, and oriented epithelial follicles are present (Streeter, 1951, plate 2). Abundant angioblasts and capillaries are found. Epiphysis - The pineal body has reached Stadium 5 of Turkewitsch Thymus - The cortex is well-developed, "true lobulation" has begun with the appearance of" fine superficial scallops," lymphocytes are present sparsely in the subcortical zone, and vessels are found within the thymus. Adrenal‎ Adrenal Cortex - It appears that C2 cells first enter the body of the gland at this stage. The pattern of the arterial supply is established. The cellular "capsule" is penetrated by arterial capillaries which join the sinusoids. Their points of entry give the surface of the gland an appearance of cobblestones. The zona glomerulosa is formed of CI and C3 cells. Cells from this zone and from the "capsule" migrate centrally into the cords. Adrenal Medulla - Nerve fibres and neuroblasts are first seen in the body of the gland. The paragangtion (M3) cells are beginning to multiply rapidly and, from 30 mm (stage 23) until birth, some are differentiating into chromaffin cells.

Links: Endocrine embryo table

Pineal Gland

Adult pineal body

Pineal gland position

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

Pineal Development

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

Links: Endocrine - Pineal Development

Hypothalamus

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

Hypothalamus Development

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

Links: Endocrine - Hypothalamus Development

Pituitary

Adult pituitary

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

Posterior pituitary hormones - Oxytocin, Arginine vasopressin

Pituitary Development

Pituitary rabbit development

Blue - neural tube ectoderm Red - surface ectoderm

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

Adenohypophysis

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

Neurohypophysis

• Infundibulum – median eminence, infundibulum, pars nervosa

Pituitary Timeline

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

Links: Endocrine - Pituitary Development | Embryo Images - Pituitary

Thyroid

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

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

Thyroid Development

Stage 13 and Stage 22 thyroid development

foramen caecum

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

Thyroid Timeline

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

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

Fetal Thyroid Hormone

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

Links: Endocrine - Thyroid Development

Parathyroid

Parathyroid adult

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

Principal cells cords of cells

Parathyroid Development

Pharyngeal pouches

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

Links: Endocrine - Parathyroid Development

Thymus

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

Thymus Development

• Endoderm - third pharyngeal pouch
• Week 6 - diverticulum elongates, hollow then solid, ventral cell proliferation
• Thymic primordia - surrounded by neural crest mesenchyme, epithelia/mesenchyme interaction
  • Note in contrast to this historic image (shown here), current research has shown that the human thymic epithelium derives solely from the third pharyngeal pouch (as in the mouse).

Links: Endocrine - Thymus Development

Pancreas

Pancreas adult

pancreas structure

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

Pancreas Development

Pancreatic buds and duct developing

Stage22 pancreas

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

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

Pancreatic Islets

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

Pancreas Timeline

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

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

Adrenal

• Richly vascularized - arterioles passing through cortex, capillaries from cortex to medulla, portal-like circulation
• Fetal Cortex - produces a steroid precursor (DEA), converted by placenta into estrogen
• Adult Medulla - produces adrenalin (epinephrine), noradrenaline (norepinephrine)
• Fetal adrenal hormones - influence lung maturation

Adrenal cortical hormones - (steroids) Cortisol, Aldosterone, Dehydroepiandrosterone

• zona glomerulosa - regulated by renin-angiotensin-aldosterone system controlled by the juxtaglomerular apparatus of the kidney.
• zona fasciculata - regulated by hypothalamo-pituitary axis with the release of CRH and ACTH respectively.

Adrenal medullary hormones - (amino acid derivatives) Epinephrine, Norepinephrine

Adrenal Development

Week 10 adrenal gland

• Fetal Adrenals - fetal cortex later replaced by adult cortex
• Week 6 - fetal cortex, from mesothelium adjacent to dorsal mesentery; Medulla, neural crest cells from adjacent sympathetic ganglia
• Adult cortex - mesothelium mesenchyme encloses fetal cortex

Adrenal Cortex

• Late Fetal Period - differentiates to form cortical zones
• Birth - zona glomerulosa, zona fasiculata present
• Year 3 - zona reticularis present

Endocrinology - Adrenal Cortex Development

Adrenal Medulla

• neural crest origin, migrate adjacent to coelomic cavity, initially uncapsulated and not surrounded by fetal cortex, cells have neuron-like morphology
• 2 cell types - secrete epinepherine (adrenaline) 80%; secrete norepinepherine (noradrenaline* 20%

Links: Endocrine - Adrenal Development

Gonad

Female HPG axis

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

Gonad Development

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

Differentiation

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

Testis

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

Ovary

• X chromosome genes regulate ovary development

Corpus Luteum

Corpus luteum histology

A maternal endocrine organ that develops within the ovary in all mammalian species from the ovulating follicle. The key function of this endocrine organ is to maintain pregnancy in response to endocrine signals from the implanting conceptus (chorionic ganadotrophin). Corpus luteum steroidogenesis then alters the normal female reproductive cycle, maintains the endometrial lining of the uterus, and acts on the maternal endocrine system. The corpus luteum, depending upon the species, produces a range of androgens, estrogens and progesterone.

Links: Endocrine - Gonad Development | Menstrual Cycle | Estrous Cycle

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
• Progesterone-Associated Endometrial Protein (PAEP, pregnancy protein-14, PP14) - glycoprotein hormone from decidualized endometrium with possible immunoregulatory activities.
• 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

Other Endocrine

Endocrine Heart

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

Endocrine Kidney

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

GIT Endocrine

Enteric control of digestive function

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

Adipose Tissue

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

Links: Endocrine - Other Tissues

Endocrine Functional Changes

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

References

Journals

Endocrine Development This series is devoted to specific areas of fetal, neonatal, pediatric and adolescent endocrinology. It addresses a wide range of relevant issues in the context of a well defined subject and covers new areas of clinical and basic research.

Textbooks

Endocrinology - An Integrated Approach Stephen Nussey and Saffron Whitehead, St. George's Hospital Medical School, London, UK Oxford: BIOS Scientific Publishers; 2001. ISBN-10: 1-85996-252-1 Copyright © 2001, BIOS Scientific Publishers Limited. Bookshelf Link Chapter 1. Principles of endocrinology Chapter 2. The endocrine pancreas Chapter 3. The thyroid gland Chapter 4. The adrenal gland Chapter 5. The parathyroid glands and vitamin D Chapter 6. The gonad Chapter 7. The pituitary gland Chapter 8. Cardiovascular and renal endocrinology

Endotext De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Bookshelf Link

Reviews

Özen S & Darcan Ş. (2011). Effects of environmental endocrine disruptors on pubertal development. J Clin Res Pediatr Endocrinol , 3, 1-6. PMID: 21448326 DOI.

Search PubMed

Search Pubmed: Endocrine Development

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Additional Images

Embryonic Histology

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  Stage 22 - Pancreatic duct

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  Stage 22 - Adrenal gland

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  Week 10 - Adrenal gland

Adult Histology

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  Pineal (high power)

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  Thyroid (low power)

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  Thyroid (high power)

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  Parathyroid (low power)

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  Parathyroid (high power)

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  Pituitary - adenohypophysis

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  Pituitary - adenohypophysis

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  Pituitary - neurohypophysis

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  Adrenal - Cortex and Medulla

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  Adrenal - Cortical Zones

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  Adrenal - Zona Reticularis and Medulla

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  Pancreatic islet

Endocrine 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 (More? Thyroid Development) corticosteroid binding globulin - (CBG) binds and transports glucocorticoids in the plasma. Globin is synthesised in the liver. dehydroepiandrosterone - (DHEA, androstenolone) The fetal adrenal cortex produces dehydroepiandrosterone sulphate (DHEA-S) used by the placenta to produce estrogens. Postnatally an abundant circulating steroid produced in the adrenal gland. DHEA, androstenedione, and testosterone can be metabolized to epiandrosterone, and etiocholanolone. PMID 15635500] follicle stimulating hormone - (FSH) pituitary, protein hormone (More? Pituitary Development) 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 (More? Placenta Development) lutenizing hormone - (LH) pituitary, protein hormone melaocyte stimulating hormone - (MSH) pituitary, peptide hormone prolactin - (PRL) pituitary, peptide hormone (More? Pituitary Development) parathyroid hormone - (PTH) parathyroid, peptide hormone (More? Parathyroid Development) Rathke's pouch - The transient folding surface ectoderm from roof of the oral cavity that will form the anterior pituitary (hypophysis). in later development the connection with the oral cavity is lost. Named after Martin Heinrich Rathke (1793 – 1860) a German embryologist and anatomist. (More? Pituitary Development) thyroid hormone - (TH) thyroid,amino acid derivative (More? Thyroid Development) thyroid stimulating hormone - (TSH) pituitary, protein hormone (More? Pituitary Development)
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Cite this page: Hill, M.A. (2023, December 1) Embryology Endocrine System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_System_Development

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G