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The endocrine system refers to the collection of glands of an organism that secrete hormones directly into the circulatory system to be carried towards a distant target organ. The major endocrine glands include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus, gastrointestinal tract and adrenal glands. The endocrine system is in contrast to the exocrine system, which secretes its hormones using ducts. The endocrine system is an information signal system like the nervous system, yet its effects and mechanism are classifiably different. The endocrine system's effects are slow to initiate, and prolonged in their response, lasting from a few hours up to weeks. The nervous system sends information very quickly, and responses are generally short lived. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The field of study dealing with the endocrine system and its disorders is endocrinology, a branch of internal medicine.

Special features of endocrine glands are, in general, their ductless nature, their vascularity, and commonly the presence of intracellular vacuoles or granules that store their hormones. In contrast, exocrine glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen.

In addition to the specialised endocrine organs mentioned above, many other organs that are part of other body systems, such as bone, kidney, liver, heart and gonads, have secondary endocrine functions. For example the kidney secretes endocrine hormones such as erythropoietin and renin.

A number of glands that signal each other in sequence are usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis.

As opposed to endocrine factors that travel considerably longer distances via the circulatory system, other signaling molecules, such as paracrine factors involved in paracrine signalling diffuse over a relatively short distance.

The word endocrine derives from the Greek words ἐνδο- endo- "inside, within," and κρίνειν krinein "to separate, distinguish".

Endocrine organs and known secreted hormones[edit]

Endocrine glands in the human head and neck and their hormones

Hypothalamus[edit]

Secreted hormone Abbreviation Produced by Effect
Thyrotropin-releasing hormone TRH Parvocellular neurosecretory neurons Stimulate thyroid-stimulating hormone (TSH) release from anterior pituitary (primarily)
Dopamine
(Prolactin-inhibiting hormone)
DA or PIH Dopamine neurons of the arcuate nucleus Inhibit prolactin released from anterior pituitary
Growth hormone-releasing hormone GHRH Neuroendocrine neurons of the Arcuate nucleus Stimulate Growth hormone (GH) release from anterior pituitary
Somatostatin
(growth hormone-inhibiting hormone)
SS, GHIH, or SRIF Neuroendocrine cells of the Periventricular nucleus Inhibit Growth hormone (GH) release from anterior pituitary
Inhibit thyroid-stimulating hormone (TSH) release from anterior pituitary
Gonadotropin-releasing hormone GnRH or LHRH Neuroendocrine cells of the Preoptic area Stimulate follicle-stimulating hormone (FSH) release from anterior pituitary
Stimulate luteinizing hormone (LH) release from anterior pituitary
Corticotropin-releasing hormone CRH or CRF Parvocellular neurosecretory neurons of the Paraventricular Nucleus Stimulate adrenocorticotropic hormone (ACTH) release from anterior pituitary
Vasopressin
(antidiuretic hormone)
ADH or AVP or VP Parvocellular neurosecretory neurons, Magnocellular neurosecretory neurons of the Paraventricular nucleus and Supraoptic nucleus Increases water permeability in the distal convoluted tubule and collecting duct of nephrons, thus promoting water reabsorption and increasing blood volume

Pineal body (epiphysis)[edit]

Secreted hormone From cells Effect
Melatonin Pinealocytes Antioxidant
Monitors the circadian rhythm including induction of drowsiness and lowering of the core body temperature

Pituitary gland (hypophysis)[edit]

The pituitary gland (or hypophysis) is an endocrine gland about the size of a pea and weighing 5 grams (0.18 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica) covered by a dural fold (diaphragma sellae). The pituitary is functionally connected to the hypothalamus by the median eminence via a small tube called the infundibular stem or pituitary stalk. The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain. The pituitary gland secretes nine hormones that regulate homeostasis and the secretion of other hormones.[citation needed]

Anterior pituitary lobe (adenohypophysis)[edit]

Secreted hormone Abbreviation From cells Effect
Growth hormone
(somatotropin)
GH Somatotrophs Stimulates growth and cell reproduction
Stimulates Insulin-like growth factor 1 release from liver
Thyroid-stimulating hormone
(thyrotropin)
TSH Thyrotrophs Stimulates thyroxine (T4) and triiodothyronine (T3) synthesis and release from thyroid gland
Stimulates iodine absorption by thyroid gland
Adrenocorticotropic hormone
(corticotropin)
ACTH Corticotrophs Stimulates corticosteroid (glucocorticoid and mineralcorticoid) and androgen synthesis and release from adrenocortical cells
Beta-endorphin Corticotrophs Inhibits perception of pain
Follicle-stimulating hormone FSH Gonadotrophs In females: Stimulates maturation of ovarian follicles in ovary
In males: Stimulates maturation of seminiferous tubules
In males: Stimulates spermatogenesis
In males: Stimulates production of androgen-binding protein from Sertoli cells of the testes
Luteinizing hormone LH Gonadotrophs In females: Stimulates ovulation
In females: Stimulates formation of corpus luteum
In males: Stimulates testosterone synthesis from Leydig cells (interstitial cells)
Prolactin PRL Lactotrophs Stimulates milk synthesis and release from mammary glands
Mediates sexual gratification
Melanocyte-stimulating hormone MSH Melanotropes in the Pars intermedia of the Anterior Pituitary Stimulates melanin synthesis and release from skin/hair melanocytes

Posterior pituitary lobe (neurohypophysis)[edit]

Secreted hormone Abbreviation From cells Effect
Oxytocin Magnocellular neurosecretory cells In females: uterine contraction during birthing, lactation (letdown reflex) when nursing
Vasopressin
(antidiuretic hormone)
ADH or AVP Parvocellular neurosecretory neurons Increases water permeability in the distal convoluted tubule and collecting duct of nephrons, thus promoting water reabsorption and increasing blood volume

Oxytocin and anti-diuretic hormone are not secreted in the posterior lobe, merely stored.

Thyroid[edit]

Secreted hormone Abbreviation From cells Effect
Triiodothyronine T3 Thyroid epithelial cell (More potent form of thyroid hormone)
Stimulates body oxygen and energy consumption, thereby increasing the basal metabolic rate
Stimulates RNA polymerase I and II, thereby promoting protein synthesis
Thyroxine
(tetraiodothyronine)
T4 Thyroid epithelial cells (Less active form of thyroid hormone)
(Acts as a prohormone to triiodothyronine)
Stimulates body oxygen and energy consumption, thereby increasing the basal metabolic rate
Stimulates RNA polymerase I and II, thereby promoting protein synthesis
Calcitonin Parafollicular cells Stimulates osteoblasts and thus bone construction
Inhibits Ca2+ release from bone, thereby reducing blood Ca2+

Alimentary system[edit]

Endocrine Alimentary system en.svg

Stomach[edit]

Secreted hormone Abbreviation From cells Effect
Gastrin (Primarily) G cells Secretion of gastric acid by parietal cells
Ghrelin P/D1 cells Stimulate appetite,

secretion of growth hormone from anterior pituitary gland

Neuropeptide Y NPY increased food intake and decreased physical activity. It can be associated with obesity.
Somatostatin D cells Suppress release of gastrin, cholecystokinin (CCK), secretin, motilin, vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), enteroglucagon

Lowers rate of gastric emptying

Reduces smooth muscle contractions and blood flow within the intestine.[1]

Histamine ECL cells stimulate gastric acid secretion
Endothelin X cells Smooth muscle contraction of stomach[2]

Duodenum (small intestine)[edit]

Secreted hormone From cells Effect
Secretin S cells Secretion of bicarbonate from liver, pancreas and duodenal Brunner's glands

Enhances effects of cholecystokinin, stops production of gastric juice

Cholecystokinin I cells Release of digestive enzymes from pancreas

Release of bile from gallbladder, hunger suppressant

Liver[edit]

Secreted hormone Abbreviation From cells Effect
Insulin-like growth factor (or somatomedin) (Primarily) IGF Hepatocytes insulin-like effects

regulate cell growth and development

Angiotensinogen and angiotensin Hepatocytes vasoconstriction

release of aldosterone from adrenal cortex dipsogen.

Thrombopoietin THPO Hepatocytes stimulates megakaryocytes to produce platelets[3]
Hepcidin Hepatocytes inhibits intestinal iron absorption and iron release by macrophages

Pancreas[edit]

Pancreas is a mixed endocrine and exocrine gland and it secretes both enzymes and hormones.

Secreted hormone From cells Effect
Insulin (Primarily) β Islet cells Intake of glucose, glycogenesis and glycolysis in liver and muscle from blood

intake of lipids and synthesis of triglycerides in adipocytes Other anabolic effects

Glucagon (Also Primarily) α Islet cells glycogenolysis and gluconeogenesis in liver

increases blood glucose level

Somatostatin δ Islet cells Inhibit release of insulin[4]

Inhibit release of glucagon[4] Suppress the exocrine secretory action of pancreas.

Pancreatic polypeptide PP cells Self regulate the pancreas secretion activities and effect the hepatic glycogen levels.

Kidney[edit]

Secreted hormone From cells Effect
Renin (Primarily) Juxtaglomerular cells Activates the renin-angiotensin system by producing angiotensin I of angiotensinogen
Erythropoietin (EPO) Extraglomerular mesangial cells Stimulate erythrocyte production
Calcitriol (1,25-dihydroxyvitamin D3) Active form of vitamin D3

Increase absorption of calcium and phosphate from gastrointestinal tract and kidneys inhibit release of PTH

Thrombopoietin stimulates megakaryocytes to produce platelets[3]

Adrenal glands[edit]

Adrenal cortex[edit]

Secreted hormone From cells Effect
Glucocorticoids (chiefly cortisol) zona fasciculata and zona reticularis cells Stimulates gluconeogenesis
Stimulates fat breakdown in adipose tissue
Inhibits protein synthesis
Inhibits glucose uptake in muscle and adipose tissue
Inhibits immunological responses (immunosuppressive)
Inhibits inflammatory responses (anti-inflammatory)
Mineralocorticoids (chiefly aldosterone) Zona glomerulosa cells Stimulates active sodium reabsorption in kidneys
Stimulates passive water reabsorption in kidneys, thus increasing blood volume and blood pressure
Stimulates potassium and H+ secretion into nephron of kidney and subsequent excretion
Androgens (including DHEA and testosterone) Zona fasciculata and Zona reticularis cells In males: Relatively small effect compared to androgens from testes
In females: masculinizing effects

Adrenal medulla[edit]

Secreted hormone From cells Effect
Adrenaline (epinephrine) (Primarily) Chromaffin cells Fight-or-flight response:
Noradrenaline (norepinephrine) Chromaffin cells Fight-or-flight response:
Dopamine Chromaffin cells Increase heart rate and blood pressure
Enkephalin Chromaffin cells Regulate pain

Reproductive[edit]

Endocrine reproductive system en.svg

Testes[edit]

Secreted hormone From cells Effect
Androgens (chiefly testosterone) Leydig cells Anabolic: growth of muscle mass and strength, increased bone density, growth and strength,

Virilizing: maturation of sex organs, formation of scrotum, deepening of voice, growth of beard and axillary hair.

Estradiol Sertoli cells Prevent apoptosis of germ cells[5]
Inhibin Sertoli cells Inhibit production of FSH

Ovarian follicle and corpus luteum[edit]

Secreted hormone From cells Effect
Progesterone Granulosa cells, theca cells Support pregnancy:[6]

Other:

Anti-inflammatory

Androstenedione Theca cells Substrate for estrogen
Estrogens (mainly estradiol) Granulosa cells Structural:

Protein synthesis:

  • Increase hepatic production of binding proteins

Coagulation:

Fluid balance:

Gastrointestinal tract:

  • Reduce bowel motility
  • Increase cholesterol in bile

Melanin:

Cancer:

Lung function:

Inhibin Granulosa cells Inhibit production of FSH from anterior pituitary

Placenta (when pregnant)[edit]

Secreted hormone Abbreviation From cells Effect
Progesterone (Primarily) Support pregnancy:[6]

Other effects on mother similar to ovarian follicle-progesterone

Estrogens (mainly Estriol) (Also Primarily) Effects on mother similar to ovarian follicle estrogen
Human chorionic gonadotropin HCG Syncytiotrophoblast Promote maintenance of corpus luteum during beginning of pregnancy

Inhibit immune response, towards the human embryo.

Human placental lactogen HPL Syncytiotrophoblast Increase production of insulin and IGF-1

Increase insulin resistance and carbohydrate intolerance

Inhibin Fetal Trophoblasts Suppress FSH

Uterus (when pregnant)[edit]

Secreted hormone Abbreviation From cells Effect
Prolactin PRL Decidual cells milk production in mammary glands
Relaxin Decidual cells Unclear in humans and animals

Calcium regulation[edit]

Further information: Calcium metabolism

Parathyroid[edit]

Secreted hormone Abbreviation From cells Effect
Parathyroid hormone PTH Parathyroid chief cell Calcium:
  • Stimulates Ca2+ release from bone, thereby increasing blood Ca2+
  • Stimulates osteoclasts, thus breaking down bone
  • Stimulates Ca2+ reabsorption in kidney
  • Stimulates activated vitamin D production in kidney


Phosphate:

  • Stimulates PO3-4 release from bones, thereby increasing blood PO3-4.
  • Inhibits PO3-4 reabsorption in kidney, so more PO3-4 is excreted
  • Overall, small net drop in serum PO3-4.

Skin[edit]

Secreted hormone From cells Effect
Calcidiol (25-hydroxyvitamin D3) Inactive form of vitamin D3

Targets[edit]

Endocrine miscelaneous en.svg

Heart[edit]

Secreted hormone Abbreviation From cells Effect
Atrial-natriuretic peptide ANP Cardiac myocytes Reduce blood pressure by:

reducing systemic vascular resistance, reducing blood water, sodium and fats

Brain natriuretic peptide BNP Cardiac myocytes (To a lesser degree than ANP) reduce blood pressure by:

reducing systemic vascular resistance, reducing blood water, sodium and fats

Bone marrow[edit]

Secreted hormone From cells Effect
Thrombopoietin liver and kidney cells stimulates megakaryocytes to produce platelets[3]

Skeletal muscle[edit]

In 1998, skeletal muscle was identified as an endocrine organ[11] due to its now well-established role in the secretion of myokines.[12][13] The use of the term myokine to describe cytokines and other peptides produced by muscle as signalling molecules was proposed in 2003.[14]

Adipose tissue[edit]

Signalling molecules released by adipose tissue are referred to as adipokines.

Secreted hormone From cells Effect
Leptin (Primarily) Adipocytes decrease of appetite and increase of metabolism.
Estrogens[15] (mainly Estrone) Adipocytes

Diffuse neuro-endocrine system (DNES)[edit]

The Diffuse neuro-endocrine system (DNES) comprises hormone-secreted cells, that have commonalities with neurons and are found in the Epithelium of organs of the body.

Major endocrine systems[edit]

The human endocrine system consists of several systems that operate via feedback loops. Several important feedback systems are mediated via the hypothalamus and pituitary.[16]

Interaction with immune system[edit]

Extensive bidirectional interactions exist between the endocrine system and the immune system.[17] Cortisol has major immunosuppressive effects,[18][19] and dopamine has immunomodulatory functions.[20] On the other hand, cytokines produced during inflammation activate the HPA axis at all three levels, sensible to negative feedback.[21] Moreover cytokines stimulate hepcidin release from the liver, which is eventually responsible for the anemia of chronic disease.[22]

In other species[edit]

A neuroendocrine system has been observed in all animals with a nervous system and all vertebrates have an hypothalamus-pituitary axis.[23] All vertebrates have a thyroid, which in amphibians is also crucial for transformation of larvae into adult form.[24][25] All vertebrates have adrenal gland tissue, with mammals unique in having it organized into layers.[26] All vertebrates have some form of renin-angiotensin axis, and all tetrapods have aldosterone as primary mineralocorticoid.[27][28]

Diseases[edit]

Disability-adjusted life year for endocrine disorders per 100,000 inhabitants in 2002.[29]
  no data
  less than 80
  80–160
  160–240
  240–320
  320–400
  400–480
  480–560
  560–640
  640–720
  720–800
  800–1000
  more than 1000
Main article: Endocrine diseases

Diseases of the endocrine system are common,[30] including conditions such as diabetes mellitus, thyroid disease, and obesity. Endocrine disease is characterized by disregulated hormone release (a productive pituitary adenoma), inappropriate response to signaling (hypothyroidism), lack of a gland (diabetes mellitus type 1, diminished erythropoiesis in chronic renal failure), or structural enlargement in a critical site such as the thyroid (toxic multinodular goitre). Hypofunction of endocrine glands can occur as a result of loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, hyperplastic or neoplastic change, or hyperstimulation.

Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine disease is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.[citation needed]

As the thyroid, and hormones have been implicated in signaling distant tissues to proliferate, for example, the estrogen receptor has been shown to be involved in certain breast cancers. Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of oncogenesis.[31]

Other types of signaling[edit]

The typical mode of cell signaling in the endocrine system is endocrine signaling. However, there are also other modes, i.e., paracrine, autocrine, and neuroendocrine signaling. Purely neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.

Autocrine[edit]

Main article: Autocrine signalling

Autocrine signaling is a form of signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cells.

Paracrine[edit]

Main article: Paracrine signalling

Paracrine signaling is a form of cell signaling in which the target cell is near the signal-releasing cell, altering the behavior or differentiation of those competent cells.

Juxtacrine[edit]

Main article: Juxtacrine signalling

Juxtacrine signaling is a type of intercellular communication that is transmitted via oligosaccharide, lipid, or protein components of a cell membrane, and may affect either the emitting cell or the immediately adjacent cells.

It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as connexons. The gap between the cells can usually be between only 2 and 4 nm.

Unlike other types of cell signaling (such as paracrine and endocrine), juxtacrine signaling requires physical contact between the two cells involved.

Juxtacrine signaling has been observed for some growth factors, cytokine and chemokine cellular signals.

Additional images[edit]

See also[edit]

References[edit]

  1. ^ Colorado State University – Biomedical Hypertextbooks – Somatostatin
  2. ^ Endo K, Matsumoto T, Kobayashi T, Kasuya Y, Kamata K (2005). "Diabetes-related changes in contractile responses of stomach fundus to endothelin-1 in streptozotocin-induced diabetic rats". J Smooth Muscle Res 41 (1): 35–47. doi:10.1540/jsmr.41.35. PMID 15855738. 
  3. ^ a b c Kaushansky K (May 2006). "Lineage-specific hematopoietic growth factors". N Engl J Med. 354 (19): 2034–45. doi:10.1056/NEJMra052706. PMID 16687716. 
  4. ^ a b Physiology at MCG 5/5ch4/s5ch4_17
  5. ^ Pentikäinen V, Erkkilä K, Suomalainen L, Parvinen M, Dunkel L (2000). "Estradiol acts as a germinal cell survival factor in the human testis in vitro". J Clin Endocrinol Metab. 85 (5): 2057–67. doi:10.1210/jc.85.5.2057. PMID 10843196. 
  6. ^ a b c d Bowen, R. (August 6, 2000) Placental Hormones. Colorado State University
  7. ^ Physiology at MCG 5/5ch9/s5ch9_13
  8. ^ Hould F, Fried G, Fazekas A, Tremblay S, Mersereau W (1988). "Progesterone receptors regulate gallbladder motility". J Surg Res 45 (6): 505–12. doi:10.1016/0022-4804(88)90137-0. PMID 3184927. 
  9. ^ Hormonal Therapy
  10. ^ Massaro D, Massaro GD (2004). "Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice". American Journal of Physiology. Lung Cellular and Molecular Physiology 287 (6): L1154–9. doi:10.1152/ajplung.00228.2004. PMID 15298854. 
  11. ^ Pedersen BK, Febbraio MA (October 2008). "Muscle as an endocrine organ: focus on muscle-derived interleukin-6". Physiological Reviews 88 (4): 1379–406. doi:10.1152/physrev.90100.2007. PMID 18923185. 
  12. ^ Pedersen BK, Febbraio MA (October 2008). "Muscle as an endocrine organ: focus on muscle-derived interleukin-6". Physiological Reviews 88 (4): 1379–406. doi:10.1152/physrev.90100.2007. PMID 18923185. 
  13. ^ Ostrowski K, Hermann C, Bangash A, Schjerling P, Nielsen JN, Pedersen BK (December 1998). "A trauma-like elevation of plasma cytokines in humans in response to treadmill running". The Journal of Physiology 513 (3): 889–94. doi:10.1111/j.1469-7793.1998.889ba.x. PMC 2231318. PMID 9824725. 
  14. ^ Pedersen BK, Steensberg A, Fischer C, et al. (2003). "Searching for the exercise factor: is IL-6 a candidate?". Journal of Muscle Research and Cell Motility 24 (2-3): 113–9. doi:10.1023/A:1026070911202. PMID 14609022. 
  15. ^ Frühbeck G (July 2004). "The adipose tissue as a source of vasoactive factors". Curr Med Chem Cardiovasc Hematol Agents 2 (3): 197–208. doi:10.2174/1568016043356255. PMID 15320786. 
  16. ^ Sherwood, L. (1997). "Human Physiology: From Cells to Systems". Wadsworth Pub Co. ISBN 0495391840. 
  17. ^ Turnbull AV, Rivier CL (January 1999). "Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action". Physiological Reviews 79 (1): 1–71. PMID 9922367. 
  18. ^ O'Connor TM, O'Halloran DJ, Shanahan F (June 2000). "The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia". QJM 93 (6): 323–33. doi:10.1093/qjmed/93.6.323. PMID 10873181. 
  19. ^ Tsigos C, Chrousos GP (October 2002). "Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress". Journal of Psychosomatic Research 53 (4): 865–71. doi:10.1016/S0022-3999(02)00429-4. PMID 12377295. 
  20. ^ Sarkar C, Basu B, Chakroborty D, Dasgupta PS, Basu S (May 2010). "The immunoregulatory role of dopamine: an update". Brain, Behavior, and Immunity 24 (4): 525–8. doi:10.1016/j.bbi.2009.10.015. PMC 2856781. PMID 19896530. 
  21. ^ Silverman MN, Pearce BD, Biron CA, Miller AH (2005). "Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection". Viral Immunology 18 (1): 41–78. doi:10.1089/vim.2005.18.41. PMC 1224723. PMID 15802953. 
  22. ^ Andrews NC (May 2004). "Anemia of inflammation: the cytokine-hepcidin link". The Journal of Clinical Investigation 113 (9): 1251–3. doi:10.1172/JCI21441. PMC 398435. PMID 15124013. 
  23. ^ Hartenstein V (September 2006). "The neuroendocrine system of invertebrates: a developmental and evolutionary perspective". The Journal of Endocrinology 190 (3): 555–70. doi:10.1677/joe.1.06964. PMID 17003257. 
  24. ^ Dickhoff, Walton W.; Darling, Douglas S. (1983). "Evolution of Thyroid Function and Its Control in Lower Vertebrates". American Zoologist 23 (3): 697–707. doi:10.1093/icb/23.3.697. JSTOR 3882951. 
  25. ^ Galton, Valerie Anne (1 January 1988). "The Role of Thyroid Hormone in Amphibian Development". Integrative and Comparative Biology 28 (2): 309–18. doi:10.1093/icb/28.2.309. JSTOR 3883279. 
  26. ^ Pohorecky LA, Wurtman RJ (March 1971). "Adrenocortical control of epinephrine synthesis". Pharmacological Reviews 23 (1): 1–35. PMID 4941407. 
  27. ^ Wilson JX (1984). "The renin-angiotensin system in nonmammalian vertebrates". Endocrine Reviews 5 (1): 45–61. doi:10.1210/edrv-5-1-45. PMID 6368215. 
  28. ^ Colombo L, Dalla Valle L, Fiore C, Armanini D, Belvedere P (April 2006). "Aldosterone and the conquest of land". Journal of Endocrinological Investigation 29 (4): 373–9. doi:10.1007/bf03344112. PMID 16699307. 
  29. ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002. 
  30. ^ Kasper (2005). Harrison's Principles of Internal Medicine. McGraw Hill. p. 2074. ISBN 0-07-139140-1. 
  31. ^ Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL (2004). "TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia". Science 303 (5659): 848–51. doi:10.1126/science.1090922. PMID 14764882. 

External links[edit]


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