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Growth Hormone


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Growth Hormone overview.
Thanks to @marietoinette and @SeLipar PuTus for letting me share their slides.

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Growth Hormone

  1. 1. TABLE OF CONTENT Historical Note Molecular level of GH Development of Pituitary Gland Histology of the Pituitary Gland Hormones secreted from Pituitary Gland. Parts of Pituitary Gland. Pituitary Gland. Diseases found in Pituitary Gland. Diagrams. Functions of Pituitary Gland.
  2. 2. The History of the Pituitary Gland.•The earliest history of the pituitary glanddates back to Ancient Egypt (around 1365 BC) where a portrait, of thePharaoh at the time (Akhenaton), shows signs ofacromegaly. Galen, in 150 AD, was the first todescribe the pituitary, and he proposed that itsrole was to drain the phlegm from the brain tothe nasopharynx.•In the early 18th century, They pituitary-portalblood system was dicovered.• In 1772, Acromegaly was discribed. In1794, Diabetes Insipidus was differentiated fromdiabetes mellitus. In 1887, Minkowski was thefirst to link the expansion of the pituitarygland to a number of clinical symptoms. Withina few years it was accepted that it was the
  3. 3. Development of Pituitary Gland • From 6-8 weeks : • the neurohypophyseal bud grows inferiorly from the hypothalamus • the hypophyseal pouch grows superiorly from the roof of the mouth (Rathke’s pouch) • Neurohypophyseal bud becomes the posterior lobe (neurohypophysis) 5-6 wks • Hypophyseal pouch becomes the anterior pituitary (adenohypophysis)
  4. 4. Histology of Pituitary Gland
  5. 5. Growth Hormone (GH)Name : Growth hormone (also calledsomatotropin)Source of production : Adenohypophysis(Acidophilic cells in pars distalis known assomatotrophs).Chemical structure : peptide hormone composedof 191 a.a. presenting in many forms in plasma:-1) Normal human GH (known as hGH n) M.W. 22000.2) Variant human GH (known as hGH v) M.W. 20000.3) Desamino forms : less active.
  6. 6. GH Functions1. Stimulates division and multiplication of chondrocytes of cartilage.2. Increasing height in children and adolescents.3. Increases calcium retention, and strengthens and increases the mineralization of bone.4. Increases muscle mass through sarcomere hyperplasia.5. Promotes lipolysis.6. Increases protein synthesis.7. Stimulates the growth of all internal organs excluding the brain.8. Plays a role in fuel homeostasis.9. Reduces liver uptake of glucose.10. Promotes gluconeogenesis in the liver.11. Contributes to the maintenance and function of pancreatic islets.12. Stimulates the immune system.
  7. 7. Regulation of GH• Secretion Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach.• Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.• Somatostatin (SS) produced by several tissues in the body, including the hypothalamus, inhibits GH release.• Ghrelin secreted from the stomach binds to receptors on
  8. 8. • Plasma GH • requires • GH binding mechanism of action mechanism of releaseGH levels level: in specific to two children (5-8 signal GHRs causes ng/ml) and in transductio dimerizatio adults (2-4 ng/ml) n systems n of (cAMP GHR, activat • Some factors may elevate and/or ion of the the level calcium GHR- temporarily influx associated as decrease in and/or JAK2 blood glucose mobilizatio tyrosine and FFA levels n of kinase, and - Fasting and intracellul tyrosyl starvation ar calcium) phosphory conditions - and/ or lation of physical stress - sleep tyrosine both. These - sex kinase(s) events hormones. and/or recruit or
  9. 9. Growth hormoneusesAgricultural Applications of GrowthHormone: In the United States, it is legal togive a bovine GH to dairy cows to increasemilk production, but it is not legal to use GHin raising cows for beef, cattlefeeding, dairy farming and the beef hormonecontroversy. Use in poultry farming isillegal in the United States. Severalcompanies have attempted to have a versionof GH for use in pigs (porcine somatotropin )approved by the FDA but all applicationshave been withdrawn.Replacement therapy: Treatment withexogenous GH is indicated only in limitedcircumstances, and needs regularmonitoring due to the frequency andseverity of side-effects. GH is used asreplacement therapy in adults with GHdeficiency of either childhood-onset (aftercompleting growth phase) or adult-onset(usually as a result of an acquired pituitarytumor). In these patients, benefits havevariably included reduced fatmass, increased lean mass, increased bonedensity, improved lipid profile, reducedcardiovascular risk factors, and improvedpsychosocial well-being.
  10. 10. A LDEFINITION C Y RChronic metabolic Odisorder in which there is Mtoo much growth hormone Eand the body tissue Ggradually enlarge A
  11. 11. PATHOPHYSIOLOGYAcromegaly is characterized by hypersecretion of growthhormone (GH), which is caused by the existence of asecreting pituitary tumor in more than 95% of acromegalycases. Pituitary tumors are benign adenomas and can beclassified according to size (microadenomas being lessthan 10 mm in diameter and macroadenomas being greaterthan 10 mm in diameter).3,4 In rare instances, elevated GHlevels are caused by extra pituitary disorders. In eithersituation, hypersecretion of GH in turn causes subsequenthepatic stimulation of insulin-like growth factor-1 (IGF-1).1
  12. 12. SYMPTOMSBody odor glands ) Sleep apneaCarpal tunnel Enlarge jaw and Swelling of bonysyndrome tongue areas around a jointDecrease muscle Excessive height Thickening ofstrength ( weakness skin, skin tags) Excessive sweating Widely spaced teethEasy fatigue Headache Excess hair growthEnlarge feet Hoarseness in femalesEnlarge hands Joint pain Weight gain
  13. 13. DIFFERENTIAL DIAGNOSIS Pseudoacromegaly Presence of similar acromegaloid features in the absence of elevated GH or IGF-I levels Physiologic growth spurt during puberty Familial tall stature or large hands and feet Myxedema
  14. 14. INVESTIGATIONVisual field testsAssessment of other pituitary hormones: prolactin,adrenal, thyroid, and gonadal hormonesMRI scan of pituitary and hypothalamus: more sensitivethan CT scanCT scan: for lung, pancreatic, adrenal or ovarian tumoursthat may secrete ectopic growth hormone or GHRHTotal body scintigraphy with radio-labelled OctreoScan®(somatostatin) to aid localisation of the tumour
  15. 15. PROGNOSIS Pituitary surgery is successful in most patient, depending on the size of the tumor and the experience of the surgeon Without treatment the symptoms will get worse,and the risk of cardiovascular disease increase
  16. 16. COMPLICATIONSArthritis High blood pressureCardiovascular disease Sleep apneaCarpal tunnel syndrome Spinal cord compressionColonic polyps Uterine fibroidsGlucose intolerance or Vision abnormalitiesdiabetes
  17. 17. DEFINITION G S I MAbnormally large growth due Gto an excess of growthhormone during Achildhood, before the bone Ngrowth plates have closed. T I
  18. 18. CAUSESThe most common cause of too much growth hormone release is anoncancerous (benign) tumor of the pituitary gland. Other causesinclude: Carney complex McCune-Albright syndrome (MAS) Multiple endocrine neoplasia type 1 (MEN-1) NeurofibromatosisIf excess growth hormone occurs after normal bone growth hasstopped, the condition is known as acromegaly.
  19. 19. SYMPTOMSDelayed puberty Irregular periods (menstruation)Double vision or difficultywith side (peripheral) vision Large hands and feet with thick fingers and toesFrontal bossing and aprominent jaw Release of breast milkHeadache Thickening of the facial featuresIncreased sweating Weakness
  20. 20. COMPLICATIONSDelayed pubertyDifficulty functioning in everyday life due to large size and unusual featuresDiminished vision or total vision lossEmbarrassment, isolation, difficulties with relationships, and other socialproblemsHypothyroidismSevere chronic headachesSleep apnea
  21. 21. PROGNOSISPituitary surgery is usually successful inlimiting growth hormone production.
  22. 22. EXAMS & TESTSCT or MRI scan of the factor-I (IGF-I) levelshead showing pituitarytumor Damage to the pituitary may lead to low levels ofFailure to suppress other hormones, including:serum growth hormone(GH) levels after an oral Cortisolglucose challenge Estradiol (girls)(maximum 75g) Testosterone (boys)High prolactin levels
  23. 23. TREATMENTMedications may be used to Sex hormone therapy, such asreduce GH release, block the estrogen andeffects of GH, or prevent testosterone, which maygrowth in stature. They inhibit the growth of longinclude: bonesDopamine agonists, such as Somatostatin analogs, such asbromocriptine mesylate octreotide (Sandostatin) and(Cycloset, Parlodel) and long-acting lanreotidecabergoline (Dostinex), which (Somatuline Depot), whichreduce GH release reduce GH releaseGH antagonist, pegvisomant(Somavert), which blocks theeffects of GH
  24. 24. Other treatments of gigantismRadiation of the pituitary gland to regulate GH. This isgenerally considered the least desirable treatment optionbecause of its limited effectiveness and side effects that caninclude obesity, emotional impairment, and learningdisabilities.Surgery to remove a pituitary tumor, which is thetreatment of choice for well-defined pituitary tumors.
  25. 25. ReferencesAnnu Rev Physiol. 1996;58:187-207,Molecular mechanism of growth Practice Guideline". J. Clin. Endocrino. Metab. 91 (5): 1621–34.hormone action,Carter-Su C, Schwartz J, Smit LS,Department ofPhysiology, University of Michigan Medical School, Ann Arbor 48109- "Center for Veterinary Medicine Master" 2011-04-060622, USA. "Growth Promoters in Animal Production" 2006. Retrieved 2011-08-28.Exp Biol Med (Maywood). 2004 Apr;229(4):291-302,Growth hormonesecretion: molecular and cellular mechanisms and in vivoapproaches,Anderson LL, Jeftinija S, Scanes CG,Department of Animal Endocrine Societys Clinical Guidelines Subcommittee, Stephens PAScience, Iowa State University, Ames, Iowa 50011, USA. (May 2006). "Evaluation and treatment of adult growth deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrino. Metab. 91 (5): 1621–34.GIRARD J, VEST M, ROTH N. Growth hormone content of serum ininfants, children, adults and hypopituitary dwarfs. Nature. 1961 Dec Gaffney G (2008-03-17). "Steroid Nation: Review from Stanford says16;192:1051–1053. HGH no benefit as PED". Steroid Nation. Retrieved 2011-08-28.ROTH J, GLICK SM, YALOW RS, BERSONSA Hypoglycemia: a potent Randall T (2008-03-17). "Athletes Dont Benefit From Human Growthstimulus to secretion of growth hormone. Science. 1963 May Hormone, Study Finds". Bloomberg. Retrieved 2011-08-28.31;140(3570):987–988. Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, BendavidMolitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet E, Saynina O, Salpeter SR, Garber AM, Hoffman AR (May 2008).SM, Vance ML; Endocrine Societys Clinical Guidelines "Systematic review: the effects of growth hormone on athleticSubcommittee, Stephens PA (May 2006). "Evaluation and treatment of performance". Ann. Intern. Med. 148 (10): 747–58. growth hormone deficiency: an Endocrine Society Clinical     