growth hormone
DESCRIPTION
Growth Hormone overview. Thanks to @marietoinette and @SeLipar PuTus for letting me share their slides.TRANSCRIPT
بسم الله الرحمن
الرحيمDone by : Khaled Abd Ul-Karim Daif
ID : 432
Head of department : Dr. Maha Gamal
Supervised By: Dr Maged
Haron
Growth Hormone
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.
The History of the Pituitary Gland.
•The earliest history of the pituitary gland dates back to Ancient Egypt (around 1365 BC) where a portrait, of the Pharaoh at the time (Akhenaton), shows signs of acromegaly. Galen, in 150 AD, was the first to describe the pituitary, and he proposed that its role was to drain the phlegm from the brain to the nasopharynx.•In the early 18th century, They pituitary-portal blood system was dicovered.• In 1772, Acromegaly was discribed. In 1794, Diabetes Insipidus was differentiated from diabetes mellitus. In 1887, Minkowski was the first to link the expansion of the pituitary gland to a number of clinical symptoms. Within a few years it was accepted that it was the anatomical growth of the gland that produced the symptoms.
5-6 wks
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)• Hypophyseal pouch becomes the anterior pituitary (adenohypophysis)
Histology of Pituitary Gland
Growth Hormone (GH)
Name : Growth hormone (also called somatotropin) Source of production : Adenohypophysis (Acidophilic cells in pars distalis known as somatotrophs).Chemical structure : peptide hormone composed of 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.
GH Functions
1. 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.
• 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 somatotrophs and potently stimulates secretion of growth hormone.
Regulation of GH Secretion
GH levels
• Plasma GH level: in children (5-8 ng/ml) and in adults (2-4 ng/ml)
• Some factors may elevate the level temporarily as decrease in blood glucose and FFA levels - Fasting and starvation conditions - physical stress - sleep - sex hormones.
• Other factors may depress it as obesity- aging - cortisol - somatostatin.
mechanism of release
• requires specific signal transduction systems (cAMP and/or calcium influx and/or mobilization of intracellular calcium) and/ or tyrosine kinase(s) and/or nitric oxide (NO)/cGMP
mechanism of action
• GH binding to two GHRs causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both. These events recruit or activate a variety of signaling molecules
Growth hormone usesAgricultural Applications of Growth Hormone: In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, but it is not legal to use GH in raising cows for beef, cattle feeding, dairy farming and the beef hormone controversy. Use in poultry farming is illegal in the United States. Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin ) approved by the FDA but all applications have been withdrawn.
Replacement therapy: Treatment with exogenous GH is indicated only in limited circumstances, and needs regular monitoring due to the frequency and severity of side-effects. GH is used as replacement therapy in adults with GH deficiency of either childhood-onset (after completing growth phase) or adult-onset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being.
Performance enhancement: Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional
ACROMEGALY
andGIGANTISM
ACROMEGALY
DEFINITION
Chronic metabolic disorder
in which there is too much
growth hormone and the
body tissue gradually
enlarge
PATHOPHYSIOLOGY
Acromegaly is characterized by hypersecretion of growth hormone (GH),
which is caused by the existence of a secreting pituitary tumor in more
than 95% of acromegaly cases. Pituitary tumors are benign adenomas
and can be classified according to size (microadenomas being less than
10 mm in diameter and macroadenomas being greater than 10 mm in
diameter).3,4 In rare instances, elevated GH levels are caused by extra
pituitary disorders. In either situation, hypersecretion of GH in turn
causes subsequent hepatic stimulation of insulin-like growth factor-1
(IGF-1).1
SYMPTOMSBody odor
Carpal tunnel syndrome
Decrease muscle strength ( weakness )
Easy fatigue
Enlarge feet
Enlarge hands
Enlarge glands in the skin ( sebaceous
glands )
Enlarge jaw and tongue
Excessive height
Excessive sweating
Headache
Hoarseness
Joint pain
Limited joint movement
Sleep apnea
Swelling of bony areas around a joint
Thickening of skin, skin tags
Widely spaced teeth
Excess hair growth in females
Weight gain
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
INVESTIGATION
Visual field tests
Assessment of other pituitary hormones: prolactin, adrenal, thyroid, and gonadal hormones
MRI scan of pituitary and hypothalamus: more sensitive than CT scan
CT scan: for lung, pancreatic, adrenal or ovarian tumours that may secrete ectopic growth hormone or GHRH
Total body scintigraphy with radio-labelled OctreoScan® (somatostatin) to aid localisation of the tumour
Cardiac assessment: electrocardiogram, echocardiogram
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
COMPLICATIONS
Arthritis
Cardiovascular disease
Carpal tunnel syndrome
Colonic polyps
Glucose intolerance or diabetes
High blood pressure
Sleep apnea
Spinal cord compression
Uterine fibroids
Vision abnormalities
GIGANTISM
DEFINITION
Abnormally large growth due to
an excess of growth hormone
during childhood, before the
bone growth plates have closed.
CAUSES
The most common cause of too much growth hormone release is a noncancerous (benign) tumor of the pituitary gland. Other causes include:
Carney complex
McCune-Albright syndrome (MAS)
Multiple endocrine neoplasia type 1 (MEN-1)
Neurofibromatosis
If excess growth hormone occurs after normal bone growth has stopped, the condition is known as acromegaly.
SYMPTOMS
Delayed puberty
Double vision or difficulty with side (peripheral) vision
Frontal bossing and a prominent jaw
Headache
Increased sweating
Irregular periods (menstruation)
Large hands and feet with thick fingers and toes
Release of breast milk
Thickening of the facial features
Weakness
COMPLICATIONS
Delayed puberty
Difficulty functioning in everyday life due to large size and unusual features
Diminished vision or total vision loss
Embarrassment, isolation, difficulties with relationships, and other social problems
Hypothyroidism
Severe chronic headaches
Sleep apnea
PROGNOSISPituitary surgery is usually successful in limiting growth hormone production.
EXAMS & TESTSCT or MRI scan of the head showing pituitary tumor
Failure to suppress serum growth hormone (GH) levels after an oral glucose challenge (maximum 75g)
High prolactin levels
Increased insulin growth factor-I (IGF-I) levels
Damage to the pituitary may lead to low levels of other hormones, including:
Cortisol
Estradiol (girls)
Testosterone (boys)
Thyroid hormone
TREATMENT
Medications may be used to reduce GH release, block the effects of GH, or prevent growth in stature. They include:
Dopamine agonists, such as bromocriptine mesylate (Cycloset, Parlodel) and cabergoline (Dostinex), which reduce GH release
GH antagonist, pegvisomant (Somavert), which blocks the effects of GH
Sex hormone therapy, such as estrogen and testosterone, which may inhibit the growth of long bones
Somatostatin analogs, such as octreotide (Sandostatin) and long-acting lanreotide (Somatuline Depot), which reduce GH release
Radiation of the pituitary gland to regulate GH. This is generally considered the least desirable treatment option because of its limited effectiveness and side effects that can include obesity, emotional impairment, and learning disabilities.
Surgery to remove a pituitary tumor, which is the treatment of choice for well-defined pituitary tumors.
Other treatments of gigantism
Annu Rev Physiol. 1996;58:187-207,Molecular mechanism of growth hormone action,Carter-Su C, Schwartz J, Smit LS,Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Exp Biol Med (Maywood). 2004 Apr;229(4):291-302,Growth hormone secretion: molecular and cellular mechanisms and in vivo approaches,Anderson LL, Jeftinija S, Scanes CG,Department of Animal Science, Iowa State University, Ames, Iowa 50011, USA. [email protected]
GIRARD J, VEST M, ROTH N. Growth hormone content of serum in infants, children, adults and hypopituitary dwarfs. Nature. 1961 Dec 16;192:1051–1053.
ROTH J, GLICK SM, YALOW RS, BERSONSA Hypoglycemia: a potent stimulus to secretion of growth hormone. Science. 1963 May 31;140(3570):987–988.
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML; Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J.
Clin. Endocrino. Metab. 91 (5): 1621–34.
"Center for Veterinary Medicine Master" www.fda.gov. 2011-04-06
"Growth Promoters in Animal Production" 2006. Retrieved 2011-08-28.
Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrino. Metab. 91 (5): 1621–34.
Gaffney G (2008-03-17). "Steroid Nation: Review from Stanford says HGH no benefit as PED". Steroid Nation. Retrieved 2011-08-28.
Randall T (2008-03-17). "Athletes Don't Benefit From Human Growth Hormone, Study Finds". Bloomberg. Retrieved 2011-08-28.
Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR (May 2008). "Systematic review: the effects of growth hormone on athletic performance". Ann. Intern. Med. 148 (10): 747–58. PMID.
References
http://www.news-medical.net http://www.tev-tropin.com http://www.hypertropin.com http://www.youtube.com/user/ghdirect1 http://www.jintropin.cn http://www.vivo.colostate.edu
http://www.ncbi.nlm.nih.gov http://annals.org www.wikipedia.org
Thank You So Much..