Unit 03: Growth Hormone

Question 1

what are somatotrophs

Answer 1

• of anterior pituitary gland
• produce and secretes growth hormone

Question 2

how is growth hormone secreted? what mediates its anabolic effects?

Answer 2

• GH is first expressed at high concentrations during puberty - secreted in a striking pulsatile manner with large pulses usually occuring at night durign sleep
• anabolic effetcs are mediated by insulin-like growth factors, especially insulin like growth factor 1 (IGF-1)

^hormone released into circulation by hepatocytes in response to stimulation by GH

GH directly promotes lipolysis, gluconeogenesis and protein synthesis.

• both GH and IGF-1 promote skeletal and soft tissue growth

Question 3

what expressed IGF-1

Answer 3

several cells types are capable of producing IGF-1

the liver contributes the overwhelming majority of detectable IGF-1 in the circulation.

Question 4

receptors of IGF-1 and GH

Answer 4

• similar receptors in structure and action
• binding of hormone results in dimerization and activation of an intracellular signal transduction pathway leading to cell growth

Question 5

describe the Hypothalamic-pituitary–growth hormone axis in health and disease.

Answer 5

• in normal axis, hypothalmic secretion of GH releasing hormone (GHRH) or ghrelin sitmulates release of GH while somatostatin inhibits release of GH
• secreted GH then stim the liver to synthesize and secrete insulin-like growth factor 1 (IGF-1) which promotes systemic growth
• IGF-1 also inhibts GH release from the anterior pituitary gland

Question 6

describe GH deficiency

Answer 6

common cause of retarded growth or possible dwarfism

• can be heritable or acquired and can be due to a hypothalamic defect (GHRH) or pituitary problem like a tumor, traume or infection
• results in problems in cardiovascular system, psychosocial issues, decreased muscle and bone mass, inc body fat (esp in face), low energy and reduced strength, poor libido and sleep patterns

Question 7

how to diagnose GH deficiency

Answer 7

• obtain serum GH levels - want both basal and stimulated
• few treatments can be applied to individuals with GH deficiency

Question 8

describe treatment with recombinant human GH

Answer 8

ex somatropin

• given subcutaneous in evening 3-7 times a week
• often used in children that have deficiencies like chronic renal disease and turner syndrome
• children would hae thier IGF-1 levels and their height monitored over time and therapy would be cont until growth spurt has ceased
• in adults therapy is introduced for ind with GH deficienc, AIDS wasting, short bowel syndrome and is thought to paly role in anti-aging

*GH therapy has shown to be abused in athletes due to its anabolic properties.

Question 9

what is Mecasermin?

Answer 9

rhIGF-1/rhIGFBP-3

• another GH therapy and it used frequesntly in children with GH receptor defects or antibodies to GH

(rhIGFBP-2 is the binding protein that is responsible for maintaining IGF-1 half-life)

Question 10

what is sermorelin

Answer 10

synthetic form of GHRH

• can be sued to reat GH deficiency
• not useful if the deficiency occurs at level of the pituitary gland but can be used diagnostically to differentiate between hypothalamic and pituitary disease

Question 11

what is the result of GH excess

Answer 11

• can cause gigantism - excessive linear growth when epiphyses of growth plates are still unfused in younger individuals

*rare condition and significantly shortens lifespan

• GH excess in adulthood can cause acromegaly (uncommon),
• GH exces could also cause arthropathy (form of arthritis), visceromegaly (enlargement of abdominal organs), respiratory and cardiovascular problems and gastrointestinal tumours.

^ diagnosed b elevates serum IGF-1 or GH usually caused by a tumour of the anterior pituitary

*surgery foten successful treatment if the tumour present is microadenoma, otherwise radiation can also be applied.

Question 12

drug treatment for GH excess

Answer 12

• octreotide (Sandostatin) is a somatostain analogue that inhibits GH release

pegvisomant (Somavert) is a GH antagonist that decreases IGF-1

Question 13

what is prolactin? describe the structure of the receptor

Answer 13

peptide hormone that is produced in the anterior pituitary by cells called lactotrophes

• simialr structure ot GH receptor and ti activates a second messenger cascade following receptor binding
• prolactin is responsible for breast development and milk production following birth

Question 14

treatment for prolactin deficiencies

Answer 14

no treatment for hypoprolactemia

Question 15

what can result from hyperprolactemia

Answer 15

• foten associated with a prolactin secreting tumour
• may cause inappropriate breast development and lactation which can be particularly problematic in men
• Reproductive difficulties can also be associated with prolactin disturbances.

Question 16

what hormone is released by hypothalamus to decrease prolactin secretion for pituitary

Answer 16

dopamine

*dopamine like drugs can be used to decrease prolactin

Question 17

what is bromocriptine

Answer 17

therapeutic agent that can be administered to stimulate D2 dopamine receptors in the anterior pituitary to decrease prolactin secretion

• can be applied if an individual is diagnosed with a prolactin secreting tumour which is called a prolactinoma

*Administration of dopamine analogues includes oral, intravaginal (reduces nausea observed with oral form) and subcutaneous deposits which are longer acting

Question 18

what is cabergolide (Dostinex)

Answer 18

therapeutic agent that can be administered to stimulate D2 dopamine receptors in the anterior pituitary to decrease prolactin secretion

• can be applied if an individual is diagnosed with a prolactin secreting tumour which is called a prolactinoma

*Administration of dopamine analogues includes oral, intravaginal (reduces nausea observed with oral form) and subcutaneous deposits which are longer acting

Question 19

what can result from a pituitary tumour

Answer 19

acromegaly bc inc secretion of GH and prolactin