Growth hormone and Insulin- like growth factor

Describe the normal physiologic function of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) Recognize the history, clinical signs and laboratory abnormalities seen in pituitary dwarfism (GH deficiency) Recognize the history, clinical signs and laboratory abnormalities seen in acromegaly (GH excess) in cats and dogs Understand the physiologic principles of testing for these different pathologic conditions

Where is growth hormone released from

Anterior pituitary gland, from the somatotrops

Where is the growth hormone primary target and what happens here

• PRimary target is the liver

• liver will produce IGF 1 growth factor

• hormone which triggers growth, metabolism and repair

What 6 inputs go into the hypothalamus and stimulate the anterior pituitary somatotrops to release growth hormone…

• physical exertion

• fasting

• stress

• low glucose

• protein rich food

• thyroid hormone

• sex steroid hormone

DOP no llearn these, but depending on the stimuli this will either trigger Growth hormone RELEASING hormone… IR growth hormone inhibitirng hormone. This acts on the anterior pituotary gland and will determine how much, or if GH will be produced.

• GH stimulated from puberty

What are the 2 x negative feedback mechanisms to regulate the production of growth hormone

• TOo much IGF-1 present in blood (produced from the liver) will send a signal to the anterior pituitary to release growth inhibitory horomone to limit the growth and metabolism increase which comes with growth hormone…

• OR Too much growth hormone

How does Growth Hormone trigger an intracellular response…

• Growth hormone receptor present in most cells in the body - Tyrosine Kinase receptor

• JAK/ STAT signalling pathway (single transducer activator of transcription)

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What are the 2 actions of Growth hormone (IGF)

2x responses…

Short term = Starvation response…

• Lipolysis (mobilising lipids from adipose stores)

• Insulin antagonism (lowers its affects)

• Direct action of growth hormone..

Long term = Promotes growth…

• Growiwng animals

• protein synthesis

• mediated by IGf - 1

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What are the 2 affects of growth hormone

1) Promotes Growth

2) Starvation response

What are the 2 responses from growth hormone

• Starvation response

• Growth response

What is the stimuli for GH release (starvation response)

• Low blood glucose

• low free fatty acids

• low prptien

• trauma/ stress

• excersize

What are the 4 physiological affects of growth hormone when illicitng a starvation response ( using up our bodies stores due to reduced food availibility..

• rapid catabolic actions (hyperglycaemia (increasing blood glucose)

• INcreasing protein synthesis

• lipolysis (to enhance the fat use…)

• Carbohydrates - promote hyperglycemia.. (decreases glucose transport, increases insulin antagonism, increases gluconeogenesis..

What does growth hormone do in terms of the frowth response..

Growing is more proteions, therefore more growth hormone will make proteins faster

• faster transcription

• faster translation

• faster amino acid transport

• decrease catabolism from protien into amino acids

What is the growth response time and intermediated by…

• long hypertrophic action s

• mediated by insulin like growth factors..

• (local GH is also produced in the mammery gland)

Where is IGF 1 produced, what does it do, and how is its half life increased..

• Mimics the effects of Insulin of growth (stimulated by GH BUT does not affect the blood glucose concentrations…)

• PRoduced by differenet tissues (mainly the liver)

• Paracine and autocrine affects, binds to carrier protiens to increase their half life… IGF t1/2 = 20 hours.. GH t1/2 = 20 mins

• PULSITILE SECRETION?

What is the primary function of IGF -1 - What does it do…

• Main source = liver

• increases chrondrogenesis

• increases osteogenic cell replication and encourgaes deposition for NEW BONE

• e.g. Helps with Chondral Ossification so that chondrocytes —> Osteoblasts..

Bone grwoth review

In the presence of growth plates, IGF 1 and growth hormone will allow the bone to lengthen, Chondrocytes - osteoblasts. BOnes lengthen.

What is pituitary dwarfism signalment

• Heriditary in German sessions

• congenital spontaneous mutation, noAdenohypohysis and therefore no somatotrophs so no growth hormone..

• Autosomal recessive conditions…

What causes pituitary dwarfism and how does this occour

• Pituartory cells never differentiate as no transcription factor is coded for

• Defect occours after corticotrope differentiation (acth NOT affected) BUT GH TSH prolactin and gonadotrops reducd..

• can accompany a pituatory cyst (fluid filled sac where the pituatory gland should have been)

• Propotionate growth retardation, chunkal alopecia as hair wont regrow..

What does pituitary dwarfism look like initially

• Brigth and alert dogs as when born placental growth is relient on IGf1 NOT growth hormone

• become lethargic, appetit decrease + systemically ill (runt of litter) may also develop secondary hypothyroidism

• can live to 5 years of age

• Can treated with GH but not liscened in EU, or can give progesterone which also stimulates GH..

What happens to pitutary dwarfism secually

• males will retian their testes

• Gemales will be in constant oestrus, females will ovulates

How can you diagnose Pituitary dwarfism

• Measure growth hormone BUT hard to measure directly as it is pulsitle and is a species specific protein..

• Decreased IGF 1 has a longer half life, no pulsatle secretions and is not as species specific, can use a human assay - therefore this test is preffered.

What is the pituatory dwarfism stimulation test..

• Baseline blood sample, inject GHRH ( growth hromone stimulant)

• GH should increase massivly but for a pituatory dwarf no increase as has no anterior pituatory gland..

What are the 2 diseases that can come from excessive growth hormone…

Before puberty = Giantism - massivly increased growth and the animals will end up very large. Giantism, become giants, this is from massive growth… (rare in vet med) (hyperglycaemia as G?H permamently antagonses insulin, maintains high glucose in blood)

AFter puberty = ACromegaly - develops AFTER puberty, fat hands and feet. ACro (limbs) Megaly (excessive + outgrowth) Long bones dont grow BUT may get a hump back, enlarged bone, membranouse bones continue to grow e.g. in skull - may see a large horse.. + increase organs and increase facial feature s e.g. tongue

Agromegaly in cat,s

• over shot under jaw

• enlarged head

• enlarged heart (greater than 2 intercostal spaces and larges than 2/3 of the rib space)

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Acromegly cats signalment

• Middle aged - old cats (90% males)

• Pituitary tumour which excretes excess GH

• Usually diabeteic at presentation BECAUSE excess GH = insulin resistance, high insulin requirement in diabetic cats, therefore causes diabetes mellitus

What is the signalment of acromegaly in DOG

• OLD FEMALE DOGS

• Endogenous progesterone - excess growth hormone..

• induction og GH gene in mammary glands, GH identical to pituitary GH

HOw do you diagnose acromegaly

IGF -1 concentrations

GH concentration

supportive clinical sings

CT or MRI for cats only to see pituatory tumout (males) In dogs it is females that are affected and this is because females produce progesterone which may induce excess GH production.