Case 4 Flashcards by Jonathan Allan

What is the structure of the GH receptor?

Homodimer

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Through what mechanism does the GH receptor signal?

JAK-STAT

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Outline the JAK-STAT receptor mechanism

GH binding causes homodimerisation
JAK domains transphosphorylate
STAT recruited and phosphorylated
Phosphorylated STAT- transcription factor

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How would you describe the tyrosine kinase activity in GHR?

Associated activity

Enzyme associated

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How would you describe the tyrosine kinase activity in IGF-1R?

Inherent activity

Enzyme domain

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LH, TSH and FSH receptors are all examples of…

G protein coupled receptors

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What are the major steps in GPCR activation?

GTP replaces GDP
a and by subunits dissociate
G protein activates adenylate cyclase
Cyclic AMP produced

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What intracellular signalling pathways are activated by GPCR stimulation?

MAP kinase and PI3K pathways

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What are myeoid cells?

Smooth muscles in seminiferous tubules that help move sperm towards the epididymis

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‘Female, short stature, delayed puberty’

Turners syndrome 45X

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‘Male, tall but not in puberty, low IQ’

Klinefelters syndrome 47XY

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‘hypogonadism, lack of smell’

Kallmans syndrome
Olfactory and (collateral) GnRH neurone damage

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‘Headaches, vomit, fatigue, thrist, lack of growth’ (unisex)

Craniopharyngeoma

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‘Lack of growth with sufficient IGF1 levels’

Hypothyroidism

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What is cellular hypertrophy?

Increase in cellular protein synthesis causing an increase in size and functional capacity
A cellular response to trophic hormones

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What is hyperplasia?

The enlargement of tissues directly as a result of an increase in cell division

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What type of receptor is the IGF-1 receptor?

RTK

Integral enzymatic domain

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Through what downstream pathway does IGF-1R signal?

MAP and PI3K

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From where is GH released?

Somatotrophs in anterior pituitary

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How is GH released?

Pulsatile frequency, mainly at night

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What type of hormone is IGF-1?

Peptide hormone

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Where is IGF-1 produced?

Liver and bone

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What is the function of GH at the liver?

IGF-1 production

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What is the function of GH at the bone/cartilage?

Stimulation of chondrocytes @ zone of proliferation

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What is the function of GH on adipose tissue?

Increases lipolysis

What is the function of GH on muscle?

Increases protein synthesis | Increase in amino acid uptake

What is the function of IGF-1 on muscles?

Increases protein synthesis | Increase in amino acid uptake

What is the function of IGF-1 on bone?

Increase in osteoblast and osteoclast activity | Increase in collagen I synthesis

What is the function of IGF-1 on cartilage?

Stimulation of chondrocytes @ zone of proliferation

What is the effect of IGF-1 on peripheral glucose uptake?

Stimulates preipheral glucose uptake

Where is the IGF-1 receptor expressed?

In every cell hence IGF-1's global growth promoting effects

In what manner is IGF-1 produced?

Non-pulsatile

In addition to IGF-1, what other protein is released upon GH binding to the liver?

Somatomedin

How is GH release regulated?

Tight -ve feedback control Somatomedin binds somatotrophs in anterior pituitary Somatostatin released from hypothalamus Somatostatin inhibits GH release from somatotrophs

What hormone controls appetite?

Ghrelin

What hormone controls the release of thyroid stimulating hormone?

Thyrotropin releasing hormone

From where is TSH released?

Anterior pituitary | Thyrotrophs

Outline the mechanism involved in the production of T3 and T4

Dietary iodide absorbed Converted to Iodine Thyroglobulin donates Tyrosine to form mono/diiodotyrosine in colloid cells

What is the name of the protein that is transported in complex with Thyroxine hormones?

Thyroid binding globulin

What is the difference between T3 and T4?

T4 - inactive | t3 - active

What is the function of thyroid stimulating hormone?

Binds follicular cells | Stimulates production of T4 which is then converted into T3 to increase basal metabolic rate

What type of receptor is the thyroid hormone receptor?

Intracellular

To which region of the epiphyseal plate does t3 bind?

Region of hypertrophy

What are the additional affects of t3?

Increased sensitivity to adrenaline (fight or flight response)

How do testosterone and estrogen effect thyroxine production?

Increases the production of t3 and t4 by stimulating TSH release from anterior pituitary

How do testosterone and estrogen effect GH and IGF-1 levels?

Stimulate GH production from somatotrophs (and hence IGF-1)

What protein is necessary for GnRH protein production? What does this explain?

Leptin | Earlier puberty in high BMI children

What are the effects of testosterone during puberty?

Penis, scrotum and testicular enlargement Hair development on chest/axilla/genitals Hypertrophy of laryngeal mucosa Increased skin thickness

LH stimulates what cell to produce testosterone?

Leydig

What cells are responsive to FSH?

Sertoli | Causes SC's to aid spermatogenesis

What are the functions of the sertoli cells?

Nourishment of developing spermatocytes Secretory functions Phagocytosis of cytoplasm Blood testes barrier

What are the different stages of spermatogenesis?

Germline epithelia ---spermatogonia -- (mitosis) -- primary spermatocyte -- (meiosis I) -- secondary spermatocyte -- (meiosis II) -- spermatid -- (differentiation) -- sperm cells

From what cell type is estrogen secreted in males?

Sertoli

What is thought to initiate puberty?

Kisspeptin

How is a childs predicted adult height calculated?

(height of mother + height of father +/- 13cm for boy or girl) / 2

What is the most accurate measurement of whether a child is growing well?

Calculate mid parental centile Plot on target centile range graph If more than 2 centiles away from mean, then child has abnormal growth pattern

What cell types generate osteoblasts?

Osteoprogenitor cells (from mesenchymal stem cells)

What are volkmanns canals?

Signalling channels in compact bone that run perpendicular to osteons

What are the 3 types of cartilage?

Hyaline (precursor to bone) Fibro (eg. vertebral discs) Elastic (eg. epiglottis)

What is articular cartilage?

A type of hyaline cartilage that lines the moving surfaces of a joint

What collagen fibres are found in hyaline cartilage?

Type II collagen

What are the five zones of the epiphyseal plate?

Reserve, proliferative, hypertrophy, calcification, newly formed bone

Give two other names for spongy bone

Trabecullar | Cancellous

What is appositional bone growth?

Bone growth in diameter due to bone formation beneath the periosteum

What are the 6 steps involved in embryonic long bone development?

i. cartilage body development ii. Bony collar formation (diaphysis) iii. Chondrocyte hypertrophy and calcification iv. Chondrocyte death and medullary cavity formation v. Primary ossification centre formed vi. Blood supply exploration (secondary ossification centre formation)

Case 4 Flashcards

(65 cards)