growth axis

Question 1

how is GH released? and what underlies the mechanism?

Answer 1

in pulastile manner, perhaps due to somatostatin

Question 2

what is somatostain coupled to, and how does it reduce GH secretion?

Answer 2

Coupled to Gai- this is linked to PLC which negatively regulates adenylate cyclase, this reduces GH secretion (and not synthesis) because it reduces the effect of GHRH within the somatotrops

Question 3

what is GHRH coupled to?

Answer 3

this is coupled to Gas - this is linked to cAMP-CREB - PKA pathway - which regulates gene transcription and causes somatotroph cell proliferation

Question 4

how is responsible for the pubertal spurt in GH?

Answer 4

estrogens and androgens and this is because the synthesise the anterior pituitary to GHRH

Question 5

explain how the GH receptor work?

Answer 5

The GH receptor is part of the cytokine receptor family. receptor has a single transmembrane portion, and is found in inactivated dimer state (if no ligand is bound), once ligand binds autophosphorylation of the JAK-2 residues occurs, and this recruits STAT (via its tyrosine kinase activity). STAT causes a change in gene transcription, producing IGF-1 and SOCS (this inhibits and terminates this signalling cascade)

Question 6

how does GH cause insulin resistance?

Answer 6

GH increases lipolysis and this reduces glucose metabolism. it also seems that SOC-1 and SOC-3 inhibit PI-3K directly- so insulin resistance can also be intracellular mediated

Question 7

how does GH cause insulin resistance?

Answer 7

GH increases lipolysis and this reduces glucose metabolism. it also seems that SOC-1 and SOC-3 inhibit PI-3K directly- so insulin resistance can also be intracellular mediated

Question 8

what is the gene GH-N associated with?

Answer 8

this is associated with post-natal growth - they’re expressed in the anterior pituitary

Question 9

what is the gene GH-V and CS associated with?

Answer 9

this is associated with in utero growth, they’re expressed in the synctiotrophoblast

Question 10

what are the metabolic actions of GH?

Answer 10

synergies with cortisol and antagonises the effect of insulin and this means it reduces glucose metabolism (hence diabtogenic when in excess)

increases lipolysis and NEFA release, this is enhanced in fasting states (Contributes to insulin resistance)

increase in protein synthesis

Question 11

what are the indirect effects of GH mediated through IGF-1?

Answer 11

growth promotion, clonal expansion of tissue and growth of bone, soft tissue and viscera

Question 12

what is the fusion of the growth plates dependant on?

Answer 12

oestrogen

Question 13

what is the most important enzyme required for growth plate closure?

Answer 13

aromatise which converts androgens to oestrogens

Question 14

when do we start requiring GH for growth?

Answer 14

after the 1st year, and this is because growth during the 1st year is dependant on the nutritional status, GH receptors do not start appearing until 7 months

Question 15

what is the effect of oestrogen and progesterone on GH

Answer 15

They increase its relaase by synthesising the AP to GHRH

Question 16

what is the effect of thyroid hormone on GH?

Answer 16

Increases its release, because it directly promotes its transciprtion

Question 17

what is the affect of the adrenal gland on GH?

Answer 17

the adrenal gland releases hormones that inhibit GH (cortisol)

Question 18

when is oxandrolone used?

Answer 18

this is used in delayed puberty, it is a weak androgen which is not aromatised (therefore does not cause plate fusion) just increase amount of GH release

not used in females, because risks masculinisation

Question 19

what is the provocative test?

Answer 19

this is when insulin is given, this suppresses glucose, therefore, we’d expect an increase in the level of GH

this is known as the insulin tolerance test- very helpful in identifying classical idiopathic GH hormone deficiency

Question 20

what is the suppressor test?

Answer 20

this is when glucose is given, and this suppresses GH- if there is a timor secreting GH no decline will be seen in GH levels

Question 21

describe GH secretion?

Answer 21

secreted in a pulsatile fashion, with peaks during periods 2 and 3 of the sleep cycle.

people with delayed sleep, have delayed peaks in their GH secretion

Question 22

what is PCOS?

Answer 22

This is the most common caused of decreased or absent menstruation with detectable oestrogen levels

Question 23

what are the classical observations made in pseudo-hypoparathryodism

Answer 23

exessivel short 4th metacarpal, severe mental retardation and marked kyphosis

Question 24

what are the classical observation in Junvenile Cushing’s

Answer 24

central adiposity, plethoric face, abdominal striae

Question 25

what is the classical appearance of a female with Turner’s syndrome

Answer 25

they have a webbed neck

the lack of chromosome means no gonadotrophin secretion and this limits growth potential

Question 26

what are the classical signs of hypothryodism?

Answer 26

low T3/T4 AND GH also low (because thyroid hormone bind to the promoter region of growth hormone to directly increase its expression

Question 27

what is the hormonal profile of delayed puberty?

Answer 27

normal GH and low LH and FSH

Question 28

what is the hormonal profile for anorexia nervosa?

Answer 28

low GnRH, GH and cortisol raised. hypothalamic turn-off

Question 29

what is the hormonal profile for anorexia nervosa?

Answer 29

low GnRH, GH and cortisol raised. hypothalamic turn-off

Question 30

what is the difference between the hormonal profiles in classical GH deficiency and Laron syndrome

Answer 30

Laron syndrome:

• normal or High GH
• no IGF-1

GH deficiency:
- low GH 
- low IGF-1 
- also responds to treatment via GH 
laron syndrome will not because it is a problem with receptor function