24.6 Flashcards
Secretion of growth hormone is stimulated by ___ or ___.
GHRH or ghrelin
Somatostatin is the same as ___ and somatotropin is the same as ___.
Somatostatin - GHIH or growth hormone inhibiting hormone, from the hypothalamus (opposite of GHRH)
Somatotropin - growth hormone
Growth hormone is a peptide so bioavailability is zero after ___ administration.
Oral
The half-life of GH is ___.
Short
Need multiple doses, and parenteral (due to degradation via oral/GI tract)
GHRH and ghrelin together have a ___ effect on the release of growth hormone.
Synergistic
What are the 3 ways to treat excess GH/acromegaly?
Remove tumour (if relevant) Reduce GH release e.g. somatostatin analogues or dopamine agonists e.g. bromocriptine Inhibit GH action using a GH antagonist - pegvisomant
___ receptors bind to ___ and are internalised - so using a radioactive version of the same ligand, we can image and localise tumours.
Somatostatin receptors bind to somatostatin -> internalisation of the somatostatin receptor
Use radioactive somatostatin (octreotide)
To reduce GH secretion, ___ can be administered. But it has a short half-life due to rapid enzymatic cleavage and rapid ___ elimination.
Somatostatin (i.e. GHIH)
Enzymatic cleavage and renal elimination
Somatostatin has a very low half-life so researchers incorporated ___-amino acids into the structure because it is less susceptible to proteolytic cleavage -> increases half-life.
D-amino acids - ‘unnatural’
L-amino acids are natural
Examples of somatostatin analogues with D-amino acid replacements are ___ and ___.
Octreotide and lanreotide
To inhibit the action of GH, try using GH ___
Antagonists
Glycine at position ___ in human growth hormone is essential for its activity.
120
GH receptors ___ on ligand binding, therefore there are 2 binding sites on growth hormone itself.
Dimerise
2 binding sites on GH?
1 is high affinity - for first binding to monomer
Site 2 is to bind to the other monomer to dimerise
If there is no site 2, GH receptors bind but there is NO dimerisation!
G-120K-GH is an antagonist with high affinity - site _ is functional, but there is disruption of site _ binding by a lysine residue. But this antagonist has a ___ half-life!
1 is functional
Site 2 is disrupted - cannot dimerise!
Short, like GH
PEGylation is a process used to increase the __-__ of molecules by attaching polyethylene glycol to ___ residues.
Half-life
Lysine residues!
To try and increase the half-life of G-120K-GH, researchers tried PEGylation but it significantly reduced the ___ of it because of the two essential ___ residues in site 1.
Affinity
Lysine!
PEGylation decreased the affinity of G-120K-GH because of the essential site 1 lysine residues, so researchers substituted these residues to produce ___ - with a ___ half-life and adequate ___.
Pegvisomant
Long half-life
Adequate affinity
___ isotopes of iodine are used to ablate the thyroid gland. ___ isotopes of iodine compete with ___ isotopes so in cases of nuclear fallout, you can administer ___ isotopes to protect from effects of ___ iostopes.
Radioactive isotopes -> ablation of thyroid gland (sometimes used to treat hyperthyroidism)
Stable isotopes of iodine compete with radioactive isotopes
Give stable isotopes to protect from effects of radioactive isotopes
Thioamine drugs like ___ and ___ can be used to decrease production of TH or conversion of T4 to T3.
Carbamizole or propylthiouracil
Treatment of hypothyroidism using ___
Thyroxine (T4)
T4 binds to thyroxine binding globulin with high affinity so it has a long half-life and is protected from renal filtration
The half-life of thyroxine is approximately ___ days so it can accumulate slowly and onset of action may be low -> poor compliance. You can’t use a loading dose either due to risk of ___ problems
7
Cardiac
T3 is less strongly bound than T4 and has a ___ half-life
Shorter
Maybe use in emergencies e.g. severe hypothyroid or myxoedema coma
