Endocrine Kalra Flashcards
How many types of hormone?
three main types of hormone:
• amine
• steroid
• peptide.
Examples of amines, steroids, peptides?
Why is thyroxine diff? I.e. What is it and what does it act like?
Amine: catecholamines, serotonin, thyroxine
• Steroid: cortisol, aldosterone, androgens, oestrogens, progestogens and vitamin D
• Peptide: everything else! (made up of a series of amino acids).
Thyroxine is chemically an amine but it acts like a steroid. Vitamin D has the structure of a steroid
hormone and it acts like one.
Amines/Peptides: half life? Receptor acts on? Act via what?
Steroids: half life? Receptor acts on? Act via what?
Short half-life (minutes)
• Secretion may be pulsatile
• Act on a cell surface receptor
• Often act via a second messenger
Longer biological half-life (hours)
• Act on an intracellular receptor
• Act on DNA to alter gene expression
Amines/peptides: what 3 mechanisms intracellularly is signal transmitted?
Peptide and amine hormones act at the cell surface via specific membrane receptors. The signal is
transmitted intracellularly by one of three mechanisms:
• Via cAMP
• Via a rise in intracellular calcium
• Via receptor tyrosine kinases.
Action of amines/peptides???
All amines/peptides work via cAMP except PIG TAG
PIG: Prolactin/Insulin/anything with word ‘Growth’ in it #TyrKinase
PIG bind to TyK receptor @cell surface - > TyK receptor phosphorylates other prots - > cascade of prot phosphorylation - > gene transcription @ nucleus modulated
TAG: TRH Adr GnRH #Calcium
Hormone receptors linked to cAMP have how many transmembrane domains?
Hormones that RAISE the level of cAMP intracellularly (except somatostatin) act via what G protein?
Hormones that LOWER the level of cAMP (somatostatin) act via what G protein?
7 transmembrane domains
Hormones that raise the level of cAMP intracellularly (all hormones in this category except somatostatin) act via a stimulatory G-protein, ‘Gs’.
Hormones that lower the level of cAMP (somatostatin) act via an inhibitory G-protein, ‘Gi’.
Acromegaly G-protein relation??
McCune Albright Syndrome G-protein relation?? This leads to?? Whats this syndrome assoc with from a derm and bone POV? After what embryonic stage does mutation occur? How does this manifest??
PseudoHypoPT G-protein relation?? Spontaneously occurring/paternally inherited differs how (and is aka…?!) ??
The dysmorphic bone features are sometimes referred to as
‘??’ and can be present in what inherited form??
40% acromeg pts = an activating somatic mutation of Gs @ pit tumour - - > cells always switched on –> GH always being made
activating mutation of Gs early in embryonic development
–> hyperfunction of 1/+ endocrine glands –> PACT
Precocious
puberty (gonad hyperfunction),
Acromegaly (GH hypersecretion),
Cushing syndrome (adrenal
gland hyperfunction),
Thyrotoxicosis/hyperPT.
The syndrome is associated with
café-au-lait spots and polyostotic fibrous dysplasia.
As the mutation occurs after the zygote
stage, affected individuals are a mosaic and different patterns of tissue involvement may be seen
between individuals
@pseudoHypoPT:
If MATernally inherited, get inactivating germline mutations in Gs - - > PseudoHypoPT type 1A w/
- dysmorphia (short 4th/5th metacarpal) AND
- resistance to a variety of hormones that act via cAMP
(including PTH, TSH and FSH/LH).
Spontaneously occurring/paternally inherited mutations just cause the dysmorphic features alone (PseudoPseudoHypoPT).
The dysmorphic bone features are sometimes referred to as
‘Albright’s hereditary osteodystrophy’ and can be present in either the maternally or the paternally inherited form
The receptors for the hormones that release intracellular Calcium as 2nd messenger activate which G-protein??
Activate Gq -> activate cytoplasmic PhosphoLipase C (PLC) - > PLC releases Inositol TriPO4 (IP3) from membrane phospholipids - > IP3 binds to receptor @ endoplasmic reticulum -> Ca released from ER into cytoplasm -> Ca binds to Calmodulin -> affect metabolism
Summary:
Hormones, (TAG-TRH Adr GnRH) activateGq -> aPLC -> release IP3 from membrane phospholipid -> IP3 bind to ER receptor -> Calcium release from ER to cytoplasm -> Ca bind to Calmodulin -> Calmodulin affects metabolism
Which hormones act intracellularly?? Why?
SVT: Steroids, Vit D, Thyroxine
Cos they lipid soluble AF hence don’t need receptors.
Cos SVT hormones are lipid soluble AF, they can diffuse through the cell membrane - > bind to receptor @cytoplasm -> shedding of heat shock prots that protect that empty receptor -> hormone-receptor complex migrates to nucleus -> alters gene transcription
In illness, body closes down which unnecessary systems down? What orchestrates this?
which hormones may rise?
In starvation alone, what falls?
THINK ABOUT FLAG TOP
Hypothal orchestrates Fall in: TIG
TRH and assoc hormones
Insulin/IGF(GH rises though..)
GnRH and assoc hormones
Stress hormones rise: GAP
GH(IGF falls though..)/Glucagon,
ACTH(glucocorts)/Adr,
Prolactin
@starvation, all falls EXCEPT glucagon
@anorexia, all falls EXCEPT glucagon, GH & glucocorts
In obesity, what hormones are high?
Which hormones are low?
Which conversions/turnovers happen?
High: LDLs, Insulin, Androgens
Low: HDLs, GH
High:
- Androgen -> oest conversion
- Cortisol turnover (not hypercortisolism though!!!)
Munching ->?? release from ?? -> bind to ?? receptor -> ?? appetite
Leptin falls in?? , leptin rises in ??
Leptin d.proportional to ??
Persistently obese ppl =?? to leptin
Congen leptin def = obesity, hyperphagia = Tx with leptin
Munching -> Leptin release from adipocyte -> bind to hypothal receptor -> reduce appetite
Leptin falls in starvation, leptin rises in munching
Leptin d.proportional to fatness
Persistently obese ppl = resistant to leptin
Congen leptin def = obesity, hyperphagia = Tx with leptin
Ghrelin relationship with appetite and weight
Fasting -> ghrelin released from stomach -> hunger + gastric contraction, emptying
Gastrectomy -> ghrelin falls ->
less hunger + gastric contraction, emptying
