Hormone synthesis and action Flashcards
(25 cards)
How is iodine processed?
- Active uptake of iodide into follicular cell
- Oxidation of iodide to iodine by thyroid
peroxidase (TPO) - Iodination of tyrosine residues of
thyroglobulin and apical-colloid interface - Storage in colloid
- Uptake of thyroglobulin droplets into follicle
cell - Release and secretion of T3 and T4 stimulated
by TSH
Are peptide and protein hormones water or lipid soluble?
Water soluble
Therefore have cell surface receptors
Are steroid and thyroid hormones water or lipid soluble?
Lipophilic - intracelular receptors in cytoplasm/nucleus
Recpetors are transcription factors
What are the two cell signalling pathways for protein and peptide hormones?
- Adenyl cyclase and cAMP pathways + phophsoinositide signalling
- tyrosine kinase
Second messengers in G-protein linked
receptors
Adenylate cyclase - cAMP - PKA
Phospolipase C - DAG + IP3
DAG- PKC
IP3 - Ca+
What type of structure do steroid hormones have?
Small molecules with multi ringed structure
What are the name given to steroid hormone receptors?
Nuclear receptor
What do mineralocorticoids do?
Control salt and water balance
How are the different functional regions of the receptor defined?
Defined as domains
A-F
Name all the domains?
A/B = N-terminal domain
C = DNA binding domain
D = Hinge region
E = ligand bondng domain (LDB)
F= C-terminal domain
What does the LBD do?
Binds specific steroid molecules with high affinity
What does the DNA binding domain (DBD) do?
Binds specific DNA sequences
Activation function domain (AF1 & 2)
Recruits gene activation machinery, some
receptors have a secondary AF2 domain
towards the C-terminal
The same basic domains and structure are
shared with many of the major nuclear receptors
LBD
DBD
AF1
AF2
Explain the structure of the C domain?
DNA binding region
made up of 2 zinc fingers which can slot into the helix of the dna
What does aromatase do?
Converts androgens to oestrogens
aromatase defiency in men effects?
Unable to synthesise oestrogens
from androgens no
epiphyseal closure long
stature
Aromatase deficiency in women effects?
Virilisation of XX fetuses
Clitoromegaly
Ambiguous genitalia
Difference between androgen insensitivity and defiency (hypogandism)
Androgen insensitivity – is due to a lack of functional receptor, causing
complete lack of response to testosterone. XY embryos develop as female
Reduced androgen, if before puberty, it
can cause delayed puberty and developmental abnormalities and lack of
secondary sexual characteristics, eg no voice change, reduced muscle
growth, no growth spurt.
What is a goitre ?
Enlargement of thyroid gland
Causes?
* Lack of iodine in the diet leads to deficiency in T3
and T4 (hypothyroidism)
* Graves disease (hyperthyroidism)
* Thyroid adenoma
What is proptosis?
Bulging of eye
(causes by graves disease)
Autoantibodies to the
TSH receptor act on
the thyroid gland,
stimulate excess
thyroid hormones and
can cause eye disease
What are peptide and protein hormones derived from?
Large precursor molecules called pro-hormones
What are Steroids and iodinated tyrosines made from?
Low molecular weight precursors
Outline the synthesis of protein/peptide hormones with transcription
- Transcription of DNA to RNA
- Post-trancriptional processing
RNA to mature RNA etc - Translation
4.Post-translational processing cleavage
What is the dofference between pre-hormone and prohormone ?
Pre-prohormone = (signal sequence + prohormone)
Prohormone (hormone + peptide sequence(s)
