Hormone Synthesis And Action Flashcards
Synthesis of protein / peptide hormones by transcription
-transcription of dna to rna
-post transcriptional processing rna to mature rna with excision if introns , modification of 3’ and 5’ ends
-translation of mRNA into protein using tRNA to transfer amino acids
-post translational processing - cleavage of large pre pro hormone, folding of protein, addition of sugar
What is the pre prohormone & pro hormone
Pre prohormone - signal sequence & prohormone
Pro hormone - hormone & peptide sequence
Synthesis of insulin
- transcription to mRNA
Excision of introns to messenger rna
Removal of signal sequence
Formation of disulphide bonds in RER
Pre proinsulin forms proinsulin
Transfer to Golgi apparatus
Excision of c peptide and packing into secretory granules
How is steroid synthesis controlled from cholesterol
- cholesterol Is bound to sterol carrier protein which is transported to the mitochondria
-StAR protein transports cholesterol to inner mitochondrial membrane
-cholesterol to progenolone by side chain cleavage and enzyme p450 scc
-between mitochondria and SER steroids synthesised by hydroxylase enzymes
Examples of steriod hormones
-androgen
-oestrogen
-progesterone
-cortisol
-aldosterone
Synthesis of thyroid hormones
- active uptake of iodide to follicular cells
- transport across apical membrane
-oxidation of iodine to iodinated intermediate by TPO which is activated by h2o2
-iodination of tyrosine residues by thyroglobulin
-coupling of iodinated tyrosine residues
-storage of t3 & t4 on colloid
-uptake of thyroglobulin droplet into follicles cells
Release and secretion of t3 &t4
Effects of steriod hormones in female
-oestrogen controls menstrual cycle , breast tissue development, fertility, reproductive organ development
Secondary sexual characteristics eg body hair
Effect of steriod hormones in males
-testosterone controls reproductive and supportive organs , development of sexual characteristics in men eg deeping of voice , body hair
What part of the structure of nuclear receptors is highly conserved
C domain , it is the dna binding region
What domains of nuclear receptors have transcriptional activity
A/B and E/F domains
Outline the structural organisation of nuclear receptors
A/B domain is the N terminal
C domain is the dna binding domain
D domain is the hinge domain
E- ligand binding domain
F-c terminal domain
What are the key characteristics of a nuclear receptor and their roles
Ligand binding domain -binds specific steriod molecules with high affinity
DNA binding domain- bind specific dna sequences
Activation function domains - recruits gene activation machinery
Describe the c domain of a nuclear receptor
- made of two zinc fingers which can slot into the helix of DNA
Steroid hormone action
Hormone crosses cell membrane
Heat shock protein dissociates from receptor
Hormone binds to receptor and dimerization occurs
Dimerized receptors translocate to the nucleus
Binds to the hormone response element on the DNA
Along with other transcription factors transcription is initiated
Some receptors located within the nucleus not the cytoplasm
Two types of diabetes
Type 1- autoimmune destruction of pancreatic islet - absolute insulin deficiency
Type 2 - insulin resistance , partial loss of insulin production
How is atherosclerosis linked to obsesity
- obesity leads to insulin resistance which then causes
Hyperglycaemia
Hypertension
Inflammation
Endothelial dysfunction
Impaired thrombolysis
Aromatase deficiency in men
- Aromatase is responsible androgens into oestrogen
This leads to decreased oestrogen levels and increased Androgen levels which is a hormonal imbalance that leads to
-delayed or incomplete puberty
-abnormal enlargement of breast tissue in men ( gynecomastia )
Infertility
Decreased bone density
Aromatase deficiency in women
- lack of estrogen production
Leads to infertility
Delayed or absent puberty in females
-increase facial hair growth , deepening of voice , male pattern baldness
-decreased bone mineral density
-menstrual irregularities
What is androgen insensitivity
Lack of a functional receptor , so complete lack of response to testosterone, XY embryos develop as females , developmental anomalies , infertility
What is androgen deficiency
Affects men of different ages
If occurs before puberty it can cause delayed puberty , developmental abnormalities,lack of secondary sexual characteristics eg no voice change, reduced muscle growth
In older men it leads to libido , impotence , loss of muscle mass
What is a goitre and causes
- enlargement of thyroid gland
- lack of iodine in diet leads to t3 & t4 deficiency
-Graves’ disease
-thyroid adenoma
How is Graves’ disease caused in terms of hormones
-auto antibodies to the tsh receptor act on thyroid gland which stimulates excess thyroid hormones and cause eye disease
Proptosis-bulging of eye
