Hormone Synthesis and Action Flashcards
What are peptides and proteins?
→ Water soluble
→ Made from large precursors
→ Prohormones
What are steroids and iodinated tyrosines?
→ Lipid soluble
→ Made from low weight molecular weight precursors
What is a pre pro hormone?
→ Signal sequence + prohormone
What is a prohormone?
→ Hormone + peptide sequence
What is the inactive form of vasopressin called?
→ Arginine vasopressin
What are the steps in insulin synthesis?
1) transcription to mRNA
2) Excision of introns to mRNA
3) Removal of signal sequence and formation of disulfide bonds in RER
4) Pre-pro insulin → pro insulin
5) Transferred to golgi and excision of C peptide
What is StAR?
→ Steroidogeneic acute regulatory protein
→ Protein that transports cholesterol to the inner mitochondrial membrane
How is cholesterol made into steroids?
→ Lipid stores in the cell
→ Stimulus activates a second messenger
→ Cholesterol transfers from cytoplasm into mitochondria
→StAR protein transports cholesterol to the inner mitochondrial membrane
What is cholesterol cleaved into and how?
→ Cleaved to pregnenolone
→ Side chain cleavage enzyme P450cc
What are the hormones cholesterol can be converted into?
Cholesterol ↓ Pregnenolone ↓ Progesterone → Aldosterone Hydroxylated progesterone → Cortisol + Androgens
What enzymes do androgens need and what do they do?
→ Aromatase
→ Converts androgens to estrogens
What is aromatase deficiency in men?
→ Unable to synthesize estrogens from androgens
→ No epiphyseal closure (bone development)
→ Long stature
What happens if children have aromatase deficiency?
Girls
→ Virilization of XX fetuses
→Ambiguous genitalia
Boys
→ Precocious puberty
→ Early sexual development
What are the 8 steps for the synthesis of thyroid hormones?
1) Active uptake of iodide into follicular cell
2) Transport across the apical membrane
3) Oxidation of iodide to iodinated intermediate by thyroid peroxidase
4) Iodination of tyrosine residues of thyroglobulin
5) Coupling of iodinated tyrosine residues
6) Storage of T3 and T4
7) Uptake of thyroglobulin droplets into follicle cell
8) release of T3 and T4
Where is iodide hormone stored?
→ Colloid
What is goitre?
→ Enlargement of the thyroid gland
What is Graves disease?
Antibodies to the TSH receptor act on the thyroid gland
→ Stimulates excess thyroid hormones and can cause ophthalmopathy
Proptosis- eye bulging. the immune system attacks the muscles and fatty tissues around and behind the eye
What are properties of peptide and protein hormones?
→ Water soluble → cell surface receptors
→ Activate second messengers and/or enzymes
→ Cytoplasmic and nuclear effects
What are properties of steroid hormones?
→ Lipophilic
→ Intracellular receptors in cytoplasm or nucleus
→ Receptors are transcription factors
What are the two surface receptors?
→ G protein linked receptors
→ Tyrosine kinase domains
What is involved the G protein signalling pathway?
→ Adenyl cyclase
→ cAMP
→ PKA
What is involved the PIP pathway?
→ PIP
→ DAG
→ IP3
→ Ca2+
What are the major pathways in tyrosine kinase?
→ RAF/ MEK/ ERK
→ PI3 kinase / AKT
→ JAK/ STAT
What is mTOR a target for?
→ Cancer drugs
Hormone Synthesis and Action
What can mTOR go on to do after being phosphorylated?
- promoting of ribosome synthesis/protein synthesis
- inhibiting of protein degradation
- stimulating protein uptake and metabolism
What are two conditions if you have a defective G coupled receptor?
→ Thyroid adenoma
→ Precocious puberty
What are 2 conditions if you have a defective G protein?
→ McCune Albright syndrome
- fibrous dysplasia of bone
- cafe au lait pigmentation
→ Combined precocious puberty
What is the C domain of steroid hormone receptors?
→ DNA binding region
What are the functional domains of steroid receptors?
→ A-F
What is the C domain made up of?
→ 2 zinc fingers
→ Slot into helix of DNA
What are the steps for steroid hormone binding?
1) Hormone crosses cell membrane
2) Heat shock protein dissociates from receptor
3) hormone binds to receptor and dimerization occurs and translocate to nucleus
4) Binds to hormones response element on DNA
5) Along with other transcription factors, transcription is initiated
What can kinases do?
→ Activate transcription factors
What are the causes of goitre?
Lack of iodine in the diet leads to deficiency in T3 and T4 (hypothyroidism)
Graves disease (hyperthyroidism)
Thyroid adenoma
How does low T3 and T4 cause goitre?
reduced T3 and T4 lead to lack of inhibition of TSH
TSH responsible for thyroid gland growth
