L04 - Hormone synthesis and action Flashcards
What is the difference between endocrine and exocrine?
Endocrine:
- Secretes hormones into blood directly from cells
- Ductless glands
Exocrine (not part of endocrine system):
- Duct; glands secrete directly into target site via ducts or tubes
(- Enzymes)
- Release secretions outside body
What is comparative endocrinology?
Actions of hormones similar throughout evolution
What is clinical endocrinology?
Hormones related to pathology
What are mixed glands?
A gland that secretes in endocrine and exocrine fashion
e. g.
- Pancreas produces digestive juice + insulin, glucagon and somatostatin
- Mucous and serous cells in salivary glands (two different secretory cells)
What is the difference in the chemical coordinator between the endocrine system and NS?
Endo:
- Hormones
- Many diff types affecting diff specific tissue
- Some hormones secreted from nerve endings [neuro-endocrine]
NS:
- NT
- Few types, secreted only onto target tissue
What is the difference in the speed of effect between the endocrine system and NS?
Endo:
- Generally slow
NS:
- Generally rapid
What is the difference in the duration of effect between the endocrine system and NS?
Endo:
- Generally long lasting
NS:
- Generally short-lived
What is the difference in the localisation of effect between the endocrine system and NS?
Endo:
- Secreted into blood therefore widespread
NS:
- Secreted onto target cell so effect very localisd
What is a hormone?
- A substance secreted directly into the blood by specialised cells
- Carried in the blood to receptors on target organs
- Present in only minute concentrations in the blood and bind specific receptors in target cells to influence cellular reactions
What are the different mechanisms of chemical signalling?
- Intracrine
- Endocrine
- Paracrine
- Autocrine
- Neuroendocrine
What is intracrine signalling?
Generated by a chemical acting within the same cell
- Does not leave the cell
What is endocrine signalling?
Chemicals enter the general circulation and reach distant target cells
What is autocrine signalling?
Chemical acts on the same cell
- Leaves the cell
What is paracrine signalling?
Chemical commn between neighbouring cells within a tissue or organ
- Neighbouring cells, could be via local circ
What is neuroendocrine signalling?
Chemical released by a specialised group of cells into the circ and acting on a distant target tissue
- From neurosecretory cells to distant target cells
What is -ve feedback?
The process by which body sense change and activates mechanism to reduce it
- The final product of an endo cascade acts to inhibit the release of hormones higher up in the cascade
What is +ve feedback?
The process by which body senses change and activates mechanism to amplify it
What is an endocrine axis?
Functional grouping of endocrine glands that stimulate each other
- Target tissue for a hormone may be another endocrine gland
- Faults may occur along this axis
e. g.: Hypothalamo-pituitary adrenal (HPA) axis
What are the 3 main groups of hormones?
- Protein/ peptide hormones
- E.g. Insulin - Steroid hormones
- E.g. cortisol - Amine hormones
- E.g. Tyrosine
Describe protein/ peptide hormones
- Most common type of hormone, of aa
- Water sol (hydrophilic)
- Preformed and stored in membrane bound vesicles ready for release by exocytosis
- Produced on RER as large precursor molc - pre-prohormone
Pre-prohormone –> prohormone –> hormone
What is the benefit of a large precursor?
A large precursor allows structural specificity
- Cleaved via proteolysis
Give examples of protein hormones
- Insulin
- Pre-proinsulin –> Proinsulin –> Insulin + C-peptide - ACTH
- In the corticotroph, pre-pro-opiomelanocortin produces one ACTH (in other cells, gives diff hormones) - Thyrotropin releasing hormone (TRH)
Which proteases are involved in the formation of insulin from pre-proinsulin?
- Endoprotease
- PC2 and PC3
- Carboxypeptidase
- Cleavage of signal peptide and covalent S-S bonds
Which hormones have a common a subunit?
- TSH
- LH
- hCG
- FSH
- Common a subunit
- Unique beta subunit
- Confers specificity
- Each subunit starts off as a larger molc
Describe steroid hormones?
- All made from cholesterol
- Lipid soluble (lipophilic)
- Hormones from adrenal cortex and sex hormones (gonads)
- Synthesised as req and diffuse out of the cell (no exocytosis)
- Synthesised in SER from cholesterol derived from diet or from acetate
What is the rate limiting step of steroid hormone prod?
The first (and rate limiting step) is conversion of cholesterol to pregnenolone - Pregnenolone formed in mitochondrion but moves to ER for processing into hormones
Describe the production of steroid hormones
- In the nucleus - hydrolysis of esters and release of cholesterol
- In mitochondrion - cholesterol to pregnenolone
- In SER - processing of pregnenolone
- Leave by diff or facilitated
What is the movement of cholesterol to the mitochondria regulated by?
Movement of cholesterol to the mitochondrion is regulated by steroid acute regulatory protein (StAR)
- ACTH (via cAMP) regulates StAR activity and processing of cholesterol
Describe the secretion of steroid hormones
- Newly synthesised steroid hormones are rapidly secreted from the cell, with little if any storage
- Increases in secretion reflect accelerated rates of synthesis
Describe the excretion of steroid hormones
- Steroid hormones are eliminated by inactivating metabolic transformations and excretion in urine or bile`
Describe amine hormones
- Tyrosine derivatives bound together
- Small, non-polar molcs
- Soluble in plasma membranes
- Lipid soluble (lipophilic)
Describe the transport in blood for steroid and thyroid hormones
Need to be transported in blood by carrier protein to:
- Inc solubility in blood
- Inc half-life (inc sol = inc half life)
- Create readily accessible reserve in blood
- Not water soluble, therefore need carrier
- Specific binding proteins, e.g. Thyroid BG (TBG) and cortisol binding globulin (CBG)
- Non specific binding proteins, e.g. albumin - loose binding (aldosterone binds to albumin)
Describe the transport in blood for peptide hormones
Freely water soluble
What is the relationship between free and bound hormones?
Free and bound hormones are in equilibrium
Where is the site of action for peptide hormones?
Cell surface receptors
- GPCR (2nd messenger; intrinsic hormone)
- Hormone binding activates second messenger cascade
- Ultimately, there is a phosphorylation of proteins within the cell and the activated proteins bring about a change in cellular function
Where is the site of action for steroid/ thyroid hormones?
Intracellular receptors
- Receptors within the cytoplasm (or nucleus e.g. THR) of target cell
- Steroid/ thyroid hormone receptor superfamily)
What are ligand-inducible transcription factors
Hormone-receptor complex binds to specific ‘hormone response elements (HRE’s)’ in the promoter region of specific genes.
- This results in modification of gene transcription and protein synthesis
- These receptors are there described as ligand-inducible transcription factors
Where are water soluble proteins synthesised/ stored in?
ER and golgi
Where are lipid soluble proteins synthesised/ stored in?
Cytosol
How are water soluble proteins transported?
Free hormone
How are lipid soluble proteins transported?
Lipoprotein
How are water soluble proteins secreted?
Exocytosis
How are lipid soluble proteins secreted?
Diffusion
Where is the site of action for water soluble proteins?
Plasma membrane
Where is the site of action for lipid soluble proteins?
Genome
