True or False: Hormones are produced by organs.
False - hormones can be produced by individual cells
True or False: Hormones must be released into the blood stream.
False - there is paracrine/autocrine signaling, chemical mediators may be diffused into the interstitial space
True or False: Hormones exert its specific function.
What are the types of hormones according to structure?
- amino acid derivatives/amines
- proteins, peptides, and glycoproteins
- steroids - prostanoids/prostaglandins
Enumerate the amino acid/amine hormones
- thyroid homones
How are thyroid hormones synthesized?
Iodination of benzene ring of tyrosine
Give examples of thyroid hormones.
- T3 or triiodothyronine
- T4 or thyroxine
How are catecholamines synthesized?
Introduction of a second hydroxyl group in the benzene ring of tyrosine
Give examples of catecholamines.
norepinephrine, epinephrine, dopamine
How is melatonin synthesized?
Acetylation of the aliphatic amino group and hydroxylation of the indole ring of tryptophan
Enumerate the protein/glycoprotein hormones
- thyrotropin-releasing hormone (TRH), growth hormone (GH), and luteinizing hormone (LH)
What is peculiar about TRH, GH, and LH?
They all come from a common ancestral gene; they have similar basic structures but with different functions
What is the smallest hormone? Where is it produced?
TRH (3 amino acids), produced in the hypothalamus
What is peculiar about insulin production?
Analogues (from alternative splicing and post-translational modification) of insulin produce slightly different effects. This is significant for some patients that are resistant to certain types of insulin
Enumerate the steroid hormones
- cortisol - glucocorticoid - aldosterone - mineralocorticoid - DHEA-S, androstenedione - sex hormones - vitamin D metabolites
How are steroids produced?
Cholesterol undergoes modification of side chains, hydroxylation, and ring formation.
How are prostanoids or prostaglandins produced?
addition of oxygen atoms and cyclization of arachidonic acid
How are peptide and steroid hormones stored?
Peptide hormones are usually stored in granules, while steroids are usually free in the cytoplasm
How are peptide and steroid hormones transported in the blood?
Peptide hormones are usually free (faster action), while steroids are usually bound to transport proteins.
What are the types of hormones according to mechanism of action?
- hormones that bind to intracellular receptors (i.e. lipophilic hormones)
- hormones that bind to cell-surface receptors
How are hormones classified according to function?
- growth and development
- energy availability
Types of cell-to-cell interactions:
- autocrine (short distance to cells of the same type)
- paracrine (short distance to cells of different type)
- endocrine (long distance via blood stream)
- neurocrine (long distance via blood stream produced by a nerve cell)
preprohormone vs prohormone vs hormone
- preprohormone - produced in ribosomes; signal peptide is still attached
- prohormone - produced in RER; signal peptide is cleaved off
- hormone - produced in Golgi apparatus; copeptide is cleaved off; stored in granules
examples of special precursor molecules:
- propiomelanocortin (POMC) - precursor for ACTH (adenocorticotropic hormone)
- glucagon precursor - precursor for glucagon (pancreas) or glucagon-like peptide (GLP, in L cells of intestine)
Types of hormone release
- vesicular e.g. proteins, peptides, and catecholamines (stored in granules)
- non-vesicular e.g. steroids and eicosanoids (lipophilic hormones), diffuse across plasma membrane out of the cell
- hybrid (combination) e.g. thyroid hormones
How are non-vesicular hormones protected from degradation?
by being bound to transport proteins e.g. thyroglobulin for thyroid hormones and cortisol-binding protein for cortisol
mechanism of peptide hormone release
1. Stimulus (depends on hormone)
2. Activation of second messenger (only for some).
3. Increase in intracellular calcium drives contraction of microtubules
and microfilaments attached to secretory granules
4. Bring secretory granules to cell membrane
5. Granule fuses with cell membrane
6. Hormone is released (exocytosis).
How are steroids transported?
Steroids are bound to transport proteins, to protect them from metabolism and renal clearance (wastage)
How are peptide hormones transported?
Free - short-lived, destroyed by circulating proteases, have immediate effect
protein hormones that are bound to carrier protein:
GH and IGF-1
Cells that eventually receive the hormone in circulation
specialized structure that will bind a particular hormone
Parts of the receptor
- recognition domain - binds to the hormone
- coupling domain - involved in signal transduction; intracellular, mediates signaling of receptor
three conditions for hormone to produce an effect
- Hormone must be recognized by receptor.
- Hormone-Receptor Complex must have the ability to produce signal
generation in cytoplasm/nucleus.
- There must be available effector proteins/enzymes and other
machinery to manifest response.
Will there be an effect if receptor is weakly bound to a homologue of the original hormone?
Yes, and the effects are those produced by the original hormone.
Significance of Human Chorionic Gonadotropin (HCG)
- structural homologue of TSH (thyroid-stimulating hormone) and LH (luteinizing hormone)
- released during pregnancy by placenta
- may activate thyroid hormones
- causes gestational transient thyrotoxicosis associated with hyperemesis gravidarum (morning sickness)
Hormone mechanisms of action
- G-protein-linked receptors
- G-protein second messengers
- enzyme-linked receptors
How many subunits are there in a G-protein? Enumerate:
three: alpha, beta, and gamma
What are the functions of the subunits of G-proteins?
alpha-subunit - binds to receptors, to effector molecules, and to GDP and GTP
beta-gamma-subunit (dimer) - may serve to attach the G-protein to the plasma membrane
What are the basic components of a G-protein pathway?
- G-protein complex
- Target enzyme or channel
Cation required for the G-protein cycle
What are the main effector systems used by G-proteins?
- adenylyl cyclase-cAMP system
- plasma membrane phospholipids/phospholipase C pathway
- calcium-calmodulin system
What does the adenylyl cyclase-cAMP system do?
It catalyzes the formation of cAMP from ATP with Mg2+ as cofactor. This increases the intracellular cAMP levels.