Hormones & Receptors Flashcards
Steroid hormone structure characteristics
- Lipophilic ==> permeate cell membranes
- hydrophobic ==> carried by carrier proteins in the blood stream
- Steroid bound by carrier = inactive
- only a small fraction (1-5%) exists in the free form (active form)
- Steroid hormones can linger in the blood for a long time and they have a long half life.
- e.g. estradiol
Peptide hormone structure characteristics
- relatively polar ==> can not permeate cell membranes
- hydrophillic ==> not carried by carrier proteins
- Peptide hormones have a short half-life because they move through the blood in their free form; they are easily degraded by proteases.
- e.g. GnRH
Unique characteristics of GH, prolactin, and insulin-like growth factor (IGF-1)
Growth hormone (GH), prolactin (PRL), and insulin-like growth factor (IGF-1)behave differently because they are not transported in the blood as free hormones.
Thyroid hormone structure characteristics
- derived from tyrosine
- iodine-dependent
- e.g. T4
Location and types of peptide hormone receptors
- Peptide and protein hormones can not move through cell membranes so their receptors are located on the plasma membrane of target cells.
- Receptors types include:
- G-protein coupled receptors
- Cytokine receptor family (with JAK/STAT signaling pathways)
- Epidermal growth factor receptor (EGFR) family with inherent tyrosine kinase activity
Peptide hormones ==> g-protein coupled receptors
- Epinephrine and Norepinephrine
- glucagon
- Somatostatin (SST)
- DA
- etc (most hypothalamic hormones)
Peptide hormones ==> cytokine receptor family
- prolactin
- GH
Peptide hormones ==> epidermal growth factor receptor family w/tyrosine kinase activity
- insulin
- IGF-1 (insulin-like growth factor)
Location/types of steroid and thyroid hormones
- Steroid/thyroid hormones can permeate cell membranes and their receptors are in the cytosol or nucleus.
- Receptor-hormone complexes bind to specific hormone responsive elements (HRE) on DNA which activate transcription of specific genes.
Mechanism of signaling of G-Protein Coupled Receptors
- Gs → ↑ Adenylyl cyclase → ↑ cAMP → ↑ PKA → Glucagon, hypothalamic
- Gi → ↓(inhibits) Adenylyl cyclase → ↓ cAMP → inhibits PKA → ↑ K+ → Somatostatin, dopamine
- Gq → ↑ Phosolipase C → PIP2 → IP3 → ↑ Ca2+ from ER → DAG → ↑ PKC
G-protein coupled mnemonics
Gs → Sam’s Assless Chaps At cAMP Provide Kind Accolades
Gq → Quinn plays craps, poops in casinos, drinks percolating Korean coffee
EGFR family receptor mechanism of signaling
- receptor itself has tyrosine kinase activity
- receptor then targets downstream effectors
- Example is insulin/insulin receptor activity
Cytokine receptor mechanism of signaling
- membrane receptors that activate intracellular tyrosine kinase called Janus Kinase
- Janus Kinase phosphorylates the receptor and the downstream kinase, which activates signal transduction and activators of transcription (STATs).
- This pathway is called JAK/STAT.
- Growth hormone and prolactin act this way.
MOA of steroid vs. thyroid hormones
- Steroid hormones bind to intracellular (cytosol/nuclear) receptor ==> receptor hormone complex ==> binding @ hormone responsive element on genomic DNA ==> transcription of specific genes
- Thyroid hormones T4 and T3 act through a similar mechanism as steroid hormones.
- TRH and TSH, however, are peptides and act through GPCR’s.
Main targets of regulation of hormone synthesis/release
- @ receptors
- via feedback loops
- @ mechanism/type of release of hormones
Characteristics of regulation of hormone release
- Pulsatile → in matter of minutes pulse may happen and then no release at all
- Circadian → levels vary throughout day
Characteristics of feeback loops regulating hormones
- Type 1 → Hormone is the regulated variable. Example is cortisol.
- Type 2 → Plasma concentration of a metabolite or mineral acts as the regulated variable. Example is glucose levels in blood are regulated by insulin and counterregulatory hormones
Characteristics of regulation of hormones @ receptors
- Chronic increased levels of a hormone causes the receptors to become internalized
- Spare receptors; 90% of receptors on cell surface are inactivated, but the cellular signalling is unchanged for the active receptors.
