Lecture 14: Endocrine Intro, Receptors Flashcards
Function of the endocrine system
Multi-organ coordination and communication via nonspecific blood-borne hormones
Primary endocrine pathology
Issue in gland making the end hormone
Secondary endocrine pathology
Disturbance in regulatory factors going to an otherwise normal gland
4 chemical types of hormones
- Amines
- Tyr derived e.g. epi, norepi - Peptides
- Short AA chains - Proteins
- Longer AA chains - Steroids
- Derived from cholesterol
Major roles of endocrine system
- Maintain internal environs.
- Maintain energy balance
- Growth/development
- Reproduction
Features of peptide/protein hormones
- Polar, soluble (+ epi)
- Bind cell memb. receptors; can’t cross membrane
- Free transport in blood
- Regulate cell activity
Features of steroid hormones
- Nonpolar, low solubility (+ thyroxine)
- Carrier proteins in blood
- Cross memb. freely; bind IC receptors
- Regulate gene expression
Features of amine hormones
Varies by hormone.
Plasma transport Kd
Dissoc. constant Kd describes when half of receptors are bound
- Free + bound hormone Eq [H][P] / [HP]
Properties of hormone receptor interactions
- Simple, reversible rxn
- Saturable
- High affinity
- High specificity
- Receptors only located on target cells
3 classes of cell membrane receptors
- G protein linked
- Kinase linked (RTK, Ser/Thr, MAPK, JAK/STAT)
- Ca/Calmodulin linked
GPCRs
- 7 transmembrane helices
- G protein coupled (heterotrimeric GTPases)
G protein cycle
- Ligand binds
- GDP out, GTP in on Gα
- Gα/GTP dissociates
- Gα/GTP activates effector -> signal transduction
- Gα hydrolyzes GTP to GDP
- Gα/GDP reassociates
Beta-adrenergic receptor desensitization
- Beta-adrenergic receptor kinase (β-ARK) phosphorylates GPCR in cytoplasm
- β-arrestin binds -> prevents Gα/GDP reassoc.
Receptor Tyr Kinases (RTKs)
- 1 transmemb. helix
- Ligand binds -> IC kinase dimerization -> trans-auto-Pi -> signal tranduc.
Janus Kinase / Signal Transducer and Activator of Transcription (JAK/STAT)
- Dimerizes w/ ligand -> kinase domain recruit -> trans-auto-Pi -> STAT effector
Steroid hormone receptor interaction
- Steroid hormone binds IC receptor
- Stabilizing Heat Shock Protein displaced from receptor
- Nuclear translocation + dimerization
- Binding to Hormone Response Element on DNA
Domains of steroid hormone receptor superfamily
- Transactivation, hormone binding, dimerization domains
- DNA-binding domain (Zn-finger motif); binds HRE palindrome
Sexual differentiation process
- Female Mullerian duct is default
- XY -> AMH (MIH) -> Mullerian degen.
- T -> internal male genitalia (Wolffian ducts)
- DHT -> external male genitalia
Androgen Insensitivity Syndrome
Lack of response to androgens (T) -> genetic male w/ mature female phenotype
- No T response -> no LH downreg -> high T, high LH -> T converted to E by aromatase
- No pubic hair (controlled by T)
