Hormones and Receptors Flashcards
Define hormones
Signaling molecules that traffic information from one point to another through soluble medium
What are the main classes of hormones?
- Steroids
- Monoamines
- Peptides
- Proteins
- Eicosanoids
Define endocrine, paracrine, autocrine and intracrine
- Endocrine: hormone produced in one tissue causes effect on target tissue at a distant location
- Paracrine: hormone acts locally, on a neighbouring cell
- Autocrine: hormone acts locally, on the secretory cell itself
- Intracrine: hormone acts on secretory cell without release from the producer cell
List 4 differences between endocrine and nervous sytems
- Nervous system is highly compartmentalized, endocrine system has distant targets
- Nervous system sends message instantly, endocrine system is delayed
- Nervous system has LOW ligand-receptor affinity, endocrine system has HIGH affinity
- Nervous system has a small volume of distribution (ex. synapse), endocrine system is large
Define endocrine glands
Ductless glandular structures that release hormone secretions
How are hormone levels regulated?
Explain the Scatchard equation
Knowledge of the concentration of bound and free ligand provides information about the ligand-receptor affinity and the total concentration of receptor.
Define agonist and antagonist
- Agonist: ligand that triggers the effector mechanism and produces biologic effects
- Antagonist: bind the receptor but do not activate the effector mechanism
What are the classifications of peptide hormone (and neurotransmitter) receptors?
- 7 transmembrane domain (ex. beta adrenergic, PTH, LH, TSH, GRH, TRH, ACTH, MSH, glucagon, dopamin, a2 adrenergic, somatostatin)
- Single transmembrane domain
- Growth factor receptors - intrinsic tyrosine kinase activity (ex. insulin, IGF, EGF, PDGF)
- Cytokine receptors - accessory protein with TK domain (ex. GH, prolactin, erythropoietin, CSF)
- TGF beta receptor - serine/threonine kinase
- Guanylyl cyclase-linked receptors (ex. natriuretic peptides)
Where are the following receptors commonly found:
- Peptide (and neurotransmitter)
- Steroid
- Peptide/neurotransmitter: plasma membrane
- Steroid: nuclear receptor
Draw a G protein coupled receptor
G proteins are heterotrimers. The identity of a G protein is defined by its ______ subunit.
Alpha
List the 4 subtypes of G proteins
- G alpha s (ex. beta adrenergic, TSH, glucagon) – activate adenylyl cyclase
- G alpha i (ex. alpha-2 adrenergic, muscarinic) – inhibit adenylyl cyclase
- G alpha q (ex. alpha-1 adrenergic)
- G beta/gamma
Name 2 bacterial toxins that can modify G protein alpha subunits
- Cholera toxin
- Pertussis toxin
Name 5 genetic conditions resulting from G protein coupled receptor mutations
TSH Receptor
- Inactivating: TSH resistance
- Activating: AD nonautoimmune hyperthyroidism, toxic adenomas
TRH Receptor
- Inactivating: Central hypothyroidism
LH Receptor
- Inactivating: Leydig cell hypoplasia (males), hypergonadotropic hypogonadism (females)
- Activating: testotoxicosis (males)
FSH Receptor
- Inactivating: AR hypergonadotropic ovarian dysgenesis or hypogonadism (females), impairment in spermatogenesis (males)
GnRH Receptor
- Inactivating: Isolated hypogonadotropic hypogonadism
GHRH Receptor
- Inactivating: Isolated GH deficiency
PTH Receptor
- Inactivating: Blomstrand’s chondrodysplasia (homozygous), enchodromatosis (heterozygous)
- Activating: Jansens metaphyseal chondrodysplasia
CaSR
- Inactivating: Familial benign hypocalciuric hypercalcemia (heterozygous), neonatal severe hyperparathyroidism (homozygous)
- Activating: AD hypocalcemic hypercalciuria
ACTH/Melanocortin-2 Receptor
- Inactivating: Familial glucocorticoid deficiency type 1
Vasopressin
- Inactivating: X linked nephrogenic DI
Where are receptors for the following steroid hormones located:
- Glucocorticoid
- Mineralocorticoid
- Androgen
- Progesterone
- Estrogen
- Thyroid hormone
- Vitamin D
- Glucocorticoid, Mineralocorticoid, Androgen, Progesterone: cytoplasmic, multimeric complexes, HSP bound
- Estrogen: nuclear compartment, HSP bound
- Thyroid hormone, Vitamin D: bound to chromatin in nucleus
List 3 genetic conditions resulting from mutations in steroid or thyroid hormone receptors
- Vitamin D-dependent rickets (type 2): vitamin D receptor
- Androgen insensitivity (complete or partial): androgen receptor
- Thyroid hormone resistance: thyroid receptor
- Pseudohypoaldosteronism: mineralocorticoid resistance
- Glucocorticoid resistance: rare, likely because it is so life-threatening
List the steps of GH receptor signaling (cytokine receptor)
- Two domains of single GH molecule bind two independent GH receptors, dimerization occurs
- Janus kinase (JAK) 2 is activated, undergoes autophosphorylation
- Tyrosine phosphorylates GH receptor and provides a docking site for signal transducer and activator of transcription (STAT)
- STATs are phosphorylated, dissociate from GH receptor, migrate to nucleus and bind DNA regulatory elements
- Transcription occurs (ex. of IGF1 gene)
List the steps in thyroid hormone function
- T3 and T4 circulate bound to thyroid binding proteins. Free hormones diffuse through cell membrane
- In cytoplasm, T4 is converted to T3 by deiodinase
- T3 moves to the nucleus and binds to thyroid receptor (TR) monomer
- Heterodimerization with RXR (retinoid X receptor) on the TRE (thyroid response element), displacement of co-repressors and binding of co-activators
- Gene transcription activation by TR-co-activator complex
List the steps in testosterone function
- Passive diffusion of testosterone into the cytoplasm and nucleus
- Binding of testosterone to ligand-binding domain on androgen receptor
- Homodimerization of receptor
- Binding of homodimer’s DNA binding domain to hormone response element (HRE)
- Transcriptional activation by activation function (AF-2) of ligand binding domain
- Diffusion of co-repressors
- Activation of co-activators –> DNA transcription
- Translation of mRNA to protein, hormone effect at target cell
Steroid hormone receptors like to form ____dimers, while thyroid hormone receptors like to form ____dimers
Steroid hormone receptors like to form HOMOdimers, while thyroid hormone receptors like to form HETEROdimers with RXR (also vitamin D receptor)
Name 6 hormones each that act via:
1) Membrane receptors
2) Intracellular/nuclear receptors
Membrane receptors:
- G protein coupled: ACTH, TSH CRH, vasopressin, LH, FSH, GnRH, TRH, GHRH, somatostatin, glucagon, oxytocin, PTH
- Cytokine: GH, prolactin, leptin
- Tyrosine kinase: insulin, IGF1, fibroblast growth factor
Intracellular/nuclear receptors:
Glucocorticoids, mineralocorticoids, thyroid hormone, vitamin D, estrogen, androgens
Name 4 hormones for which measurement by standard assays are influenced by binding proteins
- Cortisol
- Thyroid hormones (T3 and T4)
- Testosterone
- Estradiol
- IGF1 & GH
Name 2 genetic conditions resulting from GNAS1 mutatinos (G protein alpha subunit, NOT G protein coupled receptor)
- Inactivating:
- Pseudohypoparathyroidism type 1 (Albright Hereditary Osteodystrophy)
- Pseudopseudohypoparathyroidism
- Activating: McCune albright syndrome
