144-hormone mechanisms Flashcards
three basic features of ligands for nuclear receptors
small lipophilic, not directly encoded by genome
what are the two major features of all nuclear receptor structures
a dna binding domain and a ligand binding/dimerization domain (in addition to the other four domains)
5 classes of nuclear receptors
- Classical- activated by thyroid or steroid
- Vitamin-
- Metabolic intermediates and Products- fatty acids, bile acids, oxysterols
- Xenobiotic- induce CYPs
- Orphan- ??
most nuclear receptors act as a ____ by ____ with ____ receptors
dimer, binding, similar or different
three examples of nuclear receptor disease
thyroid hormone resistance, androgen insensitivity, hereditary vit d resistant rickets
Receptro Tyrosin Kinases: where is most of the variation? Most need to act as___ and are activated by intracellular___
extracellular domain
dimers (homo- or hetero-)
phosphorylation
Multiple Endocrine Neopasia (MEN): what mutation?
Ret tyrosine kinase receptor enhanced dimerization and GOF.
MEN 2A vs 2B
2A (extracellular domain mutation): parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma
2B (intracellular domain mutation): mucosal neuromas, Marfanoid body habitus, medullary thyroid carcinoma, pheochromocytoma
How do Cytokine receptors work?
form dimers, cytokine binds, JAK proteins phsophorylate other proteins which go into nucleus to affect transcription
Leptin receptor mutations: example of what kind of receptor? what happens?
cytokine. inactivates so you stay hungry and get early obesity
GPCRs: what are they coupled to intracellularly? How can they be regulated?
Heterotrimeric (alpha, beta, gamma) proteins.
Hesensitized and downregulated (endocytosis/degradation)
Diabetes insipidus: how do you differentiate the two kinds? which is due to GPCR mutation and how?
measure urine osmolality while depriving of water then administering vasopressin. Partial will respond to H2O deprivation and central will respond to vasopressin.
Nephrogenic. Don’t get aquaporins inserted in membrane
Grave’s Disease: what happens
antibodies for tsh GPCR which activate it. Low TSH with high thyroid hormone
Peptide hormone synthesis: insulin example. what helps sort the peptides? then what happens? what can be measured?
amino-terminal “tag” which gets cleaved. Leaves A, B, C chains. C gets cleaved and secreted with A and B chains. C can be used as indicator of insulin secretion
Addisons: what is the peptide? what happens?
POMC (propeptide for ACTH). as it gets cleaved it gives off active hormone byproducts
