Costanzo Flashcards
Describe the biosynthesis of peptide hormones
- In the nucleus, the gene for the hormone into mRNA, which is then translated on ribosomes in the cytosol into preprohormones
- Signal peptides help dock the preprohormone to the ER
- The signal peptide is removed in the ER, coverting the preprohormone to a prohormone
- The prohormone is transferred to the Golgi where it is packaged into secretory vesicles where proteolytic enzymes cleave peptide sequences from the prohormone to produce the final hormone
- Secretory vesicles are translocated to the cell membrane until the cell is signaled for release
What are the steroid hormones?
- cortisol
- aldosterone
- estradiol and estriol
- progesterone and testosterone
- 1,25-dihydroxycholecalciferol (Vit D)
Steroid hormones are all derivates of what?
cholesterol
What are the amine hormones?
catecholamines (epi, nor, and dopamine), melatonin/serotonin, and thyroid hormones
Amine hormones are all derivates of what?
tyrosine
How and when are FSH and LH released from the anterior pituitary?
During the folliculr phase of the menstrual cycle, the ovaries secrete estrogen, which acts on the anterior pituitary to produce a rapid burst of FSH and LH secretion. FSH and LH then not only cause ovulation, but also stimulates more estrogen release
This is an example of positive feedback
How is oxytocin involved in positive feedback?
Dilation of the cervix causes the posterior pituitary to secrete oxytocin. In turn, oxytocin stimulates uterine contraction, which causes further dilation of the cervix.
What is hormonal sensitivity?
The hormone concentration that produces 50% of the maximal response.
What are the major mechanisms of hormone action on target cells?
- adenylyl cyclase activation, with cAMP
- phsopholipase C activation, with IP3/Ca2+
- steroid hormone mechanism
- tyrosine kinase mechanism
- guanylate cyclase activation, with cGMP
What hormones act via adenylyl cyclase activation?
FLAT-ChAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2 receptor), MSH, PTH
GHRH
Calcitonin
Glucagon
B1 and B2 receptors
What hormones act via phospholipase C activation?
GOAT HAG
GnRH, Oxytocin, ADH (V1 receptor), TRH, Histamine, Angiotensin II, Gastrin
a1 Receptors
What hormones act via the steroid mechanism?
PET CAT on TV
Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T4, T3, and Vit D
What hormones act via the tyrosine kinase mechanism?
Receptor (MAP Kinase): Insulin, IGF-1, FGF, PDGF, EGF
Receptor-associated (JAK/STAT): PIGGlET; Prolactin, Immunomodulators (IL-2, IL-6, IFN, etc), GH, G-CSF, EPO, TPO
What hormones act via the gyanlate cyclase mechanism?
ANP and NO
Briefly describe how GCPR work
G-proteins are attached to the receptor and trimeric enzymes consisting of alpha, beta, and gamma subunits. The alpha subunit, when quiescent, is bound to GDP and is inactive. Binding of an appropriate ligand stimulates binding of the alpha subunit to GTP, causing it to dissociate from the G-protein and the beta/gamma subunits to either bind to adenylyl cyclase (if bound to Gs or Gi) or phospholipase C (if bound to Gq).
Adenylyl cyclase, once activated by the alpha subunit-GTP complex, converts ATP to cAMP. How is cAMP inactivated once it activated PKA?
Converted to inactive 5’-AMP by phosphodiesterase
How does phospholipase C work?
If the G-protein is Aq-subunit bound, the alphaq subunit activates phospholipase C, which then catalyzes the liberation of diacylglycerol and IP3 from PIP2. IP3 causes the release of Ca2+ from intracellular stores in the ER which then activates PKC
How do hormones that bind to guanylyl cyclase work?
ANP works through a receptor guanylyl cyclase mechanism- the extracellular domain of the receptor has a binding site for these hormones, while the intracellular domain has guanylyl cyclase activtiy, which converts GTP tocGMP
NO on the other hand works through a cytosolic guanylyl cyclase- NO is synthesized in vascular endothelial cells from NO synthase and diffuses into nearby vascular smooth muscle cells where it binds to and activates soluble, cytosolic guanylyl cyclase
What do PKA and PKC do once activated?
They phosphorylate serine and threonine moieties on proteins that execute the hormone’s actions
What are the types of tyrosine kinases and how do they work?
Receptor tyrosine kinases have intrinsic tyrosine kinase activity while tyrosine kinase-associated receptors (insulin) only associate noncovelantly with proteins that have tyrosine kinase activity to phosphorylate tyrosine moieties (GH)
One type of receptor tyrosine kinase is the epidermal growth factor receptor (EGFR). How does it work?
It is a monomeric type, that upon ligand binding, dimerizes to activate the intrinsic tyrosine kianse, and phosphorylate tyrosine moieties on itself and other proteins, leading to effect
Another type of receptor tyrosine kinase is the insulin and IGF receptors. How do they work?
These are already dimerized before ligand binding, but ligand binding produces similar effects
How do tyrosine kinase-assoicated receptors (e.g. growth hormone receptors) work?
They also have an extracellular and intracellular domain, but rely on associated proteins such as JAK/STAT
