Costanzo

Question 1

Describe the biosynthesis of peptide hormones

Answer 1

1. In the nucleus, the gene for the hormone into mRNA, which is then translated on ribosomes in the cytosol into preprohormones
2. Signal peptides help dock the preprohormone to the ER
3. The signal peptide is removed in the ER, coverting the preprohormone to a prohormone
4. 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
5. Secretory vesicles are translocated to the cell membrane until the cell is signaled for release

Question 2

What are the steroid hormones?

Answer 2

• cortisol
• aldosterone
• estradiol and estriol
• progesterone and testosterone
• 1,25-dihydroxycholecalciferol (Vit D)

Question 3

Steroid hormones are all derivates of what?

Answer 3

cholesterol

Question 4

What are the amine hormones?

Answer 4

catecholamines (epi, nor, and dopamine), melatonin/serotonin, and thyroid hormones

Question 5

Amine hormones are all derivates of what?

Answer 5

tyrosine

Question 6

How and when are FSH and LH released from the anterior pituitary?

Answer 6

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

Question 7

How is oxytocin involved in positive feedback?

Answer 7

Dilation of the cervix causes the posterior pituitary to secrete oxytocin. In turn, oxytocin stimulates uterine contraction, which causes further dilation of the cervix.

Question 8

What is hormonal sensitivity?

Answer 8

The hormone concentration that produces 50% of the maximal response.

Question 9

What are the major mechanisms of hormone action on target cells?

Answer 9

• adenylyl cyclase activation, with cAMP
• phsopholipase C activation, with IP3/Ca2+
• steroid hormone mechanism
• tyrosine kinase mechanism
• guanylate cyclase activation, with cGMP

Question 10

What hormones act via adenylyl cyclase activation?

Answer 10

FLAT-ChAMP

FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2 receptor), MSH, PTH

GHRH

Calcitonin

Glucagon

B1 and B2 receptors

Question 11

What hormones act via phospholipase C activation?

Answer 11

GOAT HAG

GnRH, Oxytocin, ADH (V1 receptor), TRH, Histamine, Angiotensin II, Gastrin

a1 Receptors

Question 12

What hormones act via the steroid mechanism?

Answer 12

PET CAT on TV

Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T4, T3, and Vit D

Question 13

What hormones act via the tyrosine kinase mechanism?

Answer 13

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

Question 14

What hormones act via the gyanlate cyclase mechanism?

Answer 14

ANP and NO

Question 15

Briefly describe how GCPR work

Answer 15

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).

Question 16

Adenylyl cyclase, once activated by the alpha subunit-GTP complex, converts ATP to cAMP. How is cAMP inactivated once it activated PKA?

Answer 16

Converted to inactive 5’-AMP by phosphodiesterase

Question 17

How does phospholipase C work?

Answer 17

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

Question 18

How do hormones that bind to guanylyl cyclase work?

Answer 18

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

Question 19

What do PKA and PKC do once activated?

Answer 19

They phosphorylate serine and threonine moieties on proteins that execute the hormone’s actions

Question 20

What are the types of tyrosine kinases and how do they work?

Answer 20

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)

Question 21

One type of receptor tyrosine kinase is the epidermal growth factor receptor (EGFR). How does it work?

Answer 21

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

Question 22

Another type of receptor tyrosine kinase is the insulin and IGF receptors. How do they work?

Answer 22

These are already dimerized before ligand binding, but ligand binding produces similar effects

Question 23

How do tyrosine kinase-assoicated receptors (e.g. growth hormone receptors) work?

Answer 23

They also have an extracellular and intracellular domain, but rely on associated proteins such as JAK/STAT