Hormone Action I Flashcards
1
Q
what do both protein hormones and steroid hormones absolutely require?
A
a receptor to bind to
2
Q
what is the intersection of the nervous and endocrine system?
A
the hypothalamus
3
Q
what are gonadotropins?
what to they do?
where are they produced?
A
- gonadtropins =
- LH (leutinizing hormone)
- FSH (follicle stimulating hormone)
- produced by gonadotrophes: basocophils in the adenohypophysis (ant pituitary)
4
Q
what are the respective chemical messengers that mediate the
- nervous system
- endocrine system
- immune system
A
- nervous system - neurotransmitters
- endocrine system - hormones
- immune system - cytokines
5
Q
what hormones does the thyoid gland produce?
A
follicular cells - T3 and T4
parafollicular cells - calcitonin
6
Q
what hormones does the parathyroid produce?
A
parathyroid hormone (PTH) - increases blood calcium level:
maintains blood Ca++ between 9-11 mg/dl
7
Q
what hormones does the adrenal gland produce?
A
- adrenal cortex: steroids
- zona glomerusa = aldosterone (mineralcorticoid), zona fasculata = glucocorticoid, zona reticularis = glucorticoids + androgens
- adrenal medulla: E/NE
8
Q
what hormones does the pineal gland produce?
A
pinealocytes - produce melatonin.
synchronizes sleep/wakefulness with day and night
9
Q
what hornmones do the reproductive glands produce?
A
- testes - testosterone
- ovaries - estrogen & progesterone
10
Q
what hormones does the placenta produce?
A
- human chorionic gonadotropin (HCG). production begans as soon as zygote implants in the uterus
- estrogen
- progesterone
11
Q
how long can HCG be detected after implanation?
A
- 24-48 hr in blood
- 48-72 hrs in urine
12
Q
which hormones fit into each chemical classification?
A
< 100 aas = peptide, > 100 = protein
TRH = made by hypothalamus, stimulates prolacting/TSH release
13
Q
what are the lipophillic hormones?
characterize them in terms of:
- their water solubility
- whether or not they have transport proteins
- their plasma half-life
- what kind of receptor they have
- what mediators they rely on
A
- are NOT water soluble
- include:
- steroids: aldosterone, glucocorticoids, androgens
- T3 & T4
- Vit D
14
Q
what are the hydrophillic hormones?
classify them in terms of
- their water solubility
- whether or not they have transport proteins
- their plasma half-life
- what kind of receptor they have
- what mediators they rely on
A
- water soluble
15
Q
insulin and glucagon
- are produced by what cells
- act on what target organs?
- have what major effects?
A
- insulin
- beta cells in the pancreas
- act on - liver, skeletal muscle & adipose tissue
- lower blood glucose
- glucose uptake –> glucose –> glycogen
- glucagon - increases blood glucose
- alpha cells in the pancreas
- act on - liver, adipose
- there are no glucagon receptors on muscle
- increase blood glucose
- glycogen –> glucose
16
Q
blood glucose is tightly regulated by insulin and glucagon at what at what concentration?
A
60 - 100 mg/dl
17
Q
endocrine vs paracrine vs autocrine hormones
A
- hormones are made by cells and then:
- endocrine hormones = are transported thru blood to act on distant tissue
- paracrine hormones = act on adjacent cells
- autocrine hormones = act on that same cell
18
Q
what are examples of paracrine hormones?
A
prostaglandins & leukotrienes (fatty acid derivates) - act locally in nearby tissue to induce inflammation
19
Q
what is an example of autocrine action
A
growth factor produced by in cancer cells
20
Q
receptors are
- generally what macromolecule?
- bound by what molecule?
- generally divided into what two categories & how do these categories differ functionally?
A
- generally proteins
- bound by a ligand
- two general types:
- cell-surface receptors:
- found on the plasma membrane
- bound by hydrophillic ligands (they cannot cross the phospholipid membrane)
- intracellular receptors:
- found in the cytosol (often are nuclear receptors)
- bound by lipophillic ligands (are transported thru the ECF by a carrier protein, then cross the membrane oto act internally)
- cell-surface receptors:
21
Q
what kind of receptors do aa derivates, peptide hormones, protein hormones, and steroid hormones bind?
A
- aa derivates, peptides & proteins (hydrophillic): plasma membrane receptor
- steroids (lipophillic): intracellular receptor
22
Q
hydrophillic hormones rely on what process to induce a response?
A
-
signal transduction: converts binding of ligand to plasma membrane into a intracellular response
- often mediated by the cAMP cascade (Gs - adenylate cyclase - cAMP)
23
Q
insulin binds to
- what kind of receptor?
- inducing an intracellular response through what manner? describe this process.
A
- binds to a plasma membrane receptor
- specifically, a tyrosine kinase receptor:
- an alpha-beta heterodimer associated with Tyr residue
- a subunit = purely outside
- B subunit = protrudes intracellularly, associated with Tyr
- an alpha-beta heterodimer associated with Tyr residue
- specifically, a tyrosine kinase receptor:
- induces response via signal transduction: a kinase cascade
- insulin binds to a subunit inducing a conformation change (phosphorylation at Tyr residue) B subunit, activating it.
- B itself then phosphorylates a Tyr residue on a IRS 1-4 (insulin receptor substrate) protein
- IRS 1-4 then phosphorylate & activates PI3 kinase
- PI3 kinase then phosphorylates & activates several intermediates, which
- lead to = protein translocation, enzyme activity, gene transciprtion
24
Q
the JAK-stat pathway is
- utilized by what ligands?
- involves what kind of receptors?
- facilitates an intracellular response how?
A
- ligands (all hydrophillic hormones):
- growth hormones
- prolactin
- erthropoiten
- receptor: a plasma membrane receptor made of two identical subunits with intracellular projections associated with JAK proteins
- ligands binds receptor and it dimerizes (subunits come together), which
- phosphorylates JAK proteins, which then
- phosphorylate Tyr residues of receptor intracellular projections, which
- recruit STAT proteins - and other proteins that bind thru SH2 domains - so that JAK proteins can phosphorylate them
- phoshorylated STAT proteins dimerize the enter the nucleus to activate transciption
25
proteins with _src homology 2_ are activated how?
= proteins with SH2 domains. they are activated by
1. binding a phosphorylated _intracellular domain_ of a JAK-STAT receptor
* recruited by STAT
* phosphorylated by JAK
26
GCPRs are
* what kind of receptors?
* activated how?
* induce and intracellular response by what manner?
* _plasma membrane_ receptor made of intracellular *a, B & y* subunits (*a* bound to GDP)
* activated when a ligand binds the extracellular portion:
* GDP becomes displaced from *a subunit*
* GTP binds *a subunit*
* *a subunit* dissociates from *By subunits*
* *By subunits* free to bind to an **effector** in the plasma membrane
* induce intracellular response by activating an **effector** that then activates a **secondary messenger**
27
match each GCPR family with its respective
1. effector
2. secondary messenger
Gs/Gi - cAMP
Gq - DAG & phosphatidyinositides
G12 - Ca++
28
what are the downstream effects of each GCPR's secondary messenger (cAMP, cGMP, DAG, phosphatidylinositides, Ca++)?
* Gs/Gi --\> adenylate cyclase --\> cAMP --\> PKA
* Gq --\> phospholipase C --\> DAG + phosphatidyl isonitides
* DAG --\> PKC
* phosphatidylinositides --\> Ca++ --\> calmodulin kinase
* NO or guanyl cyclase --\> cGMP --\> PKG
* G12 --\> Ca++ --\> calmodulin kinase
PKA/PKC/PKG & calmodulin kinase all lead to **phosphorylation of protein substrates**
29
cAMP
* associated with what GCPR and effector?
* has what downstream effects?
* Gs
* adenylate cyclase
* displaces **inhibitory regulatory dimer** **(R2)** from **inactive PKA** (**R2C2**) leaving active PKA - a **catalytic dimer** (**C2**)
* active PKA then phosphoryaltes proteins
30
how is the cAMP signal attenuated?
by **phosphodiesterases**, which degrade cAMP into 5-AMP
31
cGMP
* is associated with associated with what GCPR and secondary messenger?
* has what downstream effects?
* no GCPR association
* secondary messenger: **guanylyl cyclase,** of which there is a
1. _membrane form:_ activated by **ANF** (atrial natriuretic peptide)
2. _intracellular form:_ activated by **NO** (intra or extra cellular)
* guanyoloyl cyclase converts GTP to cGMP
* cGMP relaxes phosphorylates _smooth muscle proteins_ **--\> SM relaxation --\> vasodilation**
32
IP3, DAG and Ca++ are associated with what GCPR and effector?
they have what downstream effects?
* Gq
* phospholipase C
* cleaves PIP2 into DAG + IP3
* DAG activates _PKC_ --\> phosophorylate proteins
* IP3 **binds to ER** to release Ca++, which either
* exits cell
* activates _caldmodulin kinase_ --\> phsophorylates proteins
33
intracellular hormone receptors are
* bound by what types of ligands?
* divided into what two general classes? how do receptors in each class operate differently?
* bound by **lipophillic hormones** (are lipophillic hormone receptors) that were are dropped off by a _plasma protein_
* these receptors are either:
* **cytosolic receptors (Subclass I)**
* bound by
* SEX STEROIDS
* are in the cytosol bound to an _inhibitory heat shock protein_ that is displaced by ligand so that the ligand-receptor complex can enter the nucleus
* **nuclear receptors (Subclass II)**
* ****bound by
* THYROID HORMONES (thryoxine)
* RETINOIDS
* VITAMIN-D
34
what hormones act JAK-STAT proteins?
= hydrophillic hormones
* GH (from s*omatotrophes*)
* prolactin (from *lactotrophes*)
* erythropoitin cytokines
35
which hormones activate guaunylyl cyclase?
* atrial natriertic factor (ANF) - membrane bound guanylyl cyclase
* NO - intracellular guanylyl cyclase
36
which hormones activate **cytosolic receptors**?
AKA _subclass I_ lipophillic hormone receptors
SEX STEROIDS
37
which hormones activate nuclear receptors?
AKA Sublcass II lipophillic hormone receptors
* thyroid hormones
* retinoids
* vitamin D
38
what hormones activate an intracellular kinase cascade?
insulin
39
the endocrine system is tightly regulated by?
negative feedback
