Hormone Action I Flashcards
what do both protein hormones and steroid hormones absolutely require?
a receptor to bind to
what is the intersection of the nervous and endocrine system?
the hypothalamus
what are gonadotropins?
what to they do?
where are they produced?
- gonadtropins =
- LH (leutinizing hormone)
- FSH (follicle stimulating hormone)
- produced by gonadotrophes: basocophils in the adenohypophysis (ant pituitary)
what are the respective chemical messengers that mediate the
- nervous system
- endocrine system
- immune system
- nervous system - neurotransmitters
- endocrine system - hormones
- immune system - cytokines
what hormones does the thyoid gland produce?
follicular cells - T3 and T4
parafollicular cells - calcitonin
what hormones does the parathyroid produce?
parathyroid hormone (PTH) - increases blood calcium level:
maintains blood Ca++ between 9-11 mg/dl
what hormones does the adrenal gland produce?
- adrenal cortex: steroids
- zona glomerusa = aldosterone (mineralcorticoid), zona fasculata = glucocorticoid, zona reticularis = glucorticoids + androgens
- adrenal medulla: E/NE
what hormones does the pineal gland produce?
pinealocytes - produce melatonin.
synchronizes sleep/wakefulness with day and night
what hornmones do the reproductive glands produce?
- testes - testosterone
- ovaries - estrogen & progesterone
what hormones does the placenta produce?
- human chorionic gonadotropin (HCG). production begans as soon as zygote implants in the uterus
- estrogen
- progesterone
how long can HCG be detected after implanation?
- 24-48 hr in blood
- 48-72 hrs in urine
which hormones fit into each chemical classification?
< 100 aas = peptide, > 100 = protein
TRH = made by hypothalamus, stimulates prolacting/TSH release
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
- are NOT water soluble
- include:
- steroids: aldosterone, glucocorticoids, androgens
- T3 & T4
- Vit D
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
- water soluble
insulin and glucagon
- are produced by what cells
- act on what target organs?
- have what major effects?
- 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
receptors are
- generally what macromolecule?
- bound by what molecule?
- generally divided into what two categories & how do these categories differ functionally?
- 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:
hydrophillic hormones rely on what process to induce a response?
-
signal transduction: converts binding of ligand to plasma membrane into a intracellular response
- often mediated by the cAMP cascade (Gs - adenylate cyclase - cAMP)
insulin binds to
- what kind of receptor?
- inducing an intracellular response through what manner? describe this process.
- 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
the JAK-stat pathway is
- utilized by what ligands?
- involves what kind of receptors?
- facilitates an intracellular response how?
- 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
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
match each GCPR family with its respective
- effector
- secondary messenger
Gs/Gi - cAMP
Gq - DAG & phosphatidyinositides
G12 - Ca++
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
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
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
- membrane form: activated by ANF (atrial natriuretic peptide)
- intracellular form: activated by NO (intra or extra cellular)
- guanyoloyl cyclase converts GTP to cGMP
- cGMP relaxes phosphorylates smooth muscle proteins –> SM relaxation –> vasodilation
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
- cleaves PIP2 into DAG + IP3
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
- bound by
-
nuclear receptors (Subclass II)
-
bound by
- THYROID HORMONES (thryoxine)
- RETINOIDS
- VITAMIN-D
-
bound by
-
cytosolic receptors (Subclass I)
