-
endocrine
into circ to act on distant cells
-
paracrine
NOT into circ, local, on neighboring cells
-
autocrine
act on cells that sec them
-
juxtacrine
NOT sec, inserted into mem
-
neuroendocrine
nt sec by neurons into circ
-
glucagon rec
binds rec AND signal transduction (phosph LPK)
-
EC50
ligand conc for 1/2 max response
-
KD
ligand conc for 1/2 max occupancy of rec
-
R0, Bmax
max binding rec capcacity
-
scatchard plot
bound to free ratio hormone vs bound hormone
-
G(alpha)s
- B adrenergic amines, glucagon, PTH
- downstream: AC
-
G(alpha)i
- Ach, alpha adrenergic amines, nt
- downstream: inhib AC
-
G(alpha)q
- Ach, alpha adrenergic amines, nt
- downstream: IP3, Ca (...PLC beta)
-
G(alpha)t
- photons
- downstream: stim cGMP phosphodiesterase (breaks down cGMP)
-
G(alpha)13
- thrombin
- downstream: Na/H exchange
-
PLC beta
- PIP2 into IP3 and DAG
- Ca + DAG: stim PKC
- Ca: stim calmodulin dep prot kinase
-
ADP ribosylate G(alpha)s
cholera; always on in gut...AC, cAMP, diarrhea
-
ADP ribosylate G(alpha)i
pertussis toxin; in airways, AC..cAMP stim
-
intrinsic rec tyr kinases
insulin rec, GF rec, EGF rec
-
SH2 domain prot
Grb-2, PLC-gamma, PI3K
-
DAG analogs
tumor suppressors, phorbolesters
-
PDK1
phosph/act PKB, act via PIP3 (from PI3K)
-
PKB
phosph/inact BAD, prevent cell death
-
non-intrinsic rec tyr kinases
cytokine rec, GH rec, PRL rec
-
guanylate cyclase rec
natriueretic pep rec, ligand gated ion channels
-
-
-
CRH
- ACTH
- adrenal cortex (cortisol)
-
GnRH
- LH, FSH
- gonads (estrogen, androgen)
-
JAK
tyr kinase, GH signal transduction
-
STAT
phosph by GH rec, bind DNA seq encoding IGF-1
-
SHC, IRS-1
phosph by act tyr rec beta subunit
-
IRS-1P
act PI3K (via P110 and P85)
-
-
Akt
act p70 and pp1 (gluc metab stim)
-
-
-
-
-
-
ALS, MD, sarcopenia
neuromuscular degenerative diseases
-
PTH rx
for osetopenia, osteoporosis, bone fracture repair
-
HMG CoA reductase
committed step in stage 1 chol biosynth
-
3-isopentenyl pyrophosphate
building block for vit K2, Q10, farnesyl/geranylgeranyl attachment
-
SREBP
controls HMGCoA red synth
-
dietary chol and mevalonate
inhib HMGCoA red transL
-
AMP-act protein kinase
phosph HMGCoA reductase...inhib
-
7 alpha hydroxylase
RLS bile salt synth
-
cholyl CoA
act intermed in bile salt synth; goes to glycocholate and taurocholate
-
microsomal P450 mixed func monoxidases
hydroxylations in bile salt synth
-
LCAT
lecithin chol acyl transferase; makes chol esters, in HDL in plasma
-
ACAT
acyl CoA chol acyltransferase; VLDL synth
-
Apoprot B-100
on LDL, clathrin coated pit
-
unesterified chol
mem biosynth, sterol synth, reesterified via ACAT for storage
-
LDL structure
- cysteine rich domain
- 3 domains homol to EGF
- 6 repeats similar to blades of transducin beta
- rich in Ser an Thr w/ o-linked oligos
- phobic, transmem
- cytoplasmic
-
pro-opiomelanocortin (POMC)
ACTH precursor
-
POMC also makes...
ACTH, beta lipoprot, alpha MSH, CLIP, gamma lipotropin, beta endorphin, beta MSH, met-enkephalin
-
ACTH promotes
- chol release from chol esters (storage form)
- chol transport into mit
- chol side chain cleavage into pregnenolone
-
-
normal serum cortisol
50nmol/L at 12am
-
normal urine cortisol
250nmol/day
-
Cushinoid
cushing's syndrome due to therapy w/ glucocorticoids
-
Cushing's disease
cushing's syndrome due to tumor that inc ACTH
-
primary addison's disease
- autoimmune destruction cortex
- impaired adrenal formation
- def ACTH rec
- def steroidogenesis
-
secondary addison's disease
dec ACTH
-
-
cushing's rx
surgical ablation tumor
-
familial glucocorticoid reistance
inc serum cortisol but no hyperglucocorticoid response, mut rec w/ low aff
-
17 alpha hydroxylase
rER, pregnenolone to 17 alpha hydroxyprenenolone
-
17,20 desmolase
17 alpha hydroxypregnenolone to dehydroepiandrosterone
-
21 hydroxylase
- rER
- progesterone to 11 deoxycorticosterone
- 17alphahydroxyprogesterone to 11 deoxycortisol
-
11 beta hydroxylase
- mit
- 11deoxycorticosterone to corticosterone
- 11 deoxycortisol to cortisol
-
17 hydroxylase def
- precocious pub (male)
- masculine (female)
- salt wasting, dehydration
- dec cortisol....too much ACTH and DHEA
-
17hydroxylase/17,20 desmolase def
- dec cortisol...dec renin hypertension
- feminine (male)
- no menstruation, 2 wrong (female)
-
11 beta hydroxylase def
biphasic effects on salt and water retention
-
ADH rec
Gq..Ca...PKC/Ca cal dep kinase...sm mm contraction in vessels (VD)
-
primary DI
inc urine V (not sugary)..dec ADH
-
hereditary nephrogenic DI
mut ADH rec, hormone resistant
-
SIADH
inc ADH via tumor; dilutional hyponatremia
-
-
atriopeptinogen
- from atrial cardiocytes
- converted into atripeptin (circ form)
-
ateriosclerosis
hardening of arteries (Ca deposition in walls)
-
atherosclerosis
- build up fatty deposits in arteries
- CHF, stroke
-
statins
- HMGCoA red inhib
- lovastatin
- inc LDL rec, dec amt HMGCoA red made in hepatocytes
-
Niacin
dec TG synth via inhib synth FA, inhib VLDL synth
-
cholestyramine
- (+) polymer to inhib reabs bile (-)
- promote excretion bile (more bile salt synth, more LDL liver uptake)
-
fibric acid
- gemfibrozil, lopid
- inhib VLDL sec
-
gallstones
chol: bile salt >1, unsol chol crystallizes
-
ER enz in cortical hormone synth
- 21 hydroxylase
- 17 alpha hydroxylase
-
mit enz in cortical hormone synth
- 11 beta hydroxylase
- 18 hydroxylase
-
conjugation salts
glucouronide and sulfates
-
steroid hormone rec
located inside cell
-
A/B domain steroid hormone rec
variable, immunogenic
-
C domain steroid hormone rec
DNA binding...zinc fingers
-
D domain steroid hormone rec
hinge, transC modification
-
E domain steroid hormone rec
steroid binding, HS prot binding
-
F domain steroid hormone rec
HSP act domain
-
androgen reistance syndrome
- def DHT
- normal urogenital, female ext genitalia
-
rec + testosterone
reg sec of LH in male sex differentiation, spermatogenesis
-
rec + DHT
dev male external genitalia, prostate
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