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Comparative Endocrinology > EXAM 2: Lecture 11,12 > Flashcards

EXAM 2: Lecture 11,12 Flashcards

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1
Q

urotensin

A

sauvagine, Ucn1

strongest known vasoconstrictor

affects cardiovascular, nervous, endocrine, renal systems

discovered in fish; fish osmoregulation

GPCR –> PKc activation

appetite control

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2
Q

Ucn2/3

A

not active in all vertebrates

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3
Q

Ucn2/3: vertebrates

A

binds to urotensin GPCR, behaves like epi/norepi

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4
Q

Ucn2/3: invertebrates

A

CNS, satiety, feeding behavior

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5
Q

three main families of diuretic hormones in insects

A

CRH-family

calcitonin-like peptides

kinin family

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6
Q

DH

A

increases cAMP production in malpighian tubules, stimulating K+/Na+ transport

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7
Q

CRH-ACTH

A

7 discriminator pathway collecting information at the hypothalamus and pituitary

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8
Q

ACTH

A

part of an unusual gene structure

proopiomelanocortin (POMC); another level of control

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9
Q

CRH-ACTH info

A

peptide

composed of

  • proenkephalin (PENK)
  • prodynorphin (PDYN)
  • POMC
  • pronociceptin (PNOC)

peptides share the YGGF core opioid sequence or FGGF PNOC core sequence

absent in inverts

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10
Q

O/O family

A

conserved cysteines at N-term in addition to core motifs

PENK, PDYN, PNOC – 6 conserved cysteines
POMC - 4 conserved

absent in rudimentary vertebrates: amphioxus and tunicates

all four genes found in same chromosomes

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11
Q

synteny

A

all genes found on same chromosomes

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12
Q

proenkephalin

A

proteolytically processed to met and leu-enkephalins

natural opioids

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13
Q

PDYN

A

expressed in uterus and CNS

building block for endorphins: pain, memory, emotional bonds

gene related to speciation from primates

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14
Q

nociceptin / orphanin (PNOC)

A

17 AA neuropeptide

natural ligand for nociceptin receptor

digested into nociceptin, nocistatin, nocil

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15
Q

nocistatin / nocil

A

blocks nociceptin signaling

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16
Q

preopiomelanocortin (POMC)

A

tissue expression of protesases, determines what hormones are released

hormones bind to GPCR known as MCR

coevolved with hormones

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17
Q

MCR

A

melanocortin receptor

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18
Q

POMC coevolved with hormones:

tetrapods

A

N-term of POMC has gammaMSH

N term of ACTH has alphaMSH

betaMSH - inside beta-lipotropin

C term portion has beta-endorphin

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19
Q

POMC: tissues have differential distribution of convertases

A

convertase 1

convertase 2

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20
Q

convertase 1

tetrapods

A

gamma MSH, ACTH, beta-lipotropin

anterior pituitary

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21
Q

convertase 2

tetrapods

A

alpha MSH, beta-endorphin

pars intermedia

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22
Q

POMC coevolved with hormones:

vertebrates

A

N term gammaMSH, central ACTH, c-term lipotropin

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23
Q

vertebrate POMC

A

each domain has core sequence of HFRW that defines melanocortin

N-term gammaMSh has gammaMSH

ACTH has alphaMSH

lipotropin has betaMSH

prohormone convertase 1
convertase II

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24
Q

prohormone convertase 1

vertebrates

A

generates ACTH/LPH in pituitary

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25
convertase 2 vertebrates
makes alphaMSH and beta-endorphin in pars intermedia
26
evolution of POMC
ancestral gene has the gamma, alpha, and beta MSH
27
melanocortins
vertebrates only; absent in primative verebrates hormones (POMC) 5 receptors (MCR1-5) melanocortin receptor accessory proteins (MRAP1-2)
28
melanocortin antagonists
agouti signaling protein (ASP) agouti-related protein (ARP) beta-defensin 103 binds to MCR1
29
melanocortins function
regulation of - pigmentation - appetite - glucocorticoid secretion - exocrine secretion (GOF)
30
MCR receptor and POMC co-evolved
ya
31
MCR
melanocortin receptor is comprised of a complex family of 5 members GPCR/cAMP/PKa differential ability for POMC products
32
MCR1
alphaMSH, betaMSH, ACTH > gammaMSH
33
MCR2
ACTH only
34
MCR3
alphaMSH, betaMSH, ACTH, gammaMSH
35
MCR4
alphaMSH, betaMSH, ACTH > gammaMSH
36
MCR5
alphaMSH > betaMSH=ACTH > gammaMSH
37
MCR1 antagonists and expression
agouti melanocytes, leukocytes
38
MCR1 function
pigmentation/inflammation UV protection
39
MCR2 expression
adrenal cortex
40
MCR2 function
steroidogenesis
41
MCR3 antagonists and expression
agouti, AgRP CNS/GI/Renal arcuate nucleus
42
MCR3 function
energy balance, feeding
43
MCR4 antagonists and expression
agouti, AgRP CNS; PVN of hypothalamus
44
MCR4 function
energy balance, feeding
45
MCR5 expression
exocrine
46
MCR5 function
gland secretion
47
ACTH + MCR2
binds to surface of adrenal gland cells cAMP/PKA stimulates rapid translocation of cholesterol across inner mitochondrial membraine steroidogenesis
48
MRAP
gene encodes a single TMS protein unique from other reported GPCR Aps essential for MCR trafficking to cell surface
49
TRH
targets anterior pituitary; released in GI tract and pancreatic islets - GPCR/PLc/IP3 pGHPa fully conserved; precursor has 5-8 copies of TRH 242 AA precursor with 6 copies of Gln-His-Pro-Gly flanked by Lys-Arg/Arg-Arg after cleavage: C terminal Gly is amidated and N term Gln into pyroGlutamate
50
TSH
glycoprotein secreted in response to TRH targets thyroid cells thyroxine -- T3/T4 dimer protein
51
TSH alpha subunit
shared with hCG, LH, and FSH stimulates AC 10 conserved cysteines 5 S-S bridges 92-96 AA
52
TSH beta subunit
specific for TSH receptor 12 conserved cysteines 6 S-S bridges 105-150 AA
53
TSH alpha/beta
completely dissociated because kd is larger subunits have negative specificity at receptor
54
TSh negative specificity
alpha subunit has high receptor affinity, beta has lower beta prevents alpha from activating wrong receptor alpha/beta subunits assemble at receptor LEVEL OF CONTROAL
55
evolution of TSH
cysteine-knot GF superfamily FSH, LH, hCG and TSH only in vertebrates alpha and beta subunits in inverts - GPA2 and GPB5 are ancestors of vert hormones all verts have thyroid TSH production occurs in other cells besides pituitary 20-54% of mass is CHOs, indispensable for full activity
56
TSH release
under differential control of TRH and VIP coincidence control novel addition of receptor neg specificity; another level of control
57
TSH effects at the thyroid
upregulation of Na+/I- symporter follicle cells; increases iodine concentration iodination of thyroglobulin conjugation of iodinated tyrosine residues movement of thyroglobulin/T3 into follicular cell proteolysis of TG and release of T3/T4 secretion of T3/T4
58
thyroxine
steroid-like hormone binding to nuclear receptor regulates gene transcription and growth and development of all verts
59
thyroxine is the only iodine containing molecule in animals
iodine is more common in ocean than on land | - found in jellyfish
60
protochordates and iodine
produced in endostyle (no HPA), associated with pharynx
61
lamprey and iodine
high concentrations prevent metamorphosis, low concentrations = formation of adults
62
thyroxine in absence of T3
receptor is bound to co-repressor proteins bound to HRE in a transcriptionally inactive state T3 bound to receptor induces conf. change that displaces co-repressor proteins co-activator proteins bind to receptor recruits RNA pol II, transcription of mRNA
63
thyroxine receptor
4 versions give same hormone ability to have widely different effects in tissues/cells genes alternatively spliced; isoforms differentially expressed in tissues and by developmental stage
64
alpha1 thyroxine receptor
widely expressed heart/skeletal muscle newborns
65
alpha2 thyroxine receptor
widely expressed doesn't bind T3
66
beta1 thyroxine receptor
CNS, liver, kidney brain during childhood
67
beta2 thyroxine receptor
HPA
68
thyroxine transport
T3 binding proteins have low to high affinity for T3 and affinity is related to availability of iodine
69
T3 binding proteins
albumin transthyretin thyroxine binding globulin (TBG)
70
albumin
fish, amphibians, reptiles, monotremes, marsupials, mammals, birds
71
transthyretin
mammals, birds, fish
72
TBG
mammals only
73
affinity of T3 binding proteins
albumin < transthyretin < TBG
74
ocean T3
abundant iodine, animals express and use albumin
75
amphibians T3
less abundant iodine, animals use transthryretin and albumin
76
terrestrial T3
less iodine, animals express all 3 store 3-6 months of thyroxine in the body
77
herbivores T3
have long GI tract, increasing potential loss of T3 in feces; express all 3 binding proteins
78
carnivores T3
shorter GI tract, decreasing loss of T3 in feces; express albumin and transthyretin
79
CNS T3
T3 needed for normal CNS development so vertebrate CNS expresses TBG to pull T3 out of blood into the CNS
80
secretin gene family
``` GHRH PACAP glucagon secretin VIP PHM PHL GIP glucagon-like peptide ```
81
secretin gene family evolution
present before verts produced in HPA and peripheral tissues gut pancreas ovary testes
82
PACAP
pituitary AC activating peptide high concentration of basic charges high charge density PACAP circulates complexed to ceruloplasmin: cu containing protein concentrations are lower than peptide hormones
83
PACAP evolution
ancestral form of regulation 97% conserved in verts
84
PACAP receptors
GPCRs VPAC1 and VPAC2 PAC1 huge range of effects
85
PACAP receptors: VPAC1 and VPAC2
bind PACAP, VIP, PRP with same affinity share 55% sequence homology and differentially expressed in tissues
86
PACAP receptors: PAC1
20 isoforms with developmentally related expression patterns
87
GHRH
sequence is variable GHRH and C-peptide verts and inverts
88
GHRH and PACAP distribution: mammals
GHRH neurons in arcuate and dorsomedial hypothalamic nuclei PACAP neurons throughout brain
89
GHRH and PACAP distribution: amphibians
GHRH neurons in preoptic nucleus PACAP neurons throughout brain
90
GHRH and PACAP distribution: fish
GHRH/PACAP neurons widely in CNS
91
GHRH/PACAP/Ghrelin
act through GPCR inc. cAMP GH release
92
somatostatin inhibits
adenylate cyclase
93
human GHRH vs invertebrate APRP
invertebrates have 50% sequence homology not a hormone but suggests a common ancestor - 3 gene duplication events
94
secretin
water balance, GI movement (verts) - inhibition of stomach acid secretion, stimulating pancreatic bicarbonate secretion - stimulation of bile production
95
secretin info
27 AA peptide 120 AA precursor: signal peptide, spacer, secretin, C-term peptide 50% identical to glucagon 25% identical to VIP 35% in GIP
96
glucagon
hyperglycemic agent via gluconeogensis and glycogenolysis dec. FFA synthesis in adipose
97
glucagon in verts
alpha cells of pancreas GPCR, alphaS, cAMP
98
GIP
gastric inhibitory peptide/ glucose-dependent insulinotropic peptide - weak inhibition of stomach acid - strong stimulator of insulin secretion due to presence of glucose in small intestine tropic hormone of pancreatic alpha cells GPCR, alphaS, cAMP
99
VIP
vasoactive intestinal peptide stimualtes heart contraction, vasodilation, glycogenolysis, hypotensive, tracheal vasodilation
100
VIP info
28 AA, GPCR, alphaS, cAMP gut, pancreas, hypothalamus (production sites)
101
PACAP family evolution
ancestral gene predates animals - genetic drift - same receptor and same signaling pathway (GPCR, alphaS) - GOF not all hormones have recognized receptors; several share same one three encoded by single gene
102
genes for PACAP family
1: PACAP/PRP 2: VIP/PHM/PHI 3: GCG/GnRH/secretin/GIP all receptors are GPCR -- coevolution
103
GH / prolactin /somatolactin
gene family with large class1 helical cytokines share 25-30% sequence homology 4 conserved cysteines with 2 S-S bonds no invert forms
104
GH
21-24 kDa stimulation of growth and metabolism of muscle, bone, cartilage
105
Prolactin
22-25 kDa 300 physio actions centered on osmoregulation and milk production
106
Somatolactin
22-23 kDa teleost fish only, control of energy balance, sexual maturation, skin coloration
107
GHRH stimulates
release of GH
108
GH control
GHRH controls GH and IGF release additional hormonal level of control at pituitary with SS

Comparative Endocrinology (4 decks)

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