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

EXAM 2: Lecture 11,12 Flashcards

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
Q

convertase 2

vertebrates

A

makes alphaMSH and beta-endorphin in pars intermedia

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26
Q

evolution of POMC

A

ancestral gene has the gamma, alpha, and beta MSH

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27
Q

melanocortins

A

vertebrates only; absent in primative verebrates

hormones (POMC)
5 receptors (MCR1-5)
melanocortin receptor accessory proteins (MRAP1-2)

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28
Q

melanocortin antagonists

A

agouti signaling protein (ASP)

agouti-related protein (ARP)

beta-defensin 103 binds to MCR1

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29
Q

melanocortins function

A

regulation of

  • pigmentation
  • appetite
  • glucocorticoid secretion
  • exocrine secretion (GOF)
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30
Q

MCR receptor and POMC co-evolved

A

ya

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31
Q

MCR

A

melanocortin receptor is comprised of a complex family of 5 members

GPCR/cAMP/PKa

differential ability for POMC products

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32
Q

MCR1

A

alphaMSH, betaMSH, ACTH > gammaMSH

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33
Q

MCR2

A

ACTH only

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34
Q

MCR3

A

alphaMSH, betaMSH, ACTH, gammaMSH

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35
Q

MCR4

A

alphaMSH, betaMSH, ACTH > gammaMSH

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36
Q

MCR5

A

alphaMSH > betaMSH=ACTH > gammaMSH

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37
Q

MCR1 antagonists and expression

A

agouti

melanocytes, leukocytes

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38
Q

MCR1 function

A

pigmentation/inflammation

UV protection

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39
Q

MCR2 expression

A

adrenal cortex

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40
Q

MCR2 function

A

steroidogenesis

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41
Q

MCR3 antagonists and expression

A

agouti, AgRP

CNS/GI/Renal
arcuate nucleus

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42
Q

MCR3 function

A

energy balance, feeding

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43
Q

MCR4 antagonists and expression

A

agouti, AgRP

CNS; PVN of hypothalamus

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44
Q

MCR4 function

A

energy balance, feeding

45
Q

MCR5 expression

A

exocrine

46
Q

MCR5 function

A

gland secretion

47
Q

ACTH + MCR2

A

binds to surface of adrenal gland cells

cAMP/PKA stimulates rapid translocation of cholesterol across inner mitochondrial membraine

steroidogenesis

48
Q

MRAP

A

gene encodes a single TMS protein unique from other reported GPCR Aps

essential for MCR trafficking to cell surface

49
Q

TRH

A

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
Q

TSH

A

glycoprotein secreted in response to TRH
targets thyroid cells

thyroxine – T3/T4

dimer protein

51
Q

TSH alpha subunit

A

shared with hCG, LH, and FSH

stimulates AC

10 conserved cysteines
5 S-S bridges
92-96 AA

52
Q

TSH beta subunit

A

specific for TSH receptor

12 conserved cysteines
6 S-S bridges
105-150 AA

53
Q

TSH alpha/beta

A

completely dissociated because kd is larger

subunits have negative specificity at receptor

54
Q

TSh negative specificity

A

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
Q

evolution of TSH

A

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
Q

TSH release

A

under differential control of TRH and VIP

coincidence control

novel addition of receptor neg specificity; another level of control

57
Q

TSH effects at the thyroid

A

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
Q

thyroxine

A

steroid-like hormone binding to nuclear receptor

regulates gene transcription and growth and development of all verts

59
Q

thyroxine is the only iodine containing molecule in animals

A

iodine is more common in ocean than on land

- found in jellyfish

60
Q

protochordates and iodine

A

produced in endostyle (no HPA), associated with pharynx

61
Q

lamprey and iodine

A

high concentrations prevent metamorphosis, low concentrations = formation of adults

62
Q

thyroxine in absence of T3

A

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
Q

thyroxine receptor

A

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
Q

alpha1 thyroxine receptor

A

widely expressed

heart/skeletal muscle

newborns

65
Q

alpha2 thyroxine receptor

A

widely expressed

doesn’t bind T3

66
Q

beta1 thyroxine receptor

A

CNS, liver, kidney

brain during childhood

67
Q

beta2 thyroxine receptor

A

HPA

68
Q

thyroxine transport

A

T3 binding proteins have low to high affinity for T3 and affinity is related to availability of iodine

69
Q

T3 binding proteins

A

albumin

transthyretin

thyroxine binding globulin (TBG)

70
Q

albumin

A

fish, amphibians, reptiles, monotremes, marsupials, mammals, birds

71
Q

transthyretin

A

mammals, birds, fish

72
Q

TBG

A

mammals only

73
Q

affinity of T3 binding proteins

A

albumin < transthyretin < TBG

74
Q

ocean T3

A

abundant iodine, animals express and use albumin

75
Q

amphibians T3

A

less abundant iodine, animals use transthryretin and albumin

76
Q

terrestrial T3

A

less iodine, animals express all 3

store 3-6 months of thyroxine in the body

77
Q

herbivores T3

A

have long GI tract, increasing potential loss of T3 in feces; express all 3 binding proteins

78
Q

carnivores T3

A

shorter GI tract, decreasing loss of T3 in feces; express albumin and transthyretin

79
Q

CNS T3

A

T3 needed for normal CNS development so vertebrate CNS expresses TBG to pull T3 out of blood into the CNS

80
Q

secretin gene family

A 
GHRH
PACAP
glucagon
secretin
VIP
PHM
PHL
GIP
glucagon-like peptide
81
Q

secretin gene family evolution

A

present before verts

produced in HPA and peripheral tissues
gut pancreas ovary testes

82
Q

PACAP

A

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
Q

PACAP evolution

A

ancestral form of regulation

97% conserved in verts

84
Q

PACAP receptors

A

GPCRs

VPAC1 and VPAC2

PAC1

huge range of effects

85
Q

PACAP receptors:

VPAC1 and VPAC2

A

bind PACAP, VIP, PRP with same affinity

share 55% sequence homology and differentially expressed in tissues

86
Q

PACAP receptors:

PAC1

A

20 isoforms with developmentally related expression patterns

87
Q

GHRH

A

sequence is variable

GHRH and C-peptide

verts and inverts

88
Q

GHRH and PACAP distribution:

mammals

A

GHRH neurons in arcuate and dorsomedial hypothalamic nuclei

PACAP neurons throughout brain

89
Q

GHRH and PACAP distribution:

amphibians

A

GHRH neurons in preoptic nucleus

PACAP neurons throughout brain

90
Q

GHRH and PACAP distribution:

fish

A

GHRH/PACAP neurons widely in CNS

91
Q

GHRH/PACAP/Ghrelin

A

act through GPCR

inc. cAMP
GH release

92
Q

somatostatin inhibits

A

adenylate cyclase

93
Q

human GHRH vs invertebrate APRP

A

invertebrates have 50% sequence homology

not a hormone but suggests a common ancestor - 3 gene duplication events

94
Q

secretin

A

water balance, GI movement (verts)

  • inhibition of stomach acid secretion, stimulating pancreatic bicarbonate secretion
  • stimulation of bile production
95
Q

secretin info

A

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
Q

glucagon

A

hyperglycemic agent via gluconeogensis and glycogenolysis

dec. FFA synthesis in adipose

97
Q

glucagon in verts

A

alpha cells of pancreas

GPCR, alphaS, cAMP

98
Q

GIP

A

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
Q

VIP

A

vasoactive intestinal peptide

stimualtes heart contraction, vasodilation, glycogenolysis, hypotensive, tracheal vasodilation

100
Q

VIP info

A

28 AA, GPCR, alphaS, cAMP

gut, pancreas, hypothalamus (production sites)

101
Q

PACAP family evolution

A

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
Q

genes for PACAP family

A

1: PACAP/PRP
2: VIP/PHM/PHI
3: GCG/GnRH/secretin/GIP

all receptors are GPCR – coevolution

103
Q

GH / prolactin /somatolactin

A

gene family with large class1 helical cytokines

share 25-30% sequence homology

4 conserved cysteines with 2 S-S bonds

no invert forms

104
Q

GH

A

21-24 kDa

stimulation of growth and metabolism of muscle, bone, cartilage

105
Q

Prolactin

A

22-25 kDa

300 physio actions centered on osmoregulation and milk production

106
Q

Somatolactin

A

22-23 kDa

teleost fish only, control of energy balance, sexual maturation, skin coloration

107
Q

GHRH stimulates

A

release of GH

108
Q

GH control

A

GHRH controls GH and IGF release

additional hormonal level of control at pituitary with SS

Comparative Endocrinology (4 decks)

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