Lecture 7 Midterm 1 Flashcards
1
Q
what is the function of thyrotropin-releasing hormone (TRH)
A
regulation of thyroid stimulating hormone
2
Q
what is the function of gonadotropin-releasing hormone
A
- (main) regulation of luteinizing hormone and follicle stimulating hormone from ant. pit
- limbic system (emotion) neuromodulator
- placenta and ovaries make GnRH - acts locally
3
Q
somatostatin function
A
inhibition of GH, thyroid stimulating hormone, insulin and glucagon
4
Q
growth hormone-releasing hormone function (GHRH)
A
stimulation of GH
- also tropic for somatotrophs (helps them grow/survive)
- tropic = stimulates the release of another hormone
5
Q
what is the prolactin-inhibiting hormone
A
- dopamine
inhibits prolactin
6
Q
corticotropin-releasing hormone (CRH)
A
produced in response to stress. Stimulates secretion of products derived from proopiomelanocortin (POMC) like adrenocorticotropic hormone (ACTH)
7
Q
function of hypophysiotropic hormone
A
regulates the release of hormones from the ant pit; pulsatile
8
Q
what do somatotrophs secrete and where from
A
- growth hormone
- from ant pit
9
Q
what do lactotrophs secrete and where from
A
- prolactin
- from ant pit
10
Q
what do thyrotrophs secrete and where from
A
- thyroid-stimulating hormone (TSH)
- from ant pit
11
Q
what do corticotrophs secrete and where from
A
- ACTH
- from ant pit
12
Q
what do gonadotrophs secrete
A
- LH (luteinizing hormone) and FSH (follicular stimulating hormone)
- from ant pit
13
Q
what kind of receptor does gonadotropin-releasing hormone activate?
A
GPCR
14
Q
what are LH and FSH made of and what is their effects
A
glycoproteins
- LH: causes testes to produce testosterone
- FSH: causes ovaries to produce estrogen and testosterone
- stimulated by GnRH
15
Q
what acts synergistically with corticotropin-releasing hormone?
A
vassopressin and angiotensin act synergistically with CRH to mediate ACTH release
- VP = positive regulator of ACTH
16
Q
what inhibits corticotropin-releasing hormone
A
oxytocin
- negative regulator
17
Q
in addition to the ant pit, where is corticotropin-releasing hormone secreted?
A
placenta
as a preprohoromone? has a signal peptide AND a cryptic peptide
18
Q
what is a long lasting negative ACTH feedback
A
cortisol acts on hypothalamus or pit…
- can be fast or slow
19
Q
what is a slow long lasting ACTH neg feedback
A
nuclear
20
Q
what is a fast long lasting ACTH neg feedback
A
nonnuclear
21
Q
what inhibits prolactin?
A
dopamine (aka prolactin inhibiting hormone)
- this is the main regulatory hypothalamic hormone
22
Q
what does prolactin inhibit?
A
gonadotropin releasing hormone
- inhibits LH and FSH
- therefore inhibits ovulation in females and spermatogenesis in males (testosterone, estrogen, progesterone)
23
Q
what acts as a positive regulator for prolactin?
A
suckling on breasts
24
Q
what are thyrotrophs stimulated by?
A
thyrotropin-releasing hormone (TRH)
- hypothalamus
25
what are thyrotrophs inhibited by?
somatostatin
- hypothalamus
and by thyroid hormone, T3 and T4 (negative feedback loop)
26
what does the release of growth hormone stimulate
the production of IGF-1, the uptake of AA in tissues, lipolysis, protein synth in liver, opposes insulin's actions
27
what is the negative feedback for GHRH
- negative feedback on somatotrophs is autocrine
28
what is the release of GHRH from the hypothalamus inhibited by?
somatostatin
29
what hormone from the stomach has a positive effect on GH release?
ghrelin
30
what is the reciprocal hormone of GHRH
somatostatin
- decreases cAMP and therefore decreases synthesis of GH
(GHRH does the opposite)
31
what is found in the intermediate lobe
melanotrophs that produce the melanocyte-stimulating hormone (MSH)
32
what does ACTH do
- controls steroid secretion from the adrenal cortex (mineralcorticoids, cortisol, glucocorticoids)
33
what kind of receptor does ACTH bind to in the adrenal cortex?
melanocortin receptor
34
what does MSH stimulate in mammals
MSH stimulates melanocytes to produce melanin
| - deriver of tyrosine
35
what does MSH stimulate in frogs, octopus, fish
MSH stimulates the distribution of pigment in melanophores
36
what inhibits MSH production in the hypothalamus?
dopamine
37
if you do a test and there is low testosterone, LH and FSH where is the problem
gonadotrophin releasing hormone
38
if you do a test and there is normal LH and FSH but low testosterone what is the problem
problem with target gland in the testes??
39
vassopressin main function
osmoregulation (water balance) and pressure regulation (vassoconstriction), stress response (ACTH release)
40
oxytocin main function
uterine contraction and milk ejection
| also mother and offspring bonding
41
what does oxytocin inhibit
inhibits corticotropin-releasing hormone (CRH)/ vasopressin (VP) mediated ACTH release
- helps calm
42
what kind of receptor is the oxytocin receptor
GPCR
43
what does and increase in IP3 and therefore intracellular Ca2+ levels do (2)
1. myosin contraction in smooth muscle causing milk-release
| 2. NT release leading to bonding in humans and animals
44
causes of diabetes insipidus
1. hypothalamic
2. nephrogenic (mutation of VR receptor or aquaporin channels in collecting duct)
3. Gestational (when metabolism of VP increased during pregnancy)
45
what are the direct and indirect effects of GH
1. Direct: metabolism
| 2. Indirect: growth
46
Direct effect of GH
GH binds to GHR on fat cells, causes the breakdown of fats
47
Indirect effect of GH
GH causes liver to produce and secrete IGF-1. acts on bone/muscles etc and causes them to grow!
48
what acts as a negative feedback regulator for GH
increased IGF-1 concentration
49
what inhibits GH release
somatostatin
50
what enhances the release of GH
ghrelin from the stomach... binds to secretagogue receptor
51
what hormones are important for growth
TH
insulin
sex hormones
glucocorticoids - high concentration = reduced growth
52
what kind of receptor does GH bind to
cytokine receptor (tyrosine kinase separate)
53
what binds to a similar receptor as GH binds to?
interleukins (a cytokine)
54
what does JAK2 do in GH pathway?
tyrosine kinase
- phosphorylates itself, GHR, and STAT
- activate PI3K and MAPK pathways that lead to growth
55
what does ubiquitin do?
attaches to lysine in protein.
- turns cell signaling off
- signals for internalization and proteolysis in proteosome
56
what are 3 proteins that are important in growth hormone downregulation (and what do they do?)
1. ubiquitin
2. phosphatases
3. SOCS (suppressors of cytokine signalling)
- SOCS have SH2 domain that bind to JAK2 and STAT proteins and target for degradation
57
disease when there is too much GH after puberty
acromegaly
| - too much GH after puberty inc. in IGF1
58
causes of increased GH action
-enlarged pituitary from overstimulation of regulatory hormones (hypothalamic tumour)
- ectopic GH or GHRH
(acromegaly, gigantism)
59
causes of decreased GH action
```
GH resistance (reduced function of GHR, lowered GHBP)
- insensitivity to IGF-1
(laron's dwarfism, normal short kids)
```
60
what growth factors use cytokine receptors
erythropoietin (RBC), colony stimulating factors (WB), cytokines (immune cells), transforming growth factor beta (inc FSH, inhibits cell growth)
61
what kind of receptor does prolactin bind to?
cytokine receptor
62
growth factors that use growth factor receptors (tyrosine kinase receptors)
IGF-1, IGF-2, insulin, epidermal growth factor, nerve growth factor, platelet-derived growth factor
63
what is the MAPK pathway (and what does MAPK stand for)
- phosphorylation cascade... growth factor binding protein 2 (GRB2) binds, recruits RAS (rat sarcoma... small g-prot) and activates MAPK pathway
- mitogen-activated protein kinase
64
what does PI3K, and PDK stand for (phosphorylation cascade... what does it regulate)
- PI3K = phosphoinositide 3-kinase
- PDK = PIP3-dependent kinase
- growth factor signaling that effects glucose pathways
65
what kind of domains does GRB2 have
SH2 (recognizes phosphorylated tyr) and SH3 (recognizes proline rich)
66
what is a disease associated with too much growth FACTOR
CANCER
| - too little GF = failure to grow, apoptosis
67
what was the first oncovirus to be described
rous sarcoma virus
68
what does the rous sarcoma virus do
brings in v-src (src = encodes a tyr kinase) by mimicking c-src. This src lacks regulation because it is missing sites for phosphatase inactivation
- has tyr kinase ocogene, reverse transcriptase enzyme, and integrase enzyme
69
what are the effects of TH
regulates metabolism, cardiovascular and other hormone function
70
what is the most common endocrine disease. And what is the affected rate
thyroid hormone diseases (1/7 - more woman affected)
71
what affects the thyroid axis in NA
```
bisphenyl A (placticizers)
polybrominated biphenyl ethers (flame retardants)
```
72
what kind of sacs is the thyroid made of and what are these sacs filled with
made of sacs called follicles that are filled with colloid
73
how does TH get made and released
- thyrogobulin is produced, gets secreteed into colloid
- tyrosine residues on thyrogobulin are iodinated by thyroid peroxidase... this is TH attached to thyrogobulin
- when stimulated by TSH the thyrogobulin attached TH all get endocytosed
- Thyrogobulin degraded, free TH is released in blood!
74
what causes goitre?
not enough iodide
- TH not released no neg feedback therefore TSH keeps pumping
- enlarged thyroid gland
- causes goitre
75
what does too much iodine cause
downregulation of TH
76
what TH are active in the nucleus
T3, T4
| - only the T3 where the iodine gets removed from the outer ring
77
what inhibits and stimulates TSH release
inhibits: somatostatin (or T3, T4 neg feedback)
stimulates: thyroid releasing hormone (TRH)
78
what regulates TH
1) circadean rhythm and cold
2) glucocorticoid
3) chronic stress
4) excess iodide
5) autoimmune antibodies against TSH receptors
6) estrogen
79
**what does TSH stimulate
follicle growth and TH synthesis and secretion
80
what is T3 and T4 BBP?
thyroid-binding gobulin
81
what does low thyroid-binding gobulin result in?
hypothyroidism
82
how is TH trans into the cell and then into the nucleus?
- actively transported into the cell
| - diffuses into nucleus
83
3 different domains of nuclear receptor
1. amino terminus domain
2. DNA binding domain
3. ligand binding domain
84
function of the amino terminus domain
- ligand-independent transactivation
| other cofactors bind here
85
function of the DNA binding domain
- dimerization
86
function of the ligand binding domain
- hetero/homo dimerization
- ligand dependent transactivation
- ligand binding
- nuclear translocation
- association with heat shock proteins (ONLY STEROID RECEPTORS.. NOT THYROID RECEPTORS)
- TR STAY BOUND TO DNA IN NUC
87
what kind of dimer does thyroid receptor bind as
heterodimer
| - usually TR with retinoX?
88
what happens if it is a negative TRE and there is TRE + TR + TH?
REPRESSING
89
what are the genomic effects of TH
- apoptosis
| - proliferation
90
examples of TH apoptosis and proliferation**
apoptosis: increase in transcription of caspases
proliferation: increase in transcription of caspase 3 and cyclins, cyclin D moved to S-phase for DNA synthesis
91
what do TRb and TRa do?
TRb - autoregulates (represses w/o ligand and activates itself)
TRa - upregulated by TRb and 5' deiodinases to enhance activation
92
why was this a good paper to do
thyroid hormones are
1. highly conserved between species
2. measurable endpoint
3. affects metabolism, growth and development in vertebrates
93
when there was an increase in POP what happened to the TH receptors and the TH
TH receptor alpha increased when more POP
| TH (thyroxine) decreased with more POP
94
why were harbour seals a good model for this paper
1. abundant
2. non-migratory
3. biology and physiology well studied
4. has been used to determine POP hotspots and as a model for the relationship between contaminants and health effeects
95
what were the three sites used in the seal paper and what were they used for
1. Queen Charlotte Strait
- reference site (cleanest)
2. Smith Island
- medium conamination
3. Gertrude island
- most contamination
96
what site were TR's the highest
gertrude island (TRa and TRb significantly higher)
97
as PCB increases what happens to TT4 and TRa?
as PCB concentrations in water increases TT4 decreases and TRa increases
- R value shows how much these are correlated
- p-value shows the level of significance (here is 0.01)
98
characteristacs of POP's
- lipophilic
- bioaccumulate
- long half life
99
what thyroid hormones promote actin polymerization in rat brain cells
T4, rT3
100
what happens when baby has hypothyroidism
cretinism
101
what is graves disease characterized by (triad)
- goitre
- hyperthyroidism
- bulging eyes
102
3 symptoms of Hashimoto's disease
1. weight gain
2. lethargy
3. menstrual irregularity
4. depression
5. cold intolerance
103
symptoms of graves disease
1. weight loss
2. profuse sweating
3. cardiac arrhythmeas
4. bulging eye
104
why are deiodinases so important
- important for regulating metabolic processes
- regulating TH action during development
- and regulating feedback control of the thyroid axis
105
what causes graves disease?
autoimmune destruction of thyroid gland
106
what is on the ligand-independent transactivation domain of the nuclear receptor
Activation function 1 (AF-1)
- change confirmation without ligand
- can lead to coactivation or corepression
107
what is on the DNA binding domain
2 zinc fingers
- highly homologous
- allows dimerization and binding to hormone response element
108
what HRE binds as homodimers
invert and palendrome
| - estrogen R, glucocorticoid, mineralcorticoid, progesterone, androgen (response elements)
109
what binds as heterotimers
direct repeat
- TRE
- TR + retinoic X receptor (most common)
110
what is typical structure for ligand binding domain
12 a-helices and beta turn
111
what initiates mitochondria apoptosis and what does the mitochondria release
- initiated by p53, releases cytochrome c
| - caspase 9 then activated DNA is cut
112
what does the zona reticularis produce and what is it deficient in
produces cortisol and androgens
| - deficient in aldosterone enzymes (P450 aldosterone)
113
what does the zona fasiculata produce and what is it deficient in
produces cortisol and androgens
| - deficient in aldosterone enzymes (P450 aldosterone)
114
what does zona glomerulosa produce and what is it deficient in
produces aldosterone
| - deficient in cortisol and androgen enzymes (17-a hydroxylase)
115
what is the zona glomerulosa regulated by?
ACTH, and the renin-angiotensin system
116
what is abundant in the zona fasiculata
mitochondria, lipid droplet, SER
117
what does aldosterone promote (produced in ZG)
- Na+ retention K+ excretion
118
what does glucocorticoids promote (produced in ZF, ZR)
- protein and carbohydrate catabolism, gluconeogenesis,
119
what are sex steroids secreted from
zona reticularis (estrogen, androgens converted to testosteron)
120
what kind of receptors can glucocorticoids bind to?
glucocorticoid receptors OR mineralcorticoid receptors
121
how does cortisol travel in blood
- corticosteroid binding gobulin
| - albumin
122
what are cortisols functions
maintains normal glucose level in blood by:
- stimulating gluconeogenesis in liver
- inhibition of glucose uptake in muscle and adipose
- fat breakdown in adipose tissue
123
how do glucocorticoids reduce inflammation
- decrease enzymes involved in prostaglandins
| - induce apoptosis in lymphocytes (especially T cells)
124
how does glucocorticoids play a role in fetal developmetn
- involved in the development of many systems through the use of growth factors
- production of surfactant
- high levels of glucocorticoids inhibits growth in children
125
what enzyme converts cholesterol to pregnenolone
cytochrome p450 oxidase
126
how is cortisol synthesised (what receptor, what binds)
GPRC, ACTH binds
| - when PKA activated , cholesterol is released from lipid droplet
127
what are the proteins involved in changing cholesterol to pregnenolone
- stAR (steroidogenic acute regulatory protein) - puts cholesterol in mitochondria
- p450scc (modifies cholesterol side chains in mitochondria to change it to pregnenolone)
- SER can cange pregnenolone to cortisol
128
what hormone is a natural agonist, a synthetic agonist and a synthetic antagonist
agonist: cortisol
synthetic agonist: prednisone
synthetic antagonist: taximofen
129
hormones with BBP
- cortisol
- GH
- IGF-1
130
how iron levels are controlled
- anemia hypoxia in kidneys
- erythropoeiten is released (stimulates synth of RBC)
- as RBC increases, erythroferrone released from bone marrow
- erythroferrone stimulates the liver to produce hepcidin
- downregulates release of hepcidin (iron levels increase, from duodenum)
- this increases the carrying capacity of RBC
131
what does COPII do
mediates anterograde (COP = coat associated protein)
132
what does COPI do
mediates retrograde
133
what does clatherin do
mediates the transfer of vesicles from trans golgi to the membrane
134
what uses growth factor receptor (tyrosine kinase)
- insulin
- IGF-1
- epidermal growth factor
GF, GFR, SH2, SH3, MAPK3
135
what kind of signaling pathway is oxytocin a part of
GPCR
| gaq (muscle contraction for milk release)
136
what activates guanylyl cyclase receptor and what does it cause
atrial natriuretic peptide
| - causes high BP (vasodialation)
137
where is iron released from
gut liver WBC
