Endocrinology Flashcards
1
Q
What are the different types of cell communication?
A
Autocrine
Paracrine
Endocrine
2
Q
What determines the strength of autocrine signalling?
A
Depends on the amount of cells that are producing the signal and the amount of cells with the receptor for the signal
3
Q
What are the 2 types of hormones?
A
Lipid soluble
Water soluble
4
Q
How do lipid soluble hormones enter cells?
A
Transported in the blood by carrier proteins
Diffuse through plasma membrane
Expression of genes at the level of the nucleus
5
Q
How do lipid soluble hormones enter cells?
A
Dissolved in blood
Bind to receptors on the surface fo teh cells
= Intracellular events
6
Q
What are the different lipid soluble hormones?
A
Steroid hormones
Thyroid hormones
Retinoids
Vitamin D
7
Q
What are the different water soluble hormones?
A
Most signalling molecules like GF
Cytokines
EPO
8
Q
What hormones are produced in the adrenals?
A
Androgens
Cortisol
Corticosterone
Aldosterone
9
Q
What hormones are produced in the ovaries
A
Oestradiol
10
Q
What hormones are produced in the testes?
A
Testosterone
Dihydrotestosterone
11
Q
What is the action of a lipid soluble hormone on a receptor?
A
- Binding
- Receptor is activated
- Active receptor binds to DNA
- Regulates transcription of specific genes
12
Q
What do nuclear receptors work with?
A
nuclear receptors work with coactivator proteins which then regulate activation and repression of nearby genes
13
Q
What are the two ways that water soluble hormones can interact with membrane bound receptors?
A
Inhibitory
stimulatory
14
Q
What substances are involved in the intracellular signal transduction pathways?
A
Adenyl cyclase
Guanyle cyclase
Phospholipase C
Tyrosine kinase
Ion channels
15
Q
What can the binding of a water soluble ligand lead to in a cell?
A
Altered metabolism of a cell
Altered gene expression of a cell
Altered cell shape or movement
16
Q
Role of adenyl cyclase
A
ACTH, ADH, FSH, LH, TSH
17
Q
Role of Guanylyl cyclase
A
Rare atrial natriuretic peptide
18
Q
Role of phospholipas C
A
Hypothalamic hormones
TRH and GnRH
19
Q
Role of tyrosine kinase
A
Insulin
Prolactin
Growth hormone
IGF
20
Q
Role of ion channels with water soluble hormones?
A
hormones using multiple pathways
21
Q
What are the 3 components of the membrane receptor?
A
External domain
Transmembrane domain
Cytoplasmic/ intracellular domain
22
Q
What is the inter cellular signalling pathway for water soluble hormones?
A
Binds to extracellular hormone binding domain
Will affect the transmembrane domain and cause the cytoplasmic domain to undergo conformational change
23
Q
Growth factors
A
Polypeptides that promote cell growth or proliferation
24
Q
Cytokines
A
General term used for factors associated with blood cells (ie derived from immunology)
25
What processes are controlled by growth factors and cytokines?
Cell division and proliferation
Apoptosis
GF and cytokines are implicated in cancer
26
Why is the removal or termination of a signal important?
Signal reduction is required
Response fades once signal is withdrawn
Depends on rate of destruction of molecules that signals effects
Turnover rate depends on the promptness of the signal being turned on
Factors determine the half life of the signalling molecule
27
Define half life of a signalling moecule
Time taken for the concentration of a signalling molecule to fall by half
Determined by rate of synthesis and modifications of proteins
28
How can the same molecule have different effects?
ACh has different effects on the heart, salivary gland and the skeletal muscle
All dependent on the receptor it binds to
29
What are the main cell surface receptors?
Ion channel liked receptors
G protein linked receptors
Tyrosine kinase linked receptros
Receptors with intrinsic enzymatic activity
30
Examples of ion channel linked receptors
Postsynaptic membranes
Neuromuscular junction
Nicotinic acetylcholine receptor
GABA receptors
31
What are the second messenger molecules and how do they work?
Small intracellular signalling molecules
generated in large numbers by activation of receptor= amplification of signal
Diffuse away rapidly
Pass on signel by binding to and altering the behaviour of other proteins
Exhibit different ways of passing the signal on
32
Give some examples of second messenger molecules
cAMP
cGMP
Ca2+
Diacylglycerol
33
What are the functions of intracellular proteins?
Scaffolds
Relays
Adaptors
Amplifiers
Modulators
34
What are the key processes in cell signalling?
Protein phosphorylation - protein kinase and phosphoprotein phosphatase
Reversal of protein phosphorylation
35
What are the types of protein phosphorylation?
Phosphorylation of serine/threonine residues
Phosphorylation of tyrosinwe residues
phosphate is added by signal transduction
36
What is 7 transmembrane?
Single polypeptide chain with central hydrophobic region that spans the plasma membrane 7 times
receptor protein interaction = mediated by 3rd protein (G protein)
target is enzyme or ion channel
37
G protein
Guanine nucleotide binding protein
Signal transduction protein
38
What are the 3 main steps of the G protein mediated signal transduction?
No ligand = inactive receptor
Binding of ligand recruits G protein complex
GTP replaces GDP when g alpha and bet proteins dissociate and their subunits regulate second messengers
39
What are GaS and GaI G proteins?
Stimulatory
Inhibitory
40
How do stimulatory effects mediate the adenylate cyclase system?
1. Subunit of G protein activated to adenylate cyclase
2. ATP converted to cAMP
3. cAMP is a catalytic subunit of protein kinase A
3. pkA is part of the cascade of intracellular phosphorlations
41
What are the 2 types of enzyme linked receptors?
Function directly as enzymes (intrinsic enz activity)
Directly associated with enzymes they activate (associated enz activity)
42
What is the signal transduction pathway for tyrosine kinase receptors?
Ras signal transduction pathway
Phosphoinisitide 3 kinase pathway (PI-3 kinase)
Phospholipase C
43
What is the Ras pathway?
Ligand and receptor bind -> ras pathway is protein kinases are used and formed _> protein kinases pass through nuclear pore= transcription factors activated
Gene activation occurs
Cellular response
44
What are the 6 classes of enzyme linked receptors?
- receptor tyrosine kinases- Phosphorlyate tyrosines on intracellular signalling molecules
- Tyrosine kinase-associated receptors- Associate with intracellular proteins with tyrosine kinase activity
- Receptor-like tyrosine phosphatases- Remove phosphate groups from tyrosine on intracellular proteins
- receptor serine/threonine kinases- Phosphorylate serines or threonines on regulatory proteins
- Receptor guanyl cyclases- Catalyse production of cytosolic cGMP
- Histidine-kinase-associated receptors
45
How do histidine kinase associated receptors work?
Two component system - kinase phosphorylated itself
Passes on phosphate to intracellular signalling protein
46
What are the 2 intracellular molecular switches?
Made of intracellular protein and signal - switch from active to inactive
Signalling must recover
Switch operates by gain or loss of phosphate groups
47
What are the 2 main classes of molecular switch?
Phosphorylation (removal of Pi inactive- kinase adds Pi active)
GTP binding (GDP inactive- GTP active)
48
In general steroid hormones have a ______ effect on cells
Slower by stronger effect
49
In general water soluble hormones have a _________ effect on cells
Faster but less intense effect on cells
50
What are the 4 organ endrocrine glands?
Heart = ANP
Intestine= cholecystokinin
Kidney= 1, 24 dihydroxycholecalciferal and EPO
Placenta= chorionic gonadotropins
51
What are the function classifications of hormones?
Classical hormones
Neurohormones
Local hormones
52
What are classical hormones?
Endocrine cells -> blood -> target tissue
Like cortisol a steroid hormone secreted by the adrenal cortex
53
What are neurohormones?
Neuroendocrine cells-> nerve terminals-> blood
Like cortico releasing hormone - produced by hypothalamus= ACTH from the ant pit-> adrenal = cortisol
54
What are local hormones?
Paracrine and autocrine hormones that diffuse into the interstitial fluid
55
Epinephrine
Catecholamine - freely transported
56
How are lipid soluble hormones transported?
Bound to transport proteins
Cortisol binding globulin
57
What are the main specific lipid soluble binding hormones?
Cortisol binding protein -> cortisol
Vitamin D binding globulin = Vit D
Thyroid binding globin = T 3 and T4
58
What are the non specific lipid soluble binding hormones?
Albumin -> steroids
Prealbumin -> T3 and T4
59
Where can thyroid hormones be found in the blood?
0.3% fT3
0.03% fT4
70-80% bound to thyroid binding globulin
Rest is bound to albumin and free albumin
Bound hormones have a high concentration
Free hormones have a low concentration
60
What affects total hormone concentrations?
Binding protein conc
Hormone level
61
How do transport proteins function?
Serves as a hormone reservoir- free diffuse into cell, replace free hormones in the blood
Act as hormone buffer - resp to inc horm conc - short term peaks absorbed, dont necessarily stim tisues
reduce hormone loss from the kidneys- Larger so dont enter ultrafiltrate
62
What are plasma concentrations the net result of?
Rate of secretion into bloos
Rate of removal from the blood
63
What are the different elimination mechanisms?
Enzymatic degradation
within target cells after binding
Via liver and kidneys
64
How is elimination and function of epinephrine related?
Epi= fight or flight hormone
rapid release from adrenal medulla = immediate action on heart and tissues
Fast return to normal
Water soluble hormone binds to receptors and is enzymatically degraded
65
How is elimination and function of T4 (thyroxine) related?
Slow action hormones
T4 is predominantly bound
Bound is resistant to degradation
FreeT4 -> T3 to enter cell and alter gene expression or converted to water sol by liver and excreted in urine
66
What factors affect hormone response?
Variation by tissue
variation by time
variation by dose
status of target tissue
67
How can the variation of tissue affect the action of thyroxine?
T4 increases cellular metabolism measured as O2 consumption
48 hrs after injection most stimulated tissues are heart and gastric mucosa
Least stimulated = skeletal musc
Not stim= brain and spleen
68
How does time affect variation of hormone action?
Initial response of hormone may differ from delayed responses
69
How is there variation by dose and duration of hormones?
Response associated with hormone is for physiological range
Hormones outside normal range = diff response
Dex steroid short course = no adverse affects
Long course= clinical signs of cortisol excess
70
How will targets tissue status affect hormone function?
overstimulation = hypertrophy = more functional= exaggerated response
Under stimulation = atrophy = less functional
71
How does dexamethasone withdrawal cause issues?
Immunosuppressive doses for auto immune disease
Dexamethasone suppresses normal syth and secretion of steroid from adrenal gland
Adrenal gland atrophy
Sudden withdrawal = crisis
72
What units are used for measuring hormones?
picomol
Nanomol
73
What diagnostic kits can be used to measure hormones?
Radioimmunoassay
ELISA
74
Clearance rate
Use of radioactively labelled hormone or halt secretion
75
Secretion rate
If concentration rate remains stable then it is assumed secretion = clearance
76
How do feedback loops play a role in hormone secretion?
Negative feedback
hormone exceeding necessary levels
High level is sensed by hypo or pit gland
= decrease in hormone synth
free hormone levels monitored and adapts to changes in the binding protein
77
Main water soluble hormones
Glycoproteins
Catecholamines
Peptide hormones
Calcitonin
Epinephrine
Thymosin
Melatonin
78
Which hormones exclusively uses adenyl cyclase pathway?
Insulin
ADH
glucagon
79
What is the adenyly cyclase pathway?
Pathway regulated by GaS and GaI
Any reaction where ATP is converted to cAMP uses this pathway
80
Which hormone exclusively uses the phospholipase C pathway?
PTH
TSH
81
Which hormones exclusively uses the tyrosine kinase pathway?
peptide hormones like insulin, and growth hormones
such as IGF-1
Growth hormone
82
ANP
Atrial natiuretic peptide - increases renal excretion of salt and water, vasodilation, inc vasc permeability
uses guanylate cyclase transduction system (cGMP)
83
What can somatotropes become?
GH
Somatotropin
Somatotrophic hormoen
84
How is growth hormone regulated?
GH in liver produces IGF-1 or somatomedin C
these stim GHRIH or somatostatin in order to inhibit release of GHRH from hypothalamus
IGF 1 directly inhibits GH release from Ant pit
Grehlin stims GH release from pit
Negative feedback loop
85
What is the long term and short term actions of GH?
Long = promoted growth- protein synthesis
Short= starvation response = lipolysis and insulin resistance
86
What receptors does growth hormone require?
STAT1 and STAT2 receptor mechanisms
Needs a surface receptor and a second messenger hormone
87
What growth response is produced by GH?
inc nuclear transcription
inc translation
inc aa transport through cell membrane
dec catabolism of proteins and aa
88
What are the different stimuli for the starvation response by growth hormone?
dec blood glucose
dec free FA
dec protein
Trauma stress excitement
Exercise
89
What are the properties and actions of IGF1?
lnsulin mimicer
Stim by GH
produced mainly in liver
Inc chondrogenesis and growth
Inc chondrocytes and osteogenic cell replication and protein for more bone growth
Chondrocytes-> osteoblasts = new bone
90
Affect of IGF1 on bone growth?
Open growth plates or epiphyseal cartilage
GH inc cartilage deposition
GH stim osteoblasts
Cartilage minerlises inc bone length
Closed growth places
Epiphyseal cartilage fused to bone shaft
91
Pituitary dwarfism
autosomal recessive condition causes proportionate growth retardation, soft wooly hair
2-3 months of age
mutation in LHX3 that regulates pit stem cell differentiation
Defect after corticotrope differentiation so ACTH not affected
Decreases GH,TSH prolactin and gonadotropins
+/- pitui cyst
92
How does pituitary dwarfism affect the repro tract?
Males = unilateral or bilateral crytochidism
Females= persistent oestrus , failure to ovulate
93
How is a diagnosis of pituitary dwarfism made?
decreased GH - species specific radio immunoassay
dec IGF-1 - longer half life, less species spec aa sequence - human assay
94
What occurs with GH excess?
Giantism= develops in young patients before closure of epiphyses
Acromegaly= develops in adult patients after closure of epiphyses, inc soft tissues over eyes, macroglossia, inc interdental space, organomegaly
95
Feline acromegaly
Middle age- old = 90% female
Pituitary tumour secreting excess GH
Diabetic at presentation (caused by insulin resistance)
96
Canine acromegaly
Middle- old
ALWAYS female
excess exogenous progesterons and endogenous progesterone
Induction of GH gene in mammary glands
mammary GH = normal GH
97
Acromegaly diagnosis?
IGF-1 conc
GH conc - species spec assay
supportive clinical signs and lab work w normal thyroid adrenal testing
98
Chromophobes stain ________ while chromophils stain _________
chromophobes stain poorly while chromophils stain well
99
What are the two types of chromophils?
Acidophils - acid dyes somatotropes and lactotropes, mammotropes, luteotropes
Basophils - Basic dies
Cortictropes, thyrotropes, gonadotropes
100
What are the most and least dense cells of the pars distalis?
Most = somatotropes = GH 50%
Least = thyrotropes = TSH 5%
All the others make up 15-20%
101
what is grehlin
a hormone from the stomach that releases growth hormones in response to food
102
Which 3 hormones regulate growth hormone secretion
Grehlin
GHSH
Somatostatin
103
What is the role of the growth hormone?
- Stimulates IGF-1 secretion from the liver
- Growth
- Stimulates protein synthesis (anabolic effects)
- Stimulates lipolysis (mobilizes fatty acids and glycerol)
- Inhibits glucose utilisation (inhibits insulin)
104
What are the 2 forms of lactotropes and when is each relevant?
Lactotropes may be chromophils when storing PRL in the cytoplasm
However, lactotropes are chromophobes when PRL has been released
105
How are lactotropes regulated?
-
1. Tonic inhibition by dopamine via the D2 receptors
2. Lactotropes can be stimulated by TRH
3. There is hypertrophy of lactotropes during pregnancy for lactation
106
What is produced by the corticotropes?
POMC (proopiomelanocortin)
Proteolytic hormones cleave POMC into
- Adrenocoticotropine hormone
- Melanocyte-stimulating hormone
- beta-lipotrophic hormone
- beta-endorphin
- enkephalin
- corticotropin-like intermediate lobe peptide (CLIP)
107
What is enkephalin?
A type of endorphin
108
What controls the local production of POMC derived hormones?
Discrete localisation of processing enzymes within the anterior pituitary
Prohormone convertase I
Prohormone convertase II
109
How are corticotropes regulated>
-
1. By corticotropin-releasing hormone
2. Tonic stimulation
3. By a negative feedback loop
More corticotropin-releasing hormone increases the ACTH secretion
Less corticotropin-releasing hormone decreases ACTH secretion
110
How are gonadotropes regulated?
1. By GnRH from the hypothalamus
2. In a negative feedback loop
111
Describe the structure of the pars intermedia?
- The pars intermedia is a series of small cystic cavities
- It has follicles filled with colloid
- The pars intermedia originated from the residual lumen of Rathke’s pouch
- Contains Basophils and chromophobes
- The pars intermedia extends into the pars nervosa
112
What is the role of the pars intermedia in horses>
Referred to as melanotropes in horses
Where prohormone POMC is converted into MSH
Not under negative feedback control
113
Closed feedback loops
Target cells secreted hormones that affect their own secretion
There is feedback regulation that is usually negative
114
Describe open feedback loops
There is no direct feedback
Instead, they are stopped by the removal of the stimulus or depletion of biochemicals
Stimulation of milk let down
115
What are the 4 independent systems?
1. Glucose regulation
2. Calcium regulation
3. Sodium and potassium regulation
4. Gastrointestinal enzyme secretion
116
How do hormone deficiencies occur?
1. There is less functional tissue to produce to hormone
2. Interference with hormone synthesis
3. Less stimulation from higher in the pathway
117
How can loss of negative feedback occur?
Hormone from tissue that was never under negative feedback control
Tissue continues secreting hormones regardless of stimulating hormone
118
What are the pituitary neoplasms
Adenomas of the pars distalis or intermedia
GH secreting pars distalis tumour
119
What is the affect of a GH secreting pars distalis tumour?
- Affects the acidophils within the pars distalis
- very rare
- There is an excess of growth hormone (and IGF-1 from the liver)
- This alters the growth and affects energy metabolism
- Differential diagnosis for diabetes mellitus
120
Where is the thirst centre located>
Hypothalamus
Input from osmo and stretch receptors
Info -> ADH producing neurones to PP -> capillary bed
121
How does ADH increase AQP density on the tubule surface?
Aquaporin-2 is under ADH control
1. ADH binds to receptors
2. Activation of adenyl cyclase occurs
3. This produced cAMP
4. Vesicles containing aquaporins move to the cell surface
5. Inserted via exocytosis
6. Proportional to plasma ADH concentration
7. They are then removed by endocytosis
122
What is DI>
Diabetes increased urine output
Insipidus is caused by ADH dysregulation
123
What are the 2 types of DI?
Neurogenic= inadequate ADH from pit
Nephrogenic = inadequate nephron response
124
How is DI diagnosed>
Injection of exogenous ADH
if the urine is concentrated then it is neurogenic DI
If the urine is dilute then it is nephrogenic DI
125
What causes congenital diabetes insipidus?
AQP-2 deficiency
Nephrogenic
126
What is the neuronal transmission from the mammary glands?
-sensory nerve fibres in the teats detct the suckling
- Impulses transmitter via the superficial sensory pathways and inguinal nerve
- Afferent sensory neurones enter the lumbar segments of the spinal cord
- Ascend the spinal cord sensory tracts
- To the thalamus, influence cell bodies of neuroendocrine cells
- Secretion of oxytocin from nerve endings in PP
127
What is the role of oxytocin once released in the mammary gland>
1. Increases pressure within the alveoli
2. Reduced resistance in excretory ducts
3. Reduced resistance in the teat canal
4. The result is increased milk outflow
128
Describe the physiology of oxytocin in the mammary gland
-
1. Binds to receptors on myoepithelial cells
2. Myoepithelial cells surround alveoli and walls of small secretory ducts
3. Oriented along the long axis of the secretory duct
4. The duct becomes shorter and wider
5. Opposite effect on circular sphincter muscle of teat - causes relaxation
6. Both actions increase the milk flow
129
What are the stages of parturition?
- Stage 1
Myometrial contractions and dilation of the cervix
- Stage 2
Expulsion of the fetus through the birth canal
- Stage 3
Expulsion of placenta
130
What is the neuroendocrine reflex during birth?
- Stimulate sensory nerve endings in the cervix
- Afferetn nerve impulses to the hypothalamus
- Neuroendocrine cells of the paraventricular and supraoptic nuclei depolarize
- Secrete oxytocin from pars nervosa
- Enters blood circulation
- Act on oxytocin receptors of myometrium
- Strong uterine contractions
131
Outline the biological clock mechanism
1. Light is sensed by the retina
2. transmitted via nerve pathways
3. Arrive at hypothalamus
1. Specifically the suprachiasmatic nucleus
4. Stimulates the pineal gland and other pathways
132
Define sensitivity
The true positive rate
Measures the proportion of actual positives which are correctly identified as such
the percentage of healthy horses who are correctly identified having PPID
133
Define specificity
The true negative rate
Measures the proportion of actual negatives which are correctly identified as such
- The % of healthy horses who are correctly identified as not having PPID
134
How can we differentiate between PPID and EMS?
signalment and other clinical signs
ACTH does not increase with EMS
Difficult when animal is stressed
