endocrine basic principles Flashcards
1
Q
what makes up the diencephalon
A
thalamus and hypothalamus
2
Q
what makes up the rhombencephalon (hindbrain)
A
medulla oblongata
pons
cerebellum
3
Q
how is the action of a hormone terminated
A
enzymes
4
Q
what are the 3 categories of hormones
A
modified amino acids (amines)
steroid hormones
protein and peptide hormones
5
Q
adrenaline is an example of what kind of hormone
A
amine
6
Q
cortisol is an example of what kind of hormone
A
steroid
7
Q
progesterone is an example of what kind of hormone
A
steroid
8
Q
melatonin is an example of what kind of hormone
A
amine
9
Q
insulin is an example of what kind of hormone
A
protein/peptide
10
Q
ACTH is an example of what kind of hormone
A
protein/peptide
11
Q
testosterone is an example of what kind of hormone
A
steroid
12
Q
ADH is an example of what kind of hormone
A
protein/peptide
13
Q
oxytocin is an example of what kind of hormone
A
protein/peptide
14
Q
thyroid hormones are an example of what kind of hormone
A
amine
15
Q
GH is an example of what kind of hormone
A
protein/peptide
16
Q
prolactin is an example of what kind of hormone
A
protein/peptide
17
Q
what are amine hormones derived from
A
tyrosine and tyramine
18
Q
how/when are amine hormones synthesised
A
pre-synthesised within cells
19
Q
how are amine hormones stored?
A
in vesicles
20
Q
what causes amine hormones to be released
A
Ca2+-dependent exocytosis
21
Q
how are amine hormones transported
A
free in plasma as they are hydrophilic
except thyroid hormones - they are free and bound
22
Q
where are the receptors for amine synthesis
A
on cell membrane
23
Q
what is the half life of amine hormones
A
seconds
24
Q
what are steroid hormones derived from
A
cholesterol
25
when are steroid hormones synthesised
synthesised and secreted on demand
26
how are steroid hormones synthesised
stimuli increases cellular uptake and availability of cholesterol and rate of conversion of cholesterol to pregnenolone
27
what is the rate limiting step in the synthesis of steroid hormones
rate of conversion of cholesterol to pregnenolone
28
how are steroid hormones transported
in plasma mainly bound to plasma proteins
29
are steroid hormones active when bound or free
free
30
where are the receptors for activating steroid synthesis
within cells
31
what is the half life of steroid hormones
hours/days
32
why is the half life of steroid hormones long?
due to extensive binding to proteins that suppress elimination
33
what are protein/peptide hormones made from
proteins
34
how are protein/peptide hormones made
pre-synthesised usually from a longer precursor - proteolytic steps by convertases during intracellular transport
35
how are protein/peptide hormones stored
in vesicles
36
how are protein/peptide hormones released
in response to stimuli by Ca2+ dependent exocytosis
37
are protein/peptide hormones hydrophobic or hydrophilic
hydrophilic
38
how are protein/peptide hormones transported in the blood
free
39
where are the receptors for peptide synthesis found
on cell membrane
40
what is the half life of peptide hormones
minutes
41
in what state can hormones cross the capillary wall to activate receptors in target tissues (biophase)
free
42
give 3 functions of carrier proteins
increase amount of hormone transported in blood
provide a reservoir/buffer of hormone
extend half life of hormone in circulation
43
what does albumin bind
many steroids and thyroxine
44
what does transthyretin bind
some steroids and thyroxine
45
what does cortisol binding globulin bind
cortisol (and aldosterone) selectively
46
what does thyroxine binding globulin bind
T4 (and some T3) selectively
47
what does sex steroid binding globulin bind
mainly testosterone and oestradiol
48
what happens if free hormones diffuses out of the blood into cells
bound and free hormones in blood are in equilibrium - bound hormone will be freed to replace it
49
what happens if lots of hormone is suddenly secreted
free carrier proteins are available to bind them
50
what is the primary determinant of plasma concentration of a hormone
rate of secretion
51
what is the equation of plasma concentration of a hormone
plasma concentration of hormone = rate of secretion - rate of elimination
52
what are the 2 broad types of hormone receptors
| are the ligands hydrophilic or lipophilic for each?
cell surface receptors - ligand is hydrophilic
| intracellular receptors - ligand is lipophilic
53
what are the 2 types of cell surface receptors
GPCRs
| receptor kinases
54
what hormones activate GPCRs
amines and some peptide/proteins
55
what hormones activate receptor kinases
some proteins/peptides
56
what are the 3 types of nuclear receptor (intracellular receptors)
```
class 1
class 2
hybrid class
```
57
what hormones activate class 1 nuclear receptors
many steroid hormones
58
where are class 1 nuclear receptors located in the absence of an activating ligand and what are they bound to
mainly located in the cytoplasm
| bound to inhibitory heat shock proteins
59
where to class 1 nuclear receptors move when they are activated
to nucleus
60
what hormones activate class 2 nuclear receptors
lipids
61
where are class 2 nuclear receptors located
nucleus
62
what hormones activate the hybrid class
T3 (and others) - similar function to class 1
63
how does insulin signal
receptor kinases
64
where does insulin bind to receptor kinases
alpha subunit
65
what does binding of insulin to the alpha subunit of receptor kinases cause
beta subunits to dimerise and phosphorylate themselves (autophosphorylation)
(autophosphorylation of intracellular tyrosine residues)
66
what does autophosphorylation of intracellular tyrosine residues cause
recruitment of multiple adapter proteins e.g. IRS1 (insulin receptor substrate 1) that are also tyrosine phosphorylated ---> protein kinase B --> metabolic effects/catalytic activity of the receptor
67
what channels cause glucose entry into cells upon insulin binding
GLUT4
68
true/false
| GLUT4 channels remain in the cell membrane at all times
false - stimulated to move to cell membrane when insulin binds
69
how do steroid hormones enter cells
diffusion across plasma membrane
70
what does binding of a steroid hormone to an intracellular nuclear receptor cause
dissociation of inhibitory heat shock proteins (HSP)
71
in the case of steroid hormones, where is the inactive receptor located
in the cytoplasm
72
where does the receptor-steroid complex move and what does it do there
moves to the nucleus
forms a dimer
binds to hormone response elements in DNA
73
what does binding to the hormone response elements cause
transactivation or transrepression
| - alter mRNA levels and rate of synthesis of mediator proteins
74
what is transactivation
transcription of specific genes is switched on
75
what is transrepression
transcription of specific genes is switched off
76
how do glucocorticoids cause transactivation
binding of the activated glucocorticoid receptor homodimer to a GRE in a promoter region of steroid sensitive genes
77
what does binding of the activated glucocorticoid receptor homodimer to a GRE in a promotor region of steroid sensitive genes cause
transcription of genes encoding anti-inflammatory mediators
78
what does the glucocorticoid-receptor-corticosteroid complex interact with to cause transrepression
large co-activator moleules with intrinsic HAT (histone acetyltransferase) activity which is activated by proinflammatory transcription factors
thus, switching off inflammatory gene expression that are activated by these transcription factors
79
where is ADH released from
posterior pituitary
80
what does ADH cause and how
water reabsorption from renal tubules by counter current multiplication
81
what steroid controls sodium balance
```
aldosterone mainly
(also others e.g. cortisol)
```
82
what does aldosterone do to Na conc
Na reabsorption in renal tubules in exchange for K+/H+
83
```
increased pulse
dry mucous membranes
soft/sunken eyeballs
decreased skin turgor
decreased consciousness
decreased urine output
postural decrease in BP
- all indicate what?
```
decreased {Na+} / decreased ECF
84
what can cause decreased Na
increased Na loss
decreased Na intake
decreased water excretion e.g. SIADH
increased water intake
85
```
coughing
tiredness
SOB
pulmonary oedema
weak heart
peripheral oedema
ascites
pleural effusion
- all indicate what?
```
increased [Na+] - increased ECF
86
what can cause increased Na
increased Na intake e.g. IV meds, near drowning, malicious
decreased Na loss
increased water loss e.g. diabetes insipidus
decreased water intake
87
what qualifies as life threatening levels of sodium
< 120 nmol
> 160 nmol
if Na rises or falls rapidly even if to a point in normal range
88
where would 5% dextrose go
plasma
interstitial fluid
intracellular fluid
89
where would 0.9% saline go
plasma
| interstitial fluid
90
where would plasma/blood go
plasma
91
what are some s/s of life threatening hypo/hypernatraemia
altered consciousness
confusion
nausea/vomiting
fitting
92
what does [Na] reflect
Na loss
93
what does [K] reflect
K retention
94
what are some physiological causes of raised prolactin
breast feeding
pregnancy
stress
sleep
95
what are 5 drugs that cause raised prolactin
```
dopamine antagonists e.g. metoclopramide
antipsychotics e.g. phenthiazines
antidepressants e.g. TLA, SSRIs
oestrogens
cocaine
```
96
would hypothyroidism cause raised or lowered prolactin
raised
97
would a prolactinoma cause raised or lowered prolactin
raised
98
would a stalk lesion (iatrogenic, RTA) cause raised or lowered prolactin
raised
99
what does aldosterone do to the blood pressure
raised BP
100
does aldosterone increase parasympathetic or sympathetic outflow
sympathetic
101
what effect does aldosterone have on the heart/BVs
increased cardiac collagen
LVH
atheroma
altered endothelial function/increased pressure response
102
what GPCR do adrenaline, glucagon and CRH signal via
Gs
103
what does Gs do to the production of cAMP from ATP by adenylyl cyclase
increases it
104
what does increased cAMP do
stimulates protein kinase A leading to phosphorylation of Ser/Thr residues in target proteins
105
what GPCR does melatonin signal via
Gi
106
what does Gi do to the production of cAMP from ATP by adenylyl cyclase
decreases it
107
what GPCR do angiotensin II, GnRH and TRH signal via
Gq
108
what does Gq do to the activity of PLC (phosolipase C)
increases it
109
what is the role of PLC in the Gs pathway
converts PIP2 to DAG and IP3
110
what does IP3 do
binds to IP3 receptor on the endoplasmic reticulum causing calcium release to cause cellular effects
111
what does DAG do
stimulates protein kinase C causing phosphorylation of Ser/Thr residues in target proteins leading to cellular effects
112
what does the kidney release when BP falls
Renin
113
what does renin do
converts angiotensinogen to angiotensin I
114
how does angiotensin I get to angiotensin II
ACE
115
what does angiotensin II do
causes BP to rise
| stimulates adrenal gland to produce aldosterone
116
what does aldosterone do to increase the BP
salt retention
117
what is released from the hypothalamus to stimulate the anterior pituitary to produce ACTH
CRH
118
what causes the hypothalamus to release CRH
time of day
stress
illness
119
where does ACTH act and what does it cause
stimulates adrenal cortex to produce cortisol
120
what effect does increased cortisol have on CRH and ACTH levels
negative feedback - cortisol goes up, CRH and ACTH go down
121
how is adrenaline and noradrenaline released from the adrenal gland
direct control by nervous system
122
where is MSH released and where does it act
anterior pituitary
| melanocytes
123
where are LH and FSH released from and where do they act
anterior pituitary
| ovaries and testes
124
where is ADH released from
posterior pituitary
125
where is oxytocin released from
posterior pituitary
126
where does oxytocin act
uterine smooth muscle and mammary glands
| smooth muscle in vas deferens and prostate gland
127
where is PRL released from
anterior pituitary
128
where does PRL act
mammary glands
129
where is GH released from
anterior pituitary
130
where does GH act
liver
| also adipose tissue and target tissues
131
what does GH cause the liver to produce
somatomedins
132
where do somatomedins work
bone, muscle etc
133
where is TSH released from
anterior pituitary
134
what does TSH cause the thyroid to produce
T3 and T4
135
what does ACTH cause the adrenal gland to produce
glucocorticoids
136
what gland is under direct control by the nervous system
adrenal gland
137
what gland is under indirect control through release of regulatory hormones
anterior pituitary
138
where are oxytocin produced and stored
produced in hypothalamus
| stored in posterior pituitary
139
where is ADH produced and stored
produced in the hypothalamus
| stored in posterior pituitary
140
what hormone from the hypothalamus causes ACTH to be released
CRH
141
what hormone from the hypothalamus causes TSH to be released
TRH
142
what hormone from the hypothalamus causes LH/FSH to be released
GnRH
143
what hormone from the hypothalamus causes GH to be released
GHRH
144
what hormone from the hypothalamus inhibits prolactin
dopamine (DA)
145
what hormone from the hypothalamus inhibits GH secretion
somatostatin (SS)
146
what does GH cause the liver to produce
IGF-1
147
where does IGF-1 act
target tissues
148
what does GH cause adipose tissue to produce
leptin and free fatty acids
149
what effect do free fatty acids have on hypothalamus
negative feedback
150
what effect does leptin have on the hypothalamus
positive feedback
151
what kinds of things stimulate the hypothalamus to produce GHRH
```
ghrelin
sleep
exercise
stress
amino acids
sex hormones
```
152
what effect does IGF1 have on the anterior pituitary and hypothalamus
negative feedback
153
what effect does GH have on the hypothalamus
negative feedback
154
what feedback does PRL have on the hypothalamus
positive feedback
155
what feedback does PRL have on the anterior pituitary
negative feedback
156
what kind of signalling does PRL show at the breast tissue
paracrine/autocrine
157
what stimulates the hypothalamus to cause ADH release from the posterior pituitary
fall in BP
158
what does V1 do
constricts blood vessels to increase systemic vascular resistance and increase blood pressure
159
what does V2 do
causes fluid reabsorption in the kidneys to increase blood volume and increase blood pressure
160
how is glucose taken up into pancreatic beta cells
GLUT2 transporter
161
what happens after the uptake of glucose into pancreatic beta cells
glucose is phosphorylated by glucokinase
162
how are the Katp channels inhibited in the pancreatic Beta cells and how does this eventually lead to insulin release
phosphorylation of glucose by glucokinase increases intracellular ATP which inhibits Katp channels. This causes depolarisation of the cell membrane which leads to opening of voltage gated Ca2+ channels
increase in Ca2+ conc. leads to fusion of secretory vesicles with the cell membrane and release of insulin
163
what is released by pancreatic alpha cells
glucagon
164
what is released by pancreatic delta cells
somatostatin
165
what is released by pancreatic PP cells
pancreatic polypeptide
166
how and where is insulin synthesised
in the RER of pancreatic beta cells as a larger single chain preprohormone - preproinsulin which is cleaved to form insulin
167
what is the structure of insulin
2 polypeptide chains linked by disulfide bones
168
what is a biproduct of insulin formation
C-protein
169
how is the release of insulin described
biphasic
170
what % of insulin is from a readily releasable pool
5%
171
what happens to the curve of insulin secretion in poorly controlled type 2 diabetes
curve flattens and weakens
172
at what blood glucose should B cells produce insulin
over 5mM
173
what happens in type 1 diabetes
destruction of beta cells
174
what is glucokinases Km for glucose
within the physiological range of concentration - change in glucose conc leads to a dramatic change in glucokinase activity
175
how do beta cells lose ability to sense changes in glucose in other types of diabetes
hyperglycaemia takes glucose conc. outwith the Km of glucokinase, mitochondrial exhaustion
176
the Katp channel is a ____ complex and consists of 2 proteins - pore subunit and regulatory subunit
octomeric complex
| consists of 2 proteins
177
what makes up the pore subunit
4 potassium inward rectifier 6.2 subunits
| Kir6.2
178
what makes up the regulatory subunit
4 sulphonylurea receptor 1 subunits
| SUR1
179
what does the tetramer of Kir6.2 subunits form
K selective ion channel
180
what happens to the Katp channel when extracellular glucose is high
ATP binding to each of the Kir6.2 subunits closes the channel causing depolarisation of the beta cell and insulin release
181
what happens to the Katp channel when extracellular glucose is low
ADP-Mg2+ binding to the SUR1 subunits opens the channel maintaining the resting potential of the beta cell and inhibiting the secretion of insulin
182
what does diazoxide do to the Katp channel
stimulates the Katp channel inhibiting insulin release
183
what can some mutations in Kir6.2 lead to and how
neonatal diabetes
| constitutively activated Katp channels or increase in Katp numbers
184
what may some cases of neonatal diabetes respond to
sulfonylureas e.g. tolbutamide
185
what else could a Kir6.2 mutation lead to
congenital hyperinsulinism
| trafficking or inhibiting mutations
186
what could be used to treat congenital hyperinsulinism
diazoxide
187
what does insulin do to amino acid uptake in muscle
increases
188
what does insulin do to DNA synthesis
increases
189
what does insulin do to protein synthesis
increases
190
what does insulin do to lipolysis
inhibits
191
what does insulin do to gluconeogenesis in liver
inhibits
192
what does insulin do to glycogen synthesis in liver and muscle
increases
193
what does insulin do to glucose uptake in muscle and adipose tissue
increases
194
what does insulin do to lipogenesis in adipose tissue and liver
increases
195
what is another name for donotive syndrome
leprechaunism
196
what is the inheritance pattern of leprechaunism
autosomal recessive
197
where is the mutation in donotive syndrome and what does it cause
mutation in gene for insulin receptor
defects in insulin binding/insulin receptor signalling
---> severe insulin resistance
198
what are some features of leprechaunism
elfin facial appearance
growth retardation
absence of SC fat
decreased muscle mass
199
what is the inheritance pattern of Rabson Mendenhall syndrome
autosomal recessive
200
what is the issue in rabson mendenhall syndrome
severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia
201
what are some features of RMS
developmental abnormalities
acanthosis nigricans
DKA
202
severe cases of RMS are linked to mutations in what
insulin receptor that reduces sensitivity
203
where are ketone bodies formed and where do they go
liver mitochondria
| diffuse into blood stream and into peripheral tissues
204
what are ketone bodies derived from
acetyl-coA
205
where is acetyl-coA from
beta oxidation of fats / fatty acid oxidation
206
how are ketones used for energy metabolism
converted back to acetyl co-A which enters the TCA cycle
207
how does insulin prevent ketone body overload
prevents lipolysis
208
how does DKA occur in T1DM
if insulin is missed --> break down of fats
209
when might acetyl coA be converted to ketones
if supply of oxaloacetate is limited e.g. no glycolysis
210
why are ketones formed in glucose limiting conditions e.g. DMT1, starvation
increased lipolysis
oxaloacetate used for gluconeogenesis so crebs cycle inhibited
acetyl coA goes to ketones
