Download Pituitary : the master gland Organisation of the pituitary

Pituitary : the master gland
Graduate Entry
y Medicine Year 1
Endocrinology Review
26th May 2011
1. Pituitary gland
2. Thyroid gland
3. Adrenal gland
Pituitary location
and
MRI appearance
Organisation of the pituitary
dura
Pituitary
fossa/sella
Ant
Post
1
Organisation
of the
pituitary
hypothalamus
Anterior pituitary
five endocrine cell
types each secrete
different hormone(s)
‘neurosecretion’
Optic chiasm
cell types can be
differentiated by
antibody labelling and
cell structure
internal carotid
Anterior pituitary
Posterior pituitary
non-secretory
supporting cell type
‘folliculo-stellates’
jugular vein
Feedforward and feedback control
- ve
inhibitory
feedback
Hypothalamus
R l
Releasing
i hormone
h
- ve
Thyroid stimulating hormone (TSH)
feedforward control
Anterior pituitary
Receptors: G protein coupled to cAMP
Actions: in thyroid: stimulates thyroid
production (metabolic
(
rate))
hormone p
Trophic hormone
Endocrine gland
Target
Chemical type: glycoprotein α and β chains
secreted by thyrotroph cells
e.g. cortisol release
from the adrenal
increases iodine uptake by thyroid,
stimulates thyroid growth
2
The hypothalamic-pituitary-thyroid
axis
hypothalamus
cold
Ch i l type:
Chemical
t
polypeptide
l
tid hormone
h
from
f
POMC
precursor, secreted by corticotroph cells
TRH
Inhibitory
feedback
anterior
pituitary
Adrenocorticotrophic hormone
(ACTH)
Released in pulses
Receptor: G protein coupled receptor to cAMP
Actions:
stimulates secretion of cortisol (glucocorticoid
hormone) from adrenal cortex in stress
TSH
thyroid
T3 and T4
Pathology of
TSH secretion is
rare
The hypothalamo-pituitary-adrenal
axis
hypothalamus
Stress
hypoglycaemia
stimulates growth of adrenal cortex
Diurnal rhythm of plasma ACTH
and cortisol
Inhibitory
feedback
anterior
pituitary
ACTH
co
ortisol
CRH
adrenal cortex
glucocorticoids,
cortisol
3
Gonadotrophins: LH and FSH
ACTH pathology
Chemical type: glycoproteins α, β
subunits, from gonadotroph cells
excess ACTH
ACTH, and in turn excess
glucocorticoid, - Cushing's disease
Receptors: G protein coupled to cAMP
Actions: reproductive
deficiency of ACTH, in turn
glucocorticoid deficient- Addison's
disease
Female:
FSH follicle development and ovulation,
LH synthesis of sex steroids by the
ovary
Male:
LH controls testosterone production
FSH stimulates sperm production
Hypothalamo-pituitary-gonadal axis
hypothalamus
GnRH
anterior pituitary
gonadotrophs
-ve
LH + FSH
ovary
estrogen
Pathology of LH and FSH
LH = luteinising
hormone
FSH = follicle
stimulating
hormone
Cyclical release
in menstrual
c cle
cycle
Deficit: infertility in adult life
lack of sexual maturation
Excess: precocious puberty
testes
testosterone
4
Prolactin
Chemical type: Protein hormone
secreted
t d by
b lactotroph
l t t
h cells
ll
Receptor: tyrosine kinase enzyme
-linked
Actions:
stimulates development of breast and milk
production
inhibits reproductive function – lactational
amenorrhaea
Control of prolactin release
Control of prolactin release
hypothalamus
suckling +ve
dopamine -ve
anterior pituitary
lactotrophs
PRL
Breast growth and milk production
Prolactin pathology
PRL release is increased by
suckling and stress
Too much PRL secretion
the only pituitary hormone
whose principal control is
inhibitory
by prolactin secreting pituitary tumours
- prolactinomas
Dopamine agonists e.g.
b
bromocryptine,
ti
suppress
lactation
causes galactorrhoea, infertility,
impotence in men
PRL production is
stimulated by estrogen
during pregnancy
5
Growth hormone
Growth hormone axis
Hypothalamus
Chemical type: Protein hormone
secreted by somatotroph cells
GHRH
Anterior pituitary
somatotrophs
Receptor: enzyme-linked
Actions:
stimulates long bone and tissue growth
direct and indirect actions via IGF’s
stimulates protein synthesis
raises blood glucose
GH pathology
Gigantism due to excess
GH secretion
Short stature if lack GH
nb if prior to epiphyseal
plate fusion at puberty
Acromegaly: excess GH
secretion after
pp y
plates
p
epiphyseal
have fused
Enlargement of hands
and feet, Coarsening
of facial features,
Weight gain
Li
Liver
GH -ve
GH
IGFs
Long bone and muscle growth
Posterior pituitary
Formed by axons and terminals of
h
hypothalamic
th l i neurosecretory
t
neurons
Secretes peptide hormones antidiuretic hormone (ADH, also known
as vasopressin) and oxytocin
The hormones are made in the
hypothalamus
6
Stimulation of posterior pituitary
hormone release
Stimuli of ADH release
Plasma osmolality
Blood volume
hypothalamus
Stimulus
depolarises
neuron
axon
Ca2+
posterior
pituitary
action potential
exocytosis
osmotic osmoreceptors detect ↑ plasma osmotic pressure
and stimulate release. Vascular baroreceptors stimulate
release when they detect ↓ in blood pressure
Oxytocin
Diabetes insipidus
Chemical nature: peptide
Too little ADH
Receptors: PLC-coupled
Two types:
hypothalamic: lack
of ADH production
renal: lack of ADH
action
Actions:
contraction of uterine
muscle
l in
i childbirth
hildbi th
milk ejection by contraction
of breast myoepithelium
7
Control of oxytocin release
stretch of cervix/vagina at parturition
suckling – nipple stimulation causes
milk-ejection reflex
Pituitary tumours
hormonal effects: hormone-secreting tumours
effects depend on cell type
mechanical effects: affects vision as presses on
optic chiasm
Pathology
deficit may cause prolonged labour
knockout mice labour normal but no
milk-ejection
Normal
Adenoma
Anatomy of the Thyroid
The Thyroid Gland
8
Thyroid structure
Thyroid hormones
the thyroid
y
p
produces two unique
q hormones:
tri-iodothyronine (T3) and thyroxine (T4)
T3 and T4 are the only iodine containing
hormones in vertebrates
the only source of iodide is dietary (veg, fish,
salt)
iodide is scarce and insufficient supply is a
major health problem in many parts of the world
Regulation of thyroid hormone
secretion
Hypothalamus
TRH
Peripheral metabolism of T4
stimuli
e g cold
e.g.cold,
glucose
Anterior
pituitary
Inhibitory
feedback
TSH
Thyroid
T3 and T4
metabolism
iodothyronines are unusual in that the main
thyroid product (T4) is not the active hormone (T3)
metabolism T4 to T3 occurs in the liver and kidney
T4 is converted to T3 by Type I deiodinase
9
Thyroid Receptor action
Hyperthyroidism – ‘thyrotoxicosis’
restless, anxiety
TR in
i th
the
nucleus bind
DNA and
activate
transcription
Timescale
- hours
exophthalmos
- eyes protrude
goitre
tachycardia
and rapid
pulse
lose weight
despite
normal
appetite
intolerance
of heat
hot hands
High T4
Low TSH
metabolic
effects
exacerbate
diabetes
mellitus
diarrhoea
hand
tremor
Hyperthyroidism
Most common cause is Graves’ disease
Hypothyroidism
Due to autoimmune production of antibody to the
TSH receptor which acts like a superactive TSH
cretinism in young
young, myxoedema in adult
failure of production by thyroid (‘burned-out’
Grave’s disease)
failure of pituitary or hypothalamus to produce
TSH or TRH
thyroid hormone resistance – inactivating
mutation of thyroid hormone receptor
10
Hypothyroidism
Low T4
High TSH
Prenatal thyroid
deficiency (cretinism)
apathy, tired
goitre
i
heart slowing
and slow
pulse
poor neural
d
development
l
t
stunted growth
muscle
weakness
weight gain
constipation
intolerance
of cold
muscle
weakness
treated by giving
thyroid hormone
at birth
cold hands
Calcitonin
Drugs affecting the Thyroid
• prevention of hypercalcaemia
• no long term effect on serum Ca22+
Thyroxine (T4) is given for
h
hypothyroidism
th
idi
• effects are over-ridden by PTH if in excess; CT
receptor downregulation
iodine: in large doses reduces the
activity of the gland in hyperthyroidism
Bone inhibits osteoclast breakdown of bone
Gut helps control rise in Ca2+ due to meals,
inhibits absorption
radioactive iodine can be given to
destroy thyroid tissue
beta blockers used to alleviate
symptoms in acute control of
thyrotoxicosis
11
Stress: a change that disturbs or
threatens to disturb homeostasis
The Adrenal Gland
Acute stressors
Trauma
Infection
Intense heat or cold
Starvation
Surgery
Severe blood loss
Pain
Dehydration
Chronic stressors
Anxiety
Depression
Adrenal structure
Cortex
Innervation of the adrenal gland
adrenaline
noradrenaline
Medulla
12
Sympathetic activity in stress
Rapid increase in
adrenaline and
noradrenaline in
stress
Preparation for emergency activity
very rapid increase
and then rapid
decrease
depletes only a
small fraction of
the stored
catecholamine
The adrenal cortex
Maintenance of essential processes in chronic stress
medulla
cortex
Control of cortisol production
Hypothalamus
capsule
stress
CRF
Inhibitory
feedback
zona reticularis
androgens
zona fasciculata
cortisol
zona glomerulosa
aldosterone
Anterior
pituitary
ACTH
Adrenal
Receptors
intracellular
-GR
glucocorticoids
cortisol
13
Glucocorticoids
preserve glucose for the brain
Glucocorticoids also act on
accelerate gluconeogenesis in liver
central nervous system activity
accelerate lipid and protein catabolism
in liver and peripheral tissues
(appetite, mood)
increased red blood cell production
maintenance of circulation
reduce inflammation and the immune
response- prevent it from becoming
disruptive
-
Stress inhibits reproduction
Clinical uses of glucocorticoids
Hypothalamus
Synthetic glucocorticoids eg prednisone
GnRH
glucocorticoids
-ve
Anterior pituitary
PRL
LH and FSH
reproduction and lactation
anti-inflammatory
ti i fl
t
therapy
th
in
i
e.g. asthma, arthritis
used topically in inflammation
of skin, eye or ear
prevent graft rejection in
transplantation
avoids risk of pregnancy - a drain on resources
14
Cushing’s disease
‘buffalo
hump’ fat
pads
moon face
bruising
thin skin
hypertension
thin arms
and legs
trunkal obesity
osteoporosis
infertility
poor wound healing
Aldosterone
Chronic stress and illness
In utero
stress of undernourishment or poor
oxygen results
lt iin llow bi
birth
th weight
i ht and
d
is associated with hypertension,
diabetes mellitus, lower life
expectancy when adult
Childhood
chronic stress > retarded growth
Adults
continuing psychological stress is a
major factor in ‘stress illnesses’
The renin-angiotensin system
‘mineralocorticoid’
regulates body sodium and fluid volume
acts via nuclear mineralocorticoid receptors
(MR)
stimulates reabsorption of Na+ in the kidney
in exchange for K+
(cortisol also binds MR)
15
Addisons disease
- adrenal insufficiency
Mineralocorticoid dysfunction
Hypoaldosteronism
H
ld t
i
- sodium
di
loss,
l
low
l
blood volume, low blood pressure
Lack of
aldosterone and
cortisol
Hyperaldosteronism - excess sodium
retention, water retention, increased blood
pressure
Pigmentation
results from
high circulating
levels of
Melanocyte
stimulating
hormone (MSH)
Spironolactone – a MR antagonist is a diuretic
drug used as an anti-hypertensive
Low blood
pressure
Addisons disease
pigmentation
Addisons disease
pigmentation
hypothalamus
hypothalamus
CRH
CRH
no
feedback
anterior pituitary
Inhibitory
feedback
anterior pituitary
POMC
ACTH
adrenal cortex
cortisol
POMC
MSH
ACTH
skin melanocytes
pigmentation
MSH
skin melanocytes
Melanocortin receptor
pigmentation
16
Any questions:
[email protected]
To see slides in more detail see weblearn.
You may find BM1 teaching materials
helpful, see Organisation of the Body
y Term ‘Endocrinology’
gy p
pages
g on
Hilary
weblearn.
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