48544
The hypothalamus and
anterior pituitary
- The hypothalamus and anterior pituitary
- Recognises external and internal stimuli and
stimulates an appropriate bodily response
- Stimuli; cold, stress, metabolic demand,
dehydration, exercise, time, mestrual cycle, sleep,
breastfeeding, puberty, pregnancy/menstrual cycle
- Responses; adrenal/thyroid/gonadal
function, lactation, growth, osmoregulation,
parturition and metabolism
- Responses; adrenal/thyroid/gonadal
function, lactation, growth, osmoregulation,
parturition and metabolism
- Stimuli; cold, stress, metabolic demand,
dehydration, exercise, time, mestrual cycle, sleep,
breastfeeding, puberty, pregnancy/menstrual cycle
- Structure and connections
- Hypothalamus
- Part of the brain (below the thalamus) -
major coordination centre for stimuli
- Part of the brain (below the thalamus) -
major coordination centre for stimuli
- Anterior pituitary
- Not part of the brain (embryoinically
derived from the oral actoderm)
- Lies in the pituitary fossa of the sphenoid
bone - if it grows it presses n the optic chiasm
(visual disturbances seen in pituitary tumours)
- Not neurally connected to the brain
- Instead nuclei within the hypothalamus detect
a stimulus produce an appropriate releasing
hormone (e.g. CRH, TRH, GnRH etc.)
- These hormone producing neurnes secrete the releasing hormone
into a network of cappillaries (neurocrine) called the portal system
- From here the releasing hormones travel in the blood
to the hormone producing cells of the anterio pituitary
- Releasing hormones stimulate secretion of tropic
hormones into a second capillary network which
carries the hormones to their target tissues
- Releasing hormones stimulate secretion of tropic
hormones into a second capillary network which
carries the hormones to their target tissues
- From here the releasing hormones travel in the blood
to the hormone producing cells of the anterio pituitary
- These hormone producing neurnes secrete the releasing hormone
into a network of cappillaries (neurocrine) called the portal system
- The posterior pituitary develops from
the brain and is connected neurally
- Instead nuclei within the hypothalamus detect
a stimulus produce an appropriate releasing
hormone (e.g. CRH, TRH, GnRH etc.)
- Not part of the brain (embryoinically
derived from the oral actoderm)
- Hypothalamus
- Recognises external and internal stimuli and
stimulates an appropriate bodily response
- Anterior pituitary hormones
- Three major families of hormone are produced here
- POMC family - ACTH (and MSH)
- Produced by corticotrophs (basophil)
- Produced by corticotrophs (basophil)
- Glycoprotein family - TSH, FSH, LH (hCG)
- TSH: thyrotrophs (basophil)
- FSH and LH: gonadotrophs (basophil)
- TSH: thyrotrophs (basophil)
- Somatotropic family - GH and prolactin
- GH: somatotroph (acidophil)
- PRL: lactotroph (acidophil)
- GH: somatotroph (acidophil)
- POMC family - ACTH (and MSH)
- All are regulated by hormones secrted by
the hypothalamus into the protal system
- = hypothalamic releasing hormones
and release-inhibiting factors
- Corticotropin releasing hormone (CRH)
- Stimulates ACTH release
- Stimulates ACTH release
- Thyrotropin releasing hormone (TRH)
- Stimulates TSH release
- Stimulates TSH release
- Gonadotropin releasing hormone (GnRH)
- Stimulates FSH and LH secretion
- Stimulates FSH and LH secretion
- Growth hormone releasing hormone (GHRH)
- Stimulates GH release
- Stimulates GH release
- Somatostatin
- Inhibits GH secretion
- Inhibits GH secretion
- Dopamine (prolactin inhibitory factor, PIF)
- Inhibits PRL secretion
- Inhibits PRL secretion
- Corticotropin releasing hormone (CRH)
- = hypothalamic releasing hormones
and release-inhibiting factors
- Three major families of hormone are produced here
- Endocrine axes
- E.g. Hypothalamo-pituitary-thyroid axis
- Metabolic demand detected in hypothalamus -> secretes TRH
- TRH acts on thyrotrophs in the ant. pituitary -> TSH secretion
- TSH acts on follicular cells in the thyroid -> secrete T4 and active T3
- T3 acts on target cells to increase metabolism
- -
- -
- T4 can be converted to active
T3 in the peripheral tissues
- +
- +
- T3 and T4 negatively feedback
on the hypothalamus and ant.
pituitary
- -
- -
- -
- T3 acts on target cells to increase metabolism
- TSH acts on follicular cells in the thyroid -> secrete T4 and active T3
- TRH acts on thyrotrophs in the ant. pituitary -> TSH secretion
- Metabolic demand detected in hypothalamus -> secretes TRH
- Axes;
hypothalamo-pituitary-thyrod/ganadal/adrenal axes
and; the GH-IGF axis
- E.g. Hypothalamo-pituitary-thyroid axis
- Prolactin
- Acts on mammary tissues to
stimulate breast development
and increase milk production
- There is no end product from this system
to feedback and inhibit PRL secretion
- Instead PRL is constituitively prodcued by
lactotrophs and constantly ready to be secreted
- To regulate this pathway dopamine (prolactin
inhibitory factor, PIF) is constantly being secreted
when there is no requirement for milk production
- To regulate this pathway dopamine (prolactin
inhibitory factor, PIF) is constantly being secreted
when there is no requirement for milk production
- Instead PRL is constituitively prodcued by
lactotrophs and constantly ready to be secreted
- There is no end product from this system
to feedback and inhibit PRL secretion
- Regulation
- Hypothalamus:
Dopamine constantly
secreted
- Lactotrope: Constitutive PRL secretion
- Breast tissue: milk production
- +
- -
- Dopamine agonists
(e.g. Bromocriptine -
parkinson's drug)
- Used in prolactinomas (PRL
secreting tumours - the most
common pituitary tumour)
- Used in prolactinomas (PRL
secreting tumours - the most
common pituitary tumour)
- Dopamine agonists
(e.g. Bromocriptine -
parkinson's drug)
- Breast tissue: milk production
- -
- -
- Nipple stimulation
(during suckling)
- Nipple stimulation
(during suckling)
- -
- Stress
- Stress
- -
- Dopamine antagonists
(e.g. Chlopromazine -
antipsychotic)
- +
- +
- Dopamine antagonists
(e.g. Chlopromazine -
antipsychotic)
- Lactotrope: Constitutive PRL secretion
- Hypothalamus:
Dopamine constantly
secreted
- Acts on mammary tissues to
stimulate breast development
and increase milk production
- GH
- Secretion of GH is under dual
control from the hypothalamus
- Stimulatory: GHRH
- Inhibitory: Somatostatin (GHIH)
- Both secretiong control hormones
act together to regulate GH levels
- There is also some negative
feedback from IGF-1 (secreted
by the liver and bone in
response to GH) and by an
elevation in blood glucose
- GH causes an increase
in blood glucose
- GH causes an increase
in blood glucose
- Stimulatory: GHRH
- GH-IGF axis
- Hypothalamus: GHRH
- Ant. Pituitary (somatotroph): GH secretion
- Bone: IGF-1 secretion
- IGF-1 promotes linear bone growth
- IGF-1 promotes linear bone growth
- Liver: IGF-1 secretion,
reduced glucose uptake
and gluconeogenesis
- Tissue growth (e.g. muscle)
- -
- IGF-1 and
increased blood
glucose
- IGF-1 and
increased blood
glucose
- Tissue growth (e.g. muscle)
- Bone: IGF-1 secretion
- +
- +
- Exercise, sleep,
stress, hypoglycaemia
- Exercise, sleep,
stress, hypoglycaemia
- Ant. Pituitary (somatotroph): GH secretion
- Hypothalamus: somatostatin
- -
- -
- Hypothalamus: GHRH
- Actions
- Mobilises fat stores
- Opposes insulin and increases blood glucose
- Stimulates tissue growth (muscle
and bone) through IGF-1
- IGF-1
- Stimulates growth by....
- Increasing amino acid uptake
- Promoting protein
synthesis in muscle
and cartilage
- Increasing amino acid uptake
- Stimulates growth by....
- GH is responsible for
the linear growth during
childhood and puberty
- IGF-1
- Mobilises fat stores
- Excess
- In childhood = gigantism
- Excess long bone
growth before puberty
- Excess long bone
growth before puberty
- In adulthood = acromegaly
- Large; hands, feet, jaw, brow, internal
organs; cardiovascular problems, joint
pains and glucose intolerance
- Large; hands, feet, jaw, brow, internal
organs; cardiovascular problems, joint
pains and glucose intolerance
- Testing levels
- In general
- Endocrine disorders can be...
- Primary (gland disorder)
- Secondary (pituitary disroder)
- Or tertiary (hypothalamus disorder)
- Primary (gland disorder)
- Testing of an endocrine axis
is important to detemine
where the defect is
- Also to monitor the disorder
- Also to monitor the disorder
- Endocrine disorders can be...
- GH
- When to take the sample?
- GH secretion is episodic and daily levels change
- Etherefore something called dynamic testing is done
- Dynamic testing
- The idea: to challenge the axis and
see if the appropriate change occurs
- Excess GH
- Give IV glucose (take
GH level before)
- After 1hr check
GH level again
- GH should have
decreased (unless it is
being overproduced)
- GH should have
decreased (unless it is
being overproduced)
- After 1hr check
GH level again
- Give IV glucose (take
GH level before)
- Deficiency
(dwarfism)
- Have patient
excercise (after
fasting) - take GH
measurement first
- After 1hr check
GH level again
- GH should have
increased (unless
deficient)
- GH should have
increased (unless
deficient)
- After 1hr check
GH level again
- Have patient
excercise (after
fasting) - take GH
measurement first
- Excess GH
- The idea: to challenge the axis and
see if the appropriate change occurs
- Dynamic testing
- Etherefore something called dynamic testing is done
- GH secretion is episodic and daily levels change
- Commercial kits available
- When to take the sample?
- In general
- In childhood = gigantism
- Secretion of GH is under dual
control from the hypothalamus
- Effects of hypophysectomy (loss
or removal of anterior pituitary)
- Atrophy and functional loss of
gonads, thyroid and adrenals
- Can be treated with hormone
replacement therapy (TSH, ACTH, sex
steroids and maybe GH, FSH and LH)
- Can be treated with hormone
replacement therapy (TSH, ACTH, sex
steroids and maybe GH, FSH and LH)
- Signs and symptoms
- Loss of libido and depression
- Failure of beard growth
- Hypotension
- Hypoglycaemia
- Testicular atrophy
- Muscle weakness
- Loss of libido and depression
- Atrophy and functional loss of
gonads, thyroid and adrenals
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