exam
Reviewed
anatomy
hypothalamus
area of grey matter in basal forebrain that acts as a major integrative centre for
physiological functions and behaviours
location is ideally positioned to communicate with the periphery, both neurally,
via bidirectional connections with the spinal cord, brain stem autonomic, limbic
and cortical systems, and in an endocrine manner, through circumventricular
organs (such as the median eminence) which have fenestrated endothelia so
lack the typical BBB, allowing exchange of hormones and signalling factors
with the circulatory system
allows it to both receive inputs and coordinate outputs to govern internal
homeostasis in response to changing environments
divided into nuclei with integrative functions to control complex behaviour
patterns:
Function Nuclei Hormones/Peptides
arcuate nuclei (ARC),
Orexigenic (e.g., NPY, AgRP),
ventral medial
Anorexigenic (e.g., POMC, α-MSH);
Feeding/metabolism hypothalamus (VMH),
Peripheral hormone receptors
lateral hypothalamic area
(ghrelin, leptin, insulin)
(LHA)
paraventricular nuclei
Drinking/Electrolyte
(PVN), supraoptic nuclei Vasopressin
and Water Balance
(SON - magnocellular)
preoptic ares (POA) in
GnRH, Oestrogen/Progestin
males, VMH in females,
Sexual Behaviour receptors, kisspeptin/somatostatin
periventricular (ovulatory
(periven)
cyclicity)
Stress Responses PVN (parvicellular) CRH
suprachiasmatic nuclei melatonin release (via pineal gland),
Circadian Rhythms
(SCN) vasopressin, VIP
exam 1
, Milk ejection/uterine
PVN, SON (magnocellular) oxytocin
contractility
Metabolism/thyroid PVN (parvicellular), POA TRH
pituitary
<1g, surrounded by bony sella turcica, essential role demonstrated by smith in
1930s showing its removal in rats led to cessation of growth and lactation,
atrophy of the thyroid, adrenal cortex, and gonads, disturbed salt and water
balance, and metabolic issues, ultimately resulting in death
originates from embryologically distinct ectoderm:
1. posterior (neurohypophysis)
invagination of neural ectoderm of diencephalon
comprised of magnocellular neuronal processes from SON/PVN which secrete
oxy/AVP directly into circulation at pars nervosa
2. anterior (adenohypophysis)
outgrowth of oral ectoderm of buccal cavity
comprised of glandular cells eg. corticotrophes which secrete hormones in
pulsatile manner in response to hypothalamic hypophysiotrophic
neurohormones:
Hypothalamic Hormone
Target
hypophysiotrophic AP Hormone Released by Function
Gland/Organ
neurohormone Target
Body
TSH
TRH (stimulates) Thyroid T3/T4 temperature,
(thyrotrophs)
metabolism
ACTH
CRH (stimulates) Adrenal gland Cortisol Stress
(corticotrophs)
Oestrogen,
FSH, LH
GnRH (stimulates) Gonads progesterone, Reproduction
(gonadotrophs)
etc.
GHRH (stimulates, GH Liver, other Somatomedins Growth,
potentiated by (somatotrophs) tissues (IGF) metabolism
ghrelin) +
exam 2
, somatostatin =
inhibits
Breast
development,
TRH (stimulates) +
Mammary lactation,
dopamine (inhibits, Prolactin NA
glands immune
only non-peptide)
response,
reproduction
neurosecretion
hypothalamo-hypophysial portal system, as demonstrated by Harris’ pituitary
transplantation studies, supplies blood to pituitary via sup/inf hypophyseal
arteries, and allows secretion of hormones into wider circulation via drainage
of portal vessels into venous sinuses
neurotransmitter: AP and depolarisation of nerve terminal triggers Ca influx
and NT vesicular exocytosis into synapse, which acts on neighbouring
neurones
hormone: released from endocrine cell into circulation, transported to distant
target cell
neurohormone (neurosecretion):
1. afferent neural/hormonal stimuli converge via synapse onto neurosecretory
cell (main group in hypothalamus/post pit)
similar structure to other neurones ie axon etc but some morphological
distinctions: in particular lots of rER/golgi/membrane bound granules for
synthesis of peptides > like neurones are also closely supported by glia to
remove excess NT/insulate/regulate excitability (via release of eg. taurine)
2. neurohormone synthesised as inactive precursor polypeptide on rER in cell
body > amino terminal hydrophobic signal peptide allows movement into golgi
> packaged into golgi granules and signal peptide removed (prohormone)
AVP/oxy vesicles also contain neurophysins (carrier proteins to help folding,
also released on exocytosis)
3. transported to terminals by axonal transport, which radiolabelled phosphorus
studies have confirmed occurs ~2-3mm/hr
exam 3
, 4. in terminals co packaged peptidase enzymes in vesicles process to final
secreted peptide/neurohormone (mainly 3-50AA except catecholamines)
evidence = radiolabelled cysteine (component of oxytocin and ADH) injected
into rat cerebral ventricles accumulates quickly in SON/PVN (cell bodies)
before appearing in the pituitary stalk 1-2 hours later (axons) then in posterior
pituitary (terminals) while levels decline in the hypothalamus - whole process
faster if given hypertonic salt solution which stimulates ADH
5. excitation secretion coupling (douglas and poisner): prolonged
AP/depolarisation and larger Ca influx than NT > NH secreted in larger
amounts than NT from larger vesicles (>100nm vs ~50nm) into interstitial
space of neurovascular junction then diffuses into capillaries
evidence = inc electrical stimulation or depolarisation (K⁺ bath) inc ADH
release in rats
evidence of Ca = stimuli that inc hormone output also inc radiolabelled Ca
uptake, and treatments that raise intracellular Ca trigger hormone release,
whereas Ca blockers inhibit secretion
neurosecretory cells may also secrete other peptides to regulate activity in
autocrine/paracrine manner eg. dynorphin from magnocellular helps in
electrical patterning for AVP and inhibits oxy secretion
four different mechanisms of secretion:
1. magnocellular PVN/SON project through PP to secrete oxy/AVP directly into
circulation
2. parvicellular secrete hypothalamic releasing/inhibiting factors from terminals
at median eminence into primary plexus of hypophyseal portal vessels which
stimulates release of hormones from endocrine cells in AP into circulation
3. central sympathetic neurone directly innervates secretory cell (eg. chromaffin
in adrenal medulla) to release hormone (adrenaline) into circulation
4. ganglionic sympathetic neurone directly innervates secretory cell (eg.
pinealocyte) to release hormone (melatonin) into circulation
integration
process by which systems register, transduce and interpret signals from
internal/external environment to direct adaptive changes in prevailing
exam 4
Reviewed
anatomy
hypothalamus
area of grey matter in basal forebrain that acts as a major integrative centre for
physiological functions and behaviours
location is ideally positioned to communicate with the periphery, both neurally,
via bidirectional connections with the spinal cord, brain stem autonomic, limbic
and cortical systems, and in an endocrine manner, through circumventricular
organs (such as the median eminence) which have fenestrated endothelia so
lack the typical BBB, allowing exchange of hormones and signalling factors
with the circulatory system
allows it to both receive inputs and coordinate outputs to govern internal
homeostasis in response to changing environments
divided into nuclei with integrative functions to control complex behaviour
patterns:
Function Nuclei Hormones/Peptides
arcuate nuclei (ARC),
Orexigenic (e.g., NPY, AgRP),
ventral medial
Anorexigenic (e.g., POMC, α-MSH);
Feeding/metabolism hypothalamus (VMH),
Peripheral hormone receptors
lateral hypothalamic area
(ghrelin, leptin, insulin)
(LHA)
paraventricular nuclei
Drinking/Electrolyte
(PVN), supraoptic nuclei Vasopressin
and Water Balance
(SON - magnocellular)
preoptic ares (POA) in
GnRH, Oestrogen/Progestin
males, VMH in females,
Sexual Behaviour receptors, kisspeptin/somatostatin
periventricular (ovulatory
(periven)
cyclicity)
Stress Responses PVN (parvicellular) CRH
suprachiasmatic nuclei melatonin release (via pineal gland),
Circadian Rhythms
(SCN) vasopressin, VIP
exam 1
, Milk ejection/uterine
PVN, SON (magnocellular) oxytocin
contractility
Metabolism/thyroid PVN (parvicellular), POA TRH
pituitary
<1g, surrounded by bony sella turcica, essential role demonstrated by smith in
1930s showing its removal in rats led to cessation of growth and lactation,
atrophy of the thyroid, adrenal cortex, and gonads, disturbed salt and water
balance, and metabolic issues, ultimately resulting in death
originates from embryologically distinct ectoderm:
1. posterior (neurohypophysis)
invagination of neural ectoderm of diencephalon
comprised of magnocellular neuronal processes from SON/PVN which secrete
oxy/AVP directly into circulation at pars nervosa
2. anterior (adenohypophysis)
outgrowth of oral ectoderm of buccal cavity
comprised of glandular cells eg. corticotrophes which secrete hormones in
pulsatile manner in response to hypothalamic hypophysiotrophic
neurohormones:
Hypothalamic Hormone
Target
hypophysiotrophic AP Hormone Released by Function
Gland/Organ
neurohormone Target
Body
TSH
TRH (stimulates) Thyroid T3/T4 temperature,
(thyrotrophs)
metabolism
ACTH
CRH (stimulates) Adrenal gland Cortisol Stress
(corticotrophs)
Oestrogen,
FSH, LH
GnRH (stimulates) Gonads progesterone, Reproduction
(gonadotrophs)
etc.
GHRH (stimulates, GH Liver, other Somatomedins Growth,
potentiated by (somatotrophs) tissues (IGF) metabolism
ghrelin) +
exam 2
, somatostatin =
inhibits
Breast
development,
TRH (stimulates) +
Mammary lactation,
dopamine (inhibits, Prolactin NA
glands immune
only non-peptide)
response,
reproduction
neurosecretion
hypothalamo-hypophysial portal system, as demonstrated by Harris’ pituitary
transplantation studies, supplies blood to pituitary via sup/inf hypophyseal
arteries, and allows secretion of hormones into wider circulation via drainage
of portal vessels into venous sinuses
neurotransmitter: AP and depolarisation of nerve terminal triggers Ca influx
and NT vesicular exocytosis into synapse, which acts on neighbouring
neurones
hormone: released from endocrine cell into circulation, transported to distant
target cell
neurohormone (neurosecretion):
1. afferent neural/hormonal stimuli converge via synapse onto neurosecretory
cell (main group in hypothalamus/post pit)
similar structure to other neurones ie axon etc but some morphological
distinctions: in particular lots of rER/golgi/membrane bound granules for
synthesis of peptides > like neurones are also closely supported by glia to
remove excess NT/insulate/regulate excitability (via release of eg. taurine)
2. neurohormone synthesised as inactive precursor polypeptide on rER in cell
body > amino terminal hydrophobic signal peptide allows movement into golgi
> packaged into golgi granules and signal peptide removed (prohormone)
AVP/oxy vesicles also contain neurophysins (carrier proteins to help folding,
also released on exocytosis)
3. transported to terminals by axonal transport, which radiolabelled phosphorus
studies have confirmed occurs ~2-3mm/hr
exam 3
, 4. in terminals co packaged peptidase enzymes in vesicles process to final
secreted peptide/neurohormone (mainly 3-50AA except catecholamines)
evidence = radiolabelled cysteine (component of oxytocin and ADH) injected
into rat cerebral ventricles accumulates quickly in SON/PVN (cell bodies)
before appearing in the pituitary stalk 1-2 hours later (axons) then in posterior
pituitary (terminals) while levels decline in the hypothalamus - whole process
faster if given hypertonic salt solution which stimulates ADH
5. excitation secretion coupling (douglas and poisner): prolonged
AP/depolarisation and larger Ca influx than NT > NH secreted in larger
amounts than NT from larger vesicles (>100nm vs ~50nm) into interstitial
space of neurovascular junction then diffuses into capillaries
evidence = inc electrical stimulation or depolarisation (K⁺ bath) inc ADH
release in rats
evidence of Ca = stimuli that inc hormone output also inc radiolabelled Ca
uptake, and treatments that raise intracellular Ca trigger hormone release,
whereas Ca blockers inhibit secretion
neurosecretory cells may also secrete other peptides to regulate activity in
autocrine/paracrine manner eg. dynorphin from magnocellular helps in
electrical patterning for AVP and inhibits oxy secretion
four different mechanisms of secretion:
1. magnocellular PVN/SON project through PP to secrete oxy/AVP directly into
circulation
2. parvicellular secrete hypothalamic releasing/inhibiting factors from terminals
at median eminence into primary plexus of hypophyseal portal vessels which
stimulates release of hormones from endocrine cells in AP into circulation
3. central sympathetic neurone directly innervates secretory cell (eg. chromaffin
in adrenal medulla) to release hormone (adrenaline) into circulation
4. ganglionic sympathetic neurone directly innervates secretory cell (eg.
pinealocyte) to release hormone (melatonin) into circulation
integration
process by which systems register, transduce and interpret signals from
internal/external environment to direct adaptive changes in prevailing
exam 4
