Neuroendocrine Systems

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Neuroendocrine Systems
hypothalamus receives inputs from essentially
all homeostatic functions uses neurotransmitters
and endocrine hormones to respond to
changes neuroendocrine neurons release
transmitters into the bloodstream rather than
synapses anterior pituitary gland is a major
target of neuronhormones releasing/inhibiting
hormones travel through the portal capillary
plexus even though it's blood, there is
effectively a direct connection hypothalamus
directly enervates the posterior pituitary cells
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Hypothalamic Hormones and their Targets
pituitary hormones are divided into 5 axes, or
areas of effect anterior pituitary cells have
1 hormone receptor each cell then releases
a 2nd hormone into general circulation axes
themselves have crosstalk and feedback between
systems pituitary hormones then cause other
glands to release tertiary hormones which
feed back on the hypothalamus and pituitary
glands
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Hypothalamic Hormones and their Targets
neurohormones are released according to various
rhythmic patterns pulses of hypothalamic
hormones induce pulses of pituitary ones
continuous release generally induces
desensitization and tolerance ultradian/circhoral
every hour or 2 circadian/diurnal every 24
hours diurnal light/dark cycle circadian is
actual timing directed by the hypothalamic
suprachiasmatic nucleus both of the above can be
superimposed on the other-- both patterns
active also includes seasonal/monthly
variations, particularly reproduction
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Brain-Pituitary-Thyroid Axis
controls metabolism primarily hypothalamus
secretes thyrotropin releasing hormone
(TRH) stimulates thyrotropic cells of the
pituitary to secrete thyroid stimulating
hormone (TSH) thyroid releases thyroxine (T4)
and triiodothyronine (T3) T4 and T3 feedback
onto hypothalamus most T3 and T4 are bound to
proteins in blood less than 1 thyroid hormones
are unbound
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Brain-Pituitary-Thyroid Axis
T3 and T4 are critical for metabolism during
development and adults thyroid hormones require
iodine and are lipid-like molecules work
through steroid receptor superfamily binds in
cytoplasm, imported to nucleus and works as a
transcription factor hyperthyroidism causes
tremors, insomnia, or nervousness up to
seizure/coma thyroid deficiency causes
hypothermia, cerebellar ataxia, behavioral
problems fetuses/early neonatal lack of thyroid
hormones causes cretinism
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Growth the Somatotropic Axis
hypothalamic hormones growth hormone releasing
hormone (GHRH) and somatostatin (inhibits
growth hormone) pituitary secretes growth
hormone (GH) or somatotropin made by
somatotropes (30 of pituitary cells) somatotropi
n induces liver to make insulin-like growth
factor 1 (IGF-1) GH and IGF-1 work
synergistically or independently to cause
growth GH feedback increases somatostatin
synthesis IGF-1 affects GHRH
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Growth the Somatotropic Axis
growth hormone is essential for neonatal and
puberty growth spurts lack of GH (or IGF-1)
causes dwarfism GH effects are often sexually
dimorphic, uses different growth targets GH
receptor is a tyrosine kinase receptor
activating the JAK/STAT pathway GH binds an
alternatively spliced secreted receptor
isoform in the blood to aid circulation and
half life IGF-1 also uses a tyrosine kinase
receptor but is linked to the MAP kinase
pathway
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Stress Brain-Pituitary-Adrenal Axis
hypothalamus releases corticotropin releasing
hormone (CRH) and argenine vasopressin
(AVP) CRH AVP stimulates corticotropes in the
pituitary to make adrenocorticotropic hormone
(ACTH) ACTH circulates in the blood to release
glucocorticoids (which negatively regulate
CRH and ACTH) glucocorticoids regulate glycogen
synthesis, blood flow, heart rate as well as
immune system function and inhibits inflammatory
response glucocorticicoids are steroids made
from cholesterol like mineralocorticoids work
through steroid receptors (like thyroid
hormone)
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Stress Brain-Pituitary-Adrenal Axis
chronic exposure to high corticosteroids results
in brain damage and neurodegeneration,
particularly in the hippocampus lack of
corticosteroids causes cell loss in dentate
gyrus granule cells stress causes a rapid
increase in axis activity, and negative
feedback causes a rapid decrease in activity
this axis works in a burst of activity chronic
stress can cause immune problems, although
people can adapt to higher basal levels of
stress
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Reproduction Brain-Pituitary-Gonad Axis
hypothalamus releases gonadotropin (lutinizing)
releasing hormone (GnRH or LRH) pituitary
releases lutinizing hormone (LH) and follicle
stimulating hormone (FSH) from
gonadotropes testes or ovaries respond producing
androgens, estrogen and progestins all 3 are
made by both testes and ovaries only quantities
differ reproductive axis is active during
development setting up the sex organs then is
essentially quiescent until puberty sexual
dimorphism causes males and females to release
GnRH differently seasonal breeders have long
cycles separate from circadian/ultradian
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Reproduction Brain-Pituitary-Gonad Axis
LH and FSH work in both males and females
required for maturation of ovaries and
spermatogenesis/steroidogenesis same receptors
working with a sex-specific transcription
factor all sex steroid hormones work through
the steroid receptor superfamily bind in the
cytoplasm and move to nucleus for their
particular promoter, often working as
heterodimers negative feedback inhibits
secretion in both the hypothalamus GnRH and
LH/FSH in the pituitary of males females alter
the GnRH feedback during estrus, making it
reinforcing
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Lactation and Lactotrophic Axis
prolactin is secreted from the pituitary to
stimulate milk production unlike the others,
no hypothalamus peptides seem to be involved
dopamine appears to inhibit prolactin production
in lactotropes prolactin works with oxytocin to
maintain lactation works to grow and increase
mammary tissue, stimulating casein mRNA also
increases the effectiveness of LH on the corpus
luteum prolactin is related to growth hormone
and also has many receptor isoforms in the
tyrosine kinase family
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Hypothalamic Posterior Pituitary Hormones
arginine vasopressin (AVP) and oxytocin (OT)
neuropeptides activate the posterior pituitary
(hypophyseal) cells AVP regulates osmolarity of
the system ie. water-salt balance affects the
kidneys and drinking desire to control
concentrations oxytocin regulates lactation and
uterine contraction both also regulate
reproductive social behaviors mutation of AVP
receptor V1b causes social aggression
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Brain Sexual Dimorphisms
sexual dimorphism starts in late prenatal/
neonatal mammals referred to as organizational
effects (mostly through androgens) puberty
activational effects require the previous
organizational effects several regions of the
brain in both rats and humans are
dimorphic INAH-3 (interstitial nucleus of the
hypothalamus) is reported to be largest in
males, intermediate in homosexuals, smallest
in females hippocampus, neocortex and amygdala
all differ in size and neurochemistry
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Brain Sexual Dimorphisms
male and female sexual behaviors are different
and are driven by organizational changes in
hypothalamus hormones and responses
artificially giving the other sex hormone does
not mimic the response in males, the preoptic
area rostral to the hypothalamus controls sex
behaviors in females, the ventromedial
nucleus of the hypothalamus exerts
control pheromones are secreted in vaginal or
sebaceous glands in some animals work through
the vomeronasal organ to olfactory bulb and
eventually to the preoptic nucleus and
hypothalamus