Transcript Endocrine Hypothalamus

Chapter 6, The Endocrine
Hypothalamus
Small bit about the pituitary

Pituitary thought to be the “master gland”
 Integral
in a variety of responses
 Remove it and see atrophy of these responses
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However studies of removal and re-implantation (at other
locations) do not support level of importance
Studies that block pituitary-hypothalamic association
demonstrate importance of hypothalamus
 Additional
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lesion studies reinforce this importance
Hypothalamus is going to act as a ‘go-between’ for
incorporating neural inputs and hormone responses
General information on hypothalamus
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Hypothalamus a cluster of nerve nuclei
 Groupings
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Neurosecretory cells
 Secrete
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cAMP levels will be up-regulated, actions activated
Prime target tissue (but not only) – the pituitary
 Anterior

both inhibitory and stimulatory hormones
Hypothalamic hormone products are all protein hormones
Receptors in anterior pituitary all G-protein coupled

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of neurons
and posterior pituitary differ a bit (more in future chapters)
Receptors for hypothalamic hormones can exist outside the pituitary
 Gonadotropin
releasing hormone (GnRH) receptors on ovary
Hypothalamus – chemical messengers
Hypothalamus
Hypothalamus

Hypothalamus basal part of the diencephalon lying
below the thalamus
Forms
walls and floor of third ventricle
Includes optic chiasma, tuber cinereum, infundibulum, and
mammillary bodies
Lower part of tuber cinereum is the median eminence
 Median
eminence links to anterior pituitary via hypophysial portal
system
In
humans - ~2.5cm long, ~4g in weight
SON and PVN comprise magnocellular
system
Parvocellular system
Control of hypothalamic function

Hypothalamus regulated by internal hormonal signals & neural
inputs from other sources (many cases outside of organism)
 Final
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Involved in non-endocrine functions
 Food

common pathway for signals to reach pituitary
intake, (this has impact on GH secretion, but indirectly)
Feedback mechanisms in conjunction with pituitary
 Short-,

long-loops, auto-feedback
Rhythmic secretion of hormones and activity

Circadian rhythms, suprachiasmatic nuclei = clock?
Feedback loops
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Short and long
loop feedback
systems mostly
defined by how
many steps
involved
Autoinhibition is a
way for
endocrine tissues
to fine-tune their
production
Hypothalamus-pituitary association & feedback
Alternate view
Need to start thinking in
layers.
Keep in mind long-loop,
short-loop, and auto-inhibition
are happening
simultaneously.
It is not a system with
particular order and no one
aspect of feedback trumps
any other.
Hypothalamic hormones

Some of the major hypothalamic hormones (there are more!)
 Corticotropin-releasing
hormone (CRH)
 Gonadotropin-releasing hormone (GnRH)
 Gonadotropin-inhibiting hormone (GnIH)
 Growth hormone releasing hormone (GHRH)
 Growth hormone release-inhibiting hormone (AKA Somatostatin)
 Prolactin releasing hormone (PRH)
 Prolactin releasing-inhibiting hormone (AKA Dopamine)
 Thyrotropin-releasing hormone (TRH)
 MSH release-inhibiting hormone (Also Dopamine)
Thyrotropin-releasing hormone (TRH)
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Will induce thyroid stimulating hormone (TSH) and prolactin release
from pituitary
Produced in paraventricular nuclei & preoptic area
Small active hormone
 Larger
pro-TRH molecule yields several TRHs
 Notable in that it has no free N-terminal amino group

TRH found in many other species
Ultimately this hormone is going to initiate a path of response that activates the
thyroid gland, this is an important structure
 Conservation among species
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Somatostatin (SST)
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Inhibits growth hormone (GH) release from the anterior pituitary
 AKA:
Growth hormone release-inhibiting hormone
 Also inhibits thyroid stimulating hormone (TSH) secretion
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Produced in anterior periventricular region
Also secreted from CNS, gut, and pancreas
 Inhibits
glucagon, gastrin, insulin, & secretin
Growth hormone releasing hormone (GHRH)
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Now also termed somatocrinin
Induces growth hormone release from the anterior pituitary
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Similar sequences to several gut peptides
Produced from arcuate nuclei & ventromedia nuclei
Long half-life of 50 min.
Variable release over multiple time scales
Ghrelin – also induces GH release, and influences hunger

Important to note the linking between hormones that influence hunger and
one that influences growth
Gonadotropin-releasing hormone (GnRH)
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Induces follicle stimulating hormone (FSH) and luteinizing hormone
(LH) release from anterior pituitary
 Release
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is pulsatile and this is important to what hormone is induced
Produced from preoptic area and suprachiasmatic nucleus
Receptors in tissues other than brain, use in rest of body also
unclear
 Found
on ovary in some animals
 Local
 Found
 Set
regulation of estrogen production perhaps
in the uterus of mammals
up for response during pregnancy?
 Local regulation of tissue responses in preparation for pregnancy?
Gonadotropin-releasing hormone (GnRH)

15 different varieties
have been described
vertebrates
Genes for variants on
multiple chromosomes
 Sequence highly
conserved
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Most spp. have 2+
types, uses unclear
Gonadotropin-inhibiting hormone (GnIH)
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Newer hypothalamic hormone – first described 2000
 Mammalian
version also called RFamide-related peptide-3 (RFRP-
3)
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Produced by the paraventricular nuclei
Inhibits luteinizing hormone (LH) release, unclear about follicle
stimulating hormone (FSH)
 Works
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with GnRH to control pulsatile LH release
GnIH secreting neurons found outside hypothalamus, may
influence other neural and physiological processes
GnIH release influenced by stress, developmental state, and
photoperiod
Corticotropin-releasing hormone (CRH)
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Induces adrenocorticotropic hormone (ACTH) and β-endorphin
release from the anterior pituitary
From parvocellular region of paraventricular nuclei
41 amino acids

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Highly conserved across species, again, may not want to mess up the
response generated here
Long half life – 60 min.
Dopamine
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Dopamine found in hypophysial portal system
 Released
from arcuate nuclei
 Remember it can also be a neurotransmitter
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Acts as a prolactin-release-inhibiting factor (PIF)
 Prolactin
may be continually released unless inhibited
 Experiments in vitro show dopamine inhibits
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Dopamine also appears to function as melanotropin-release
inhibitory factor

Not clear of the use of this in humans
Prolactin-releasing hormone
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Questionable as to what this hormone is
TRH,
vasoactive intestinal polypeptide (VIP), or oxytocin all
candidates
Orphan receptor identified as PRH receptor
Evidence that whatever it is it’s coming from the paraventricular
nuclei
Nursing can induce prolactin release, but the physical act
may be a block on dopamine production
 Prolactin is an old hormone with extensive exaptation,
control of it may be complex due to this
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Hypothalamic disorders
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Tumors, trauma, infections, congenital deformations, genetic defects,
& vascular alterations
 Can
affect secretion selectively or collectively
 Usually leads to decreased pituitary function

Deficits in individual hormones
 Hypothalamic
hypothyroidism – TRH deficient
 Olfactory-genital dysplasia – GnRH deficient

Kallmann’s Syndrome