week 3, lecture 1 Flashcards
what regions in the 3rd ventricle allow selective passage of signals from the blood into the hypothalamus called?
circumventricular organs via ventricular fluid
what signals can the hypothalamus sense from the bloodstream?
Can sense osmolarity, glucose, signal peptides (short loop feedback, appetite mediators)… many
what areas does the hypothalamus communicate with?
brainstem, limbic areas, and cortex
what are the 2 types of neurons in the hypothalamus
magnocellular and parvocellular neruons
where are magnocellular neurons located
supraoptic and paraventricular nuclei
SON & PVN
where are parvocellular neurons located
many different nuclei
which are large or small; magnocellular vs parvocellular
magno= make large quantities of neurohormones
parvocellular= small
what neurohormones are in the magnocellular neurons?
oxytocin and vasopressin
what neurohormones are in parvocellular neurons of the hypothalamus
CRH, TRH, GHRH, GHIH, DA, GnRH/LHRH, PRH
–> i.e. oxytocin and vasopressin are magnocellular and everything else is parvocellualr
what is the output of the magnocellular neurons
posterior pituitary – release neurohormones into systemic circulation
what is the output of the parvocellular neurons
median eminence (portal vein towards anterior pituitary), brainstem, spinal cord
what is the hypothalamic- pituitary system? where does the signals first go?
go to anterior pituitary
The hypothalamus secretes releasing or inhibiting hormones into 1st set of capillaries
These travel down to the anterior pituitary and modulate hormone secretion from those cells
Anterior pituitary hormones control several other endocrine glands
–Thyroid, adrenal gland, gonads, liver
magnocellular vs parvocellular for anterior or posterior pituitary
magno= posterior
parvo= anterior
slide 9 chart
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posterior pituitary composed of?
Composed of axon terminals of magnocellular neurons and arteries forming inferior hypophyseal artery
anterior pituiaary is composed of?
Composed of endocrine tissues
(responsible for producing ACTH, GH, TSH, etc.)
what inputs foes the anterior pituairaty get
eceives hypothalamic neurohormones via the secondary capillary plexus that receives blood from portal vein (hypothalamic parvocellular neurons release hormones into the primary capillary plexus within median eminence)
Superior hypophyseal artery –>primary capillary plexus –> portal vein–> secondary capillary plexus
where does anterior pituitary release hormones to?
Releases hormones into the hypophyseal veins (into systemic circulation via internal jugular vein)
where does hypothalamus receive input from
Receives input from: CNS, intestines, heart, liver, stomach
Contain specialized neurons that are able to detect different senses: glucose-sensing neurons, osmoreceptors
positive and negative feedback loops in hypothalamus
Various hormones and signals from periphery can regulate hypothalamus via positive and negative feedback loops
Negative loop: CRH stimulates ACTH release from anterior pituitary, ACTH inhibits hypothalamus from releasing more CRH
Positive loop: Oxytocin stimulates uterine contractions, fetal head descends and stretches the cervix, triggering hypothalamus to release more oxytocin
what is the majority of feedback loops in hypothalamus
negative feedback
i.e. homeostatic or nonhomeo
long loop of hypothlamus and pituitary
target endocrine gland –> hypothalamus or pituitary
short loop of hypothalamus and pituitary
anterior pituitary –> hypothlamus
slide 13 chart
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where is growth hormone made and by what?
Produced by somatotrophs within the anterior pituitary
how is growth hormone released
Released in pulsatile bursts, major burst at night (nocturnal) during slow-wave sleep
how is growth hormone transported and what is its half life
Transported with majority bound to growth-hormone binding protein to act as reservoir and to prolong half-life (protects against degradation)
Half-life is 6-20 minuteswhat
what does growth hormone stimulate
Stimulates insulin-like growth factor 1 (IGF-1) release from liver
what is growth hormones function
stimulation of postnatal longitudinal growth (anabolic and mitogenic effects)
production of growth hormone throughout life
Production increases after 1-2 years, peaks in puberty, begins to decline in adulthood and continues with aging
what is growth hormone secretion stimulated by
GHRH and ghrelin
GHRH (hypothalamus)
Hypoglycemia (promotes GHRH release)
Arginine
Catecholamines (also reduce GHIH/somatostatin) Dopamine
Cortisol, thyroid hormones and androgens also influence GH by modifying the responsiveness to GHRH and GHIH
Ghrelin (stomach, pancreas, kidney, liver, hypothalamus)
what is growth hormone inhibited by
somatostatin/GHIH and IGF1
Somatostatin / GHIH
Hyperglycemia
Increase in non-esterified fatty acids
Insulin-like growth factor 1 (IGF-1)
Directly inhibits somatotrophs
Stimulates GHIH (which further inhibits somatotrophs)
Somatostatin:
Synthesized by many parts of the brain and organs (pancreas, stomach, others)
Binds to (1) Galpha-i somatostatin receptor and promote tyrosine
phosphatase activity (2) K+ channels resulting in hyperpolarized cell (stops release of GH)
how does somatostatin/GHIH inhibit growth hormone?
binds g alpha somatostatin receptor and promote tyrosine phosphatase activity
or
k+ channels and hyper polarizes to stop release of growth hormone
growth hormone secretion decreases with age how?
n the adult, GH levels are reduced as a result of smaller pulse width and amplitude rather than a decrease in the number of pulses.
what type of receptor fro growth hormone
class 1 cytokine receptor family
Location: liver, bone, kidney, adipose tissue, muscle, brain, eye, heart and immune cells
There are 2 bindings sites which allow the GH receptors to dimerize once GH binds
Dimerization resulting in increased JAK activity which leads to phosphorylation of tyrosine residues
These will allow the release of activators of transcription proteins, which will promote the expression of GH- regulated genes (genes that are influenced by growth hormone)
what happens when growth hormone binds receptors
dimerization increasing JAK activity and phosphorylation tyrosine residues to release transcription proteins
growth hormone functions
longitudinal bone growth, lipolysis, protein synthesis, IGF1 production, reduce glucose uptake, gluconeogenesis, influences immune system, mood
what is IGF-1 regulated by
Regulated by GH, PTH and reproductive hormones (in bone)
IGF-1 function
stimulates bone
formation, protein synthesis,
glucose uptake into muscles,
neuronal survival, myelin
synthesis, bone turn over, collagen synthesis, linear growth, mitogen (DNA, RNA and protein synthesis)
IGF-1 throughout lifetime
Low at birth, increases during childhood/puberty, begins to decline in 3rd decade
outcomes of too much growth hormone
acromegaly (post puberty) or gigantism (pre puberty/ growth plate fusion)
what is acromegaly from
somatotorope adenoma
acromegaly cause
due to somatotrope adenoma resulting in over secretion of GH
bone and soft tissue impacts from acromegaly
Bone:
Acral bony overgrowth result in frontal bossing
Increased hand and foot size
Mandibular enlargement with prognathism
Wide space between incisor teeth
Soft tissue:
Increased heel pad thickness, increased shoe size, coarse facial features, large fleshy nose
neoplastic complications of acromegaly
increased cell proliferation
GH – increase JAK/STAT pathway–> proliferation BRCA1 – breast cancer
Suppression of regulatory proteins! they typically stop inappropriate DNA and cell replication–> colon and pituitary cancers
Mitogen
metabolic complications from acromegaly
Promote gluconeogenesis
Reduction in insulin signaling pathway
Insulin Resistance
neurologic complications of acromegaly
If the somatotrope adenoma (aka AP tumour) grows large enough, it can:
Impinge on the optic nerve (at the optic chiasm–> bitemporal hemianopsia)
Increase intracranial pressure (headaches, eventually impacting cortical function, selected cranial nerves)
neurologic complications of acromegaly
bitemporal hemianopsia
1/2 of outside eye cant see out of
acromegaly and cardiovascular impact
Cardiomyopathy with arrhythmia’s Left ventricular hypertrophy
Decreased diastolic function Hypertension
–>thickening of arteries bc of increased collagen synthesis
Upper airway obstruction with sleep apnea (common)
Central sleep dysfunction
Soft tissue laryngeal airway obstruction
–> increased connective tissue causing thickening of posterior tongue
Diabetes
gigantism cause
If increased GH secretion occurs before epiphyseal long bone closure (in children or adolescents) this results in gigantism
gigantism features
same as acromegaly plus increased height
prolactin is synthesized by? where?
lactotrophs
(15-20% of anterior pituitary);
what causes an increase in the amount of lactotrophs (to then make prolactin)
estrogen
amount of lactotrophs increases in response to estrogen (i.e. pregnancy)
when does secretion of prolactin increase
Secretion increases during sleep and reduces during wake hours
function of prolactin
development of mammary glands and milk production
how is prolactin inhibited
dopamine
Under tonic inhibition from the dopamine binding to D2 receptors on the lactotrophs; dopamine released from hypothalamus
Somatostatin and GABA also exert inhibitory impact
what is prolactin stimulated by
Stimulated by suckling and increased estrogen
Suckling results in reduction of dopamine release from hypothalamus
GnRH, serotonergic and opioidergic pathways also promote release as do Prolactin Releasing Factors (TRH, oxytocin, vasoactive intestinal peptide)
where is prolactin receptor
mammary gland, ovary, brain
prolactin function
- Developmammaryglands
- Milksynthesis
- Maintenanceofmilksynthesis
Milk synthesis is prevented during pregnancy by high progesterone levels
* - InhibitGnRH
What is the primary hormone responsible for stimulating both the synthesis and secretion of GH from somatotrophs?
A. Somatostatin
B. Insulin
C. Ghrelin
D. Growth hormone-releasing hormone (GHRH)
D. Growth hormone-releasing hormone (GHRH)
Which family of receptors do growth hormone cell surface receptors belong to?
A. G-protein couple receptors
B. Class 1 cytokine receptors
C. Tyrosine kinase receptors
D. Steroid receptors
B. Class 1 cytokine receptors
What is the primary physiologic effect of growth hormone?
A. Stimulation of brain function
B. Suppression of immune response
C. Promotion of adipocyte differentiation
D. Stimulation of postnatal longitudinal growth
D. Stimulation of postnatal longitudinal growth
What is the primary physiologic role of prolactin in the mammary gland?
A. Inhibition of mammary gland development
B. Suppression of milk synthesis
C. Stimulation of milk production
D. Regulation of lactose metabolism
C. Stimulation of milk production
