lect 1-3 Flashcards
what is endocrine chemical communication?
secretory cells secrete in blood stream and travels to distant target cells
what are features of endocrine glands. name some glands
ductless. fenestrated capillaries.
pituitary, thyroid, adrenal glands
what is neuroendocrine chemical communication?
neurosecretory nerve cells release neurohormones into the general circulation or in the hypothalamus-hypophyseal portal circulation
what are features of neuroendocrine communication?
reaches a large number of target cells;
indirect, relatively slow communication
what is the hypothalamus-hypophyseal portal circulation
blood stream from hypothalamus to anterior pituitary gland
describe the parvocellular system
small cells system: synthesis of hypophysiotropic hormones. released in ME
describe the magnocellular system
big cells system: produces neurohypophyseal peptides (ex OT and vasopressin)
name the 5 hypothalamic releasing factors
CRH corticotropin releasing hormone
GHRH growth hormone releasing hormone
GnRH gonadotropin releasing hormone
Somatostatin
TRH thyrotropin releasing hormone
what are the 2 neurohypophyseal peptides
oxytocin, vasopressin
what is POMC?
pro-opiomelanocortin, a prohormone precursor protein that gets processed in a tissue-specific manner to yield biologically active peptides
what is the endocrine master switch of the neuroendocrine system
pituitary gland
4 ways to control hypothalamic hormone release
- indirect stimulation/inhibition of neurosecretory cell via interneurons
- direct innervation via axo-dendritic / axo-somatic synapses
- pre-synaptic inhibition via axo-axonis synapses
- direct release of hypothalamic dopamine in portal blood stream
what is the most common neuroendocrine messenger?
peptides
when we say “central”, what do we mean?
hypothalamic
what takes longer, secretion or production of neuropeptides?
production
what happens in large dense-core vesicles?
processing, storage, and degradation of peptides.
cleaving out of bioactive peptide sequence.
what happens in rough ER for peptides production?
production of a large precursor proteins
where does the large precursor protein go to mature?
Golgi apparatus / TGN (actually LDCVs?)
what is always cleaaved off when it gets to the ER lumen ?
n-terminal signal peptide that signals to go to the ER
what is prohormone convertase?
enzyme that converts complex precursor proteins into active biological component
which prohormone convertase are present in neurons and endocrine cells?
PC1/PC3, PC2
what is special about pro-opiomelanocortin?
It can be cleaved at 7 different cleavage sites to give many different hormones:
ACTH, CLIP, JP, LPH, MSH, PC, beta-endorphin
what is precursor protein cleavage dependent on?
the location (ex hypothalamus, pituitary) of the endocrine cells or neurons, and mostly pH and PC expression
how is the pH in secretory granules?
acidic
what is ACTH and its role?
adrenocorticotropic hormone: reduces stress response by increase cortisol release by adrenals, which decrease CRH levels through neg feedback
what is found in LDCV’s membrane to help with post precursor protein processing?
prohormone convertases and proton pump that pumps protons in vesicles (more protons = low pH)
what happens to vesicles in the TNG?
get reduced
what are thinner axons or dendrites?
axons
what is white and gray matter?
white is myelinated axons
gray to nerve cell bodies; where neuronal processing happens
what defines cortex?
ordered structure of neurons cell bodies (has layers/laminae)
what defines nuclei?
neurons with similar topography and/or cellular morphology, connectivity, and neurochemical characteristics (expression of the same transmitters, peptides, etc.)
embryologically, what do the neural tube and neural crest become?
neural tube = CNS
neural crest = PNS
what makes the walls of the 3rd ventricle?
hypothalamus
what structure is the hypothalamus not directly linked to?
neocortex
what are the hypothalamus humoral inputs and outputs?
humoral inputs: steroids, peptide hormones at MBH, cytokines, neuropeptides
outputs: to the pituitary
what are hypothalamus neural inputs and outputs?
neural inputs: amygdala, limbic structures, lower brain stem, spinal cord, hippocampus, septum, thalamus
neural outputs: limbic structures, thalamus, brainstem
what are the hypothalamic main regions rostral to caudal?
preoptic – anterior – tuberal – mammillary
what structure is considered part of the periventricular hypothalamic zone even if it is not located in it? what system is it part of?
supraoptic nucleus SO
magnocellular system
what nucleus dominates the preoptic hypothalamic region?
medial preoptic nucleus (in medial zone)
what does the suprachiasmatic nucleus do?
biological master clock. gets direct input from retina
what is the difference between supraoptic and paraventricular neurons?
supraoptic has only magnocellular neurons, PVN has parvo and magno
how is the pituitary connected to the brain?
via median eminence and infundibulum
what happens if a pituitary tumor develops?
compressed hypothalamus
what are the pituitary hormones?
ACTH, beta-endorphin, alphaMSH, GH, prolactin, FSH, LH, TSH
what factor stimulates GH?
insulin-like Growth Factor-1 IGF-1
what does TSH do?
thyrotropin stimulates T3 and T4 secretion from thyroid gland
what does FSH do?
- stimulate primary follicle growth
- stimulate estrogen secretion in females
- stimulate sperm production
- stimulate inhibin secretion in males
what does LH do?
- stimulate ovulation
- stimulate corpus luteum formation
- stimulates progesterone secretion in females
- stimulates androgen secretion from leydig cells in males
what does prolactin do?
- initiates milk production and secretion
- stimulates the gonads
what are pituitary’s 2 embryological sources?
adenohypophysis (anterior pit) that arises from Rathke’s pouch in the roof of the developing pharynx.
neurohypophysis (post pituitary) originates from diencephalon base (neuroectoderm) and contain ME and infundibulum.
which anterior pituitary cells are basophilic? (stain blue) what do they secrete?
gonadotropes (FSH, LH), thyrotrope (TSH)
which anterior pituitary cells are chromophobic?
corticotropes (ACTH)
which anterior pituitary cells are acidophilic? (stain orange)
somatotropes (GH)
lactotrope (PRL)
GH acts on which structures?
liver (produce IGF) and bones
what hormones are secreted by intermediate pituitary lobe?
melanocyte stimulating hormone (MSH), beta-endorphin
what is beta-endorphin’s effect?
neuromodulator, circulating analgesic
in which pituitary love does the intermediate lobe infiltrate?
in the posterior lobe
what is the pituitary posterior (neural) lobe made of?
terminations of neurosecretory axons from the hypothalamo-hypophyseal tract and fenestrated capillaries into which the neurohormones are released (NO CELL BODIES ONLY GLIAL CELLS)
what hormones are secreted by posterior pituitary?
OT and VP (ADH)
what are herring bodies and where are they found?
swelling of axons / terminals full of neurohormone filled secretory granules in posterior pituitary
what technique can herring bodies be stained with?
gomori technique (appear super dark)
what are pituicytes? where can they be found?
specialized glial cells in posterior pituitary (only cells in post pit).
support neurosecretory axons
appear super pale
where does the ME release hormones?
in hypophyseal portal veins that go to anterior pituitary and supply blood
what is the definition of a hypophysiotropic hormone?
releasing and release-inhibiting hormone present in ME, whose concentration is higher in hypophyseal portal system than in general circulation and correlated with rate of release of a particular hypophyseal hormone
another name for pituitary
hypophysis
where is CRH found and what does it do?
PVN, PVa, Arc parvocellular neurons; stimulates ACTH. cam synthesize enkephalin, cholecystokinin CCK, neurotensin NT, VP, angiotensinII
where is TRH found?
PVN, PVa, ARC
where is GnRH found?
preoptic area, Arc. more restricted distribution
where is GHRH found?
Arc
where is somatostatin found?
POA, PVa, PVN, Arc. widespread distribution even outside hypothalamus. It is THE inhibitory hormone in pituitary.
where is dopamine found?
Arc.
it acts on MSH release
where are neurons that project to ME located?
anterior portion of periventricular zone around 3rd ventricle
name arteries/veins of the hypophysial blood supply?
superior hypophyseal artery: outer zone of the median eminence. recievese hypothalamic hormones, give rise to:
hypophyseal portal veins: carry hypophysiotropic hormones in the anterior pituitary
inferior hypophyseal artery: blood supply to posterior pituitary
sup, lat, inf hypophyseal veins: drain blood from all pituitary in cavernous sinus
where is ME located? what is a characteristic?
mediobasal hypothalamus MBH.
open blood-brain barrier (fenestrated capillaries): circumventricular organ
what do circumventricular organ lack of blood-brain barrier do?
allows free diffusion of macromolecules between plasma and interstitial fluid
what characterized the 2 layers of ME?
internal layer is not open. it is where axons from magnocellular neurons are
external layer is open: site of secretion. has parvocellular neurons
how can parvo vs magnocellular neurons be identified in the lab?
parvo carry CRH
magno carry OT and VP
what are the 3 ways to feedback control of hypothalamic hormone release?
long: from organ through hormones or sensory neuronal input
short: through pituitary hormones acting directly on hypothalamus
ultrashort: auto or paracrine action of hypothalamic hormone within one nucleus or through intra-hypothalamic projections
many neuropeptides require what toxin to be visualized in cell bodies>
colchicine (depolarizes microtubules to inhibit axonal transport)
what does adrenalectomy cause?
CRH accumulation and overproduction due to removal of target feedback from adrenal cortex
what and where do magnocellular neurons mainly secrete?
OT and AVP from PVN and SON neurons to terminals and varicosities in posterior pituitary
what is called the “intermediate” between AVP and OT?
vasotocin (isoleucin at pos 3 like OT, arg at pos 8 like VP)
what caused higher vertebrate to have both VP and OT?
gene duplication event early in vertebrate evolution
hat are AVP and OT always found and released with?
neurophysins: byproduct of the maturation cleavage (neurophysin I with OT, II with AVP).
stainable material in herring bodies
why do we think OT and AVP were formed by gene duplication and inversion?
both genes sit in inverse order with inverted reading frame orientation
in what exon is OT and AVP’s hormone sequence contained
exon 1
what does the OT and AVP precursor protein contain?
signal peptide, the hormone sequence
proper, a consensus sequence (gly-lys-arg) for proteolytic maturation, and neurophysin
what kind of receptors do OT and AVP bind to?
G-protein-coupled receptors
what are the AVP receptors?
V1A, V1B, V2
how do OT and AVP work biologically?
OTR, V1A, V1B are coupled to phospholipase C -> inositol triphophate and 1-2diacylglycerol -> Ca2+ release -> activate protein kinase C.
V2 is coupled to adenylate cyclase -> increase in cAMP
describe OTR
g- protein-coupled receptor with 7 TM domains, extracellular N terminus
all SON projection neurons are what type? where do they project
magnocellular; all express OT or AVP; project to posterior pituitary
describe the distribution of OT vs AVP neurons in the PVN
OT neurons: rostral, less
AVP neurons: caudal and lateral, more numerous
which is more homogenous between the SON and the PVN?
SON is more homogenous
in rats, what portion of magnocellular neurons are accessories?
1/3
what signal do OT neurons get to stimulate uterine contractions?
norepinephrine neurons that get mechanosensory info
where do OT neurons get info from to send antidiuretic signal
baroreceptors and paraventricular organs, CCK, send info to NSTm VLM
is OT and antidiuretic hormone?
NO ONLY AVP IS
what is the main stimuli for vasopressin release?
plasma osmolality
where are central osmoreceptors located?
3rd ventricle anterior wall, in subfornical organ SFO and OVLT
what cranial nerves carry info from peripheral baro and osmoreceptors?
IX and Xth
all this osmolarity input goes where?
mainly to PVN
what is AVP’s main action?
promoting water reabsorption in collecting tubules by stimulating aquaporins insertion
volume or pressure drops, what does it do to vasopressin?
increase plasma angiotensin II, activates baroreceptors -> increases vasopressin concentration in plasma. it increases vasoconstriction
what receptors do AVP neurons get hypovolemia signal?
stretch and baroreceptors in the aortic arch
what is angiotensin precursor?
angiotensinogen (cleaved by renin pro-hormone convertase)
what is angiotensinogen effect?
increase aldosterone, increase NE = increase VP release = increase renal water retention
AVP is colocated in magnocelullar neurons with what hormone?
Apelin
are apelin and AVP in the same vesicles?
no
where is apelin expressed (w avp)
SON and PVN neurons and in ME
what are apelin’s diuretic effect?
reduces plasma AVP and increases diuresis (opposit of water reabsorption!)
what happened to water deprived rats apelin and AVP levels?
increase in apelin AND AVP neurons activity
what is the increase in apelin in neurons of water deprived rats due to?
increased accumulation of apelin due to decreased secretion, inhibited by AVP (V1 R activation)
what happens to magnocellular cells plasticity during lactation and dehydration?
withdrawal of astrocytic processes to allow for direct apposition of somatic and dendritic membranes
