Today

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Today Oxy and VASO intro to the adrenal gland
hormones
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Antidiuretic Hormone (Vasopressin) 9 aa
peptide secreted from the posterior pituitary.
Within hypothalamic neurons, the hormone is
packaged in secretory vesicles with a carrier
protein called neurophysin, and both hormone and
carrier are released upon hormone secretion.

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Antidiuretic Hormone (Vasopressin) Roughly 60
of the mass of the body is water despite wide
variation in the amount of water taken in each
day, body water content remains incredibly
stable. Such precise control of body water and
solute concentrations is a function of several
hormones acting on both the kidneys and vascular
system, but there is no doubt that ADH is a key
player in this process.

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Effects on the Kidney single most important
effect of ADH is to conserve body water by
reducing urine output A diuretic is an agent
that increases the rate of urine formation.
Injection of small amounts of ADH into a person
or animal results in antidiuresis or decreased
formation of urine, and the hormone was named for
this effect.

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ADH hormone binds to receptors in the distal or
collecting tubules of the kidney and promotes
reabsorbtion of water back into the circulation.
In the absence of ADH, the kidney tubules are
virtually impermeable to water, and it flows out
as urine.

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ADH stimulates water reabsorbtion by
stimulating insertion of "water channels" or
aquaporins into the membranes of kidney tubules.
These channels transport solute-free water
through tubular cells and back into blood,
leading to a decrease in plasma osmolarity and an
increased osmolarity of urine.

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Effects on the Vascular System In many
species, high concentrations of ADH cause
widespread constriction of arterioles, which
leads to increased arterial pressure. It was for
this effect that the name vasopressin was coined.
In healthy humans, ADH has minimal pressor
effects.

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Control of ADH Secretion Most important variable
regulating ADH secretion is plasma osmolarity,
or the concentration of solutes in blood.
Osmolarity is sensed in the hypothalamus by
neurons known as an osmoreceptors, and those
neurons, in turn, simulate secretion from the
neurons that produce ADH

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Control of ADH Secretion When plasma osmolarity
is below a certain threshold, the osmoreceptors
are not activated and ADH secretion is
suppressed. When osmolarity increases above the
threshold, the ever-alert osmoreceptors recognize
this a the cue to stimulate the neurons that
secrete ADH. ADH concentrations rise steeply and
linearly with increasing plasma osmolarity.

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Osmotic control of ADH secretion makes perfect
sense. Imagine walking across a desert sun is
beating down and you begin to lose a considerable
amount of body water through sweating. Loss of
water results in concentration of blood solutes -
plasma osmolarity increases. Should you increase
urine production in such a situation? Clearly
not. Rather, ADH is secreted, allowing almost all
the water that would be lost in urine to be
reabsorbed and conserved. .

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There is an interesting parallel between ADH
secretion and thirst. Both appear to be
stimulated by hypothalamic osmoreceptors,
although probably not the same ones. The osmotic
threshold for ADH secretion is considerably lower
than for thirst, as if the hypothalamus is saying
"Let's not bother by invoking thirst unless the
situation is bad enough that ADH cannot handle it
alone."

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Secretion of ADH is also stimulated by decreases
in blood pressure and volume, conditions sensed
by stretch receptors in the heart and large
arteries. Changes in blood pressure and volume
are not nearly as sensitive a stimulator as
increased osmolarity, but are nonetheless potent
in severe conditions.

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For example, Loss of 15 or 20 of blood volume by
hemorrhage results in massive secretion of ADH
Another potent stimulus of ADH is nausea and
vomiting, both of which are controlled by regions
in the brain with links to the hypothalamus.

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Disease States Most common disease of man and
animals related to ADH is diabetes insipidus.
This condition can arise from either of two
situations Hypothalamic ("central") diabetes
insipidus results from a deficiency in secretion
of ADH from the posterior pituitary. Causes of
this disease include head trauma, and infections
or tumors involving the hypothalamus.

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Disease States Nephrogenic diabetes insipidus
occurs when the kidney is unable to respond to
ADH. Most commonly, this results from some type
of renal disease, but mutations in the ADH
receptor gene or in the gene encoding aquaporin-2
have also been demonstrated in affected humans.

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Disease States major sign of either type of
diabetes insipidus is excessive urine production.
Some human patients produce as much as 16 liters
of urine per day! If adequate water is available
for consumption, the disease is rarely
life-threatening, but withholding water can be
very dangerous. Hypothalamic diabetes insipidus
can be treated with exogenous ADH

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Biology of a Hangover ADH Inhibition When
alcohol is consumed, it enters the blood-causes
the pituitary gland to block the synthesis of
ADH. Hence, the kidneys send water directly to
the bladder instead of reabsorbing it into the
body. This is why drinkers have to make frequent
trips to the bathroom after urinating for the
first time after drinking.

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Biology of a Hangover ADH Inhibition According
to studies, drinking about 250 mls of an
alcoholic beverage causes the body to expel 800
to 1,000 mls of water This diuretic effect
decreases as the alcohol in the bloodstream
decreases, but the after effects help create a
hangover.

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Aquaporins Water Channels Water crosses cell
membranes by two routes -diffusion through the
lipid bilayer (NOT MUCH) -through water channels
called aquaporins. Functional characterization
of the first aquaporin was reported in 1992 Water
channels were suspected to exist well before that
time, because the osmotic permeability of some
types of cells was much too large to be accounted
for by simple diffusion across PM

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Aquaporins Water Channels The classical
aquaporins transport solute-free water across
cell membranes they appear to be exclusive water
channels and do not permeate membranes to ions or
other small molecules.

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The Aquaporin Family (6TMD) More than 10
different mammalian aquaporins have been
identified to date (likely more) . Closely
related water channel proteins have been isolated
from plants, insects and bacteria. Aquaporin-1
from human red blood cells was the first to be
discovered and is probably the best studied.

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Based on studies with aquaporin-1, it appears
that aquaporins exist in the plasma membrane as
homotetramers. Each aquaporin monomer contains
two hemi-pores, which fold together to form a
water channel.
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Patterns of Aquaporin Expression Each of the
aquaporins has an essentially unique pattern of
expression among tissues and during
development. summary of these attributes and some
of the important potential or known functions is
presented below Major Sites of Expression
Comments Aquaporin-0 Eye lens fiber cells
Fluid balance within lens Aquaporin-1 RBC
Osmotic protection Aquaporin-2 Kidney
collecting ducts Mediates ADH activity Aquaporin-3
Kidney (collecting ducts) Reabsorbtion of H2O
into blood Aquaporin-5 Salivary glands
Production of saliva
Lacrimal glands Production of tears
Aquaporin-7 Testis and spermAquaporin-8Testis,
pancreas, liver, othersAquaporin-9 Leukocytes
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Several interesting and important features of
aquaporin-mediated water transport are
illustrated in the principal cells that line
collecting ducts in the kidney. Water flowing
through these ducts can either continue on and be
voided in urine or be reabsorbed across the
epithelium and back into blood. Reabsorption is
essentially nil unless the epithelial cells see
ADH, which strongly stimulates reabsorption of
water. Collecting duct cells express at least
two aquaporins
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Aquaporin-2 is synthesized and present Yet, in
the absence of ADH hormone, resides in a pool of
membrane vesicles within the cytoplasm.Binding
of ADH to its receptor in the cell not only
stimulates transcription of the aquaporin-2 gene,
but causes the intracellular pool of aquaporin-2
to be inserted into the apical membrane. The cell
is now able to efficiently take up water from the
lumen of the duct. Aquaporin-3 is
constitutively expressed in the basolateral
membrane of the cell. When water floods into the
cell through aquaporin-2 channels, it can rapidly
exit the cell through the aquaporin-3 channels
and flow into blood.
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(AP2) Take up water from lumen, AP3 faciliate
its movement into the blood
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ADH bind receptor this activates a G protein and
Adenylate cyclase to increase cAMP which cause
Aquaporin 2 vesicles to fuse with the PM to move
water into the cells. Water comes in via A2 and
goes out into the blood via A3, hence preventing
loss via urine. Make sure you understand how ADH
results in water movement into the blood.

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Aquaporins and Disease Considering the
importance of water transport in a myriad of
physiologic processes, it is to be expected that
lesions in aquaporin genes or acquired
dysfunction in aquaporins may cause or contribute
to several disease states. The search for such
connections is still early, but 2 clear examples
of disease have been identified as resulting from
deficiency in aquaporins Mutations in the
aquaporin-2 gene cause hereditary nephrogenic
diabetes insipidus in humans. Mice homozygous
for inactivating mutations in the aquaporin-0
gene develop congenital cataracts.
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Oxytocin in a 9 aa peptide synthesized in
hypothalamic neurons and transported down axons
of the posterior pituitary for secretion into
blood.

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Oxytocin is also secreted within the brain and
from a few other tissues, including the ovaries
and testes. Oxytocin differs from ADH in 2 of
the 9 amino acids. Both hormones are packaged
into granules and secreted along with carrier
proteins called neurophysins.

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Physiologic Effects of Oxytocin In years past,
oxytocin had the reputation of being an
"uncomplicated" hormone, with only a few
well-defined activities related to birth and
lactation. As has been the case with so many
hormones, further research has demonstrated many
subtle but profound influences of this little
peptide. Nevertheless, it has been best studied
in females where it clearly mediates 3 major
effects

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Physiologic Effects of Oxytocin 3 major effects
Stimulation of milk ejection (milk letdown)
Milk is initially secreted into small sacs within
the mammary gland called alveoli, from which it
must be ejected for consumption or harvesting.
Mammary alveoli are surrounded by smooth muscle
(myoepithelial) cells which are a prominent
target cell for oxytocin. Oxytocin stimulates
contraction of myoepithelial cells, causing milk
to be ejected into the ducts and cisterns.

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Physiologic Effects of Oxytocin 3 major effects
Stimulation of uterine smooth muscle
contraction at birth At the end of gestation,
the uterus must contract vigorously and for a
prolonged period of time in order to deliver the
fetus. During the later stages of gestation,
there is an increase in abundance of oxytocin
receptors on uterine smooth muscle cells, which
is associated with increased "irritability" of
the uterus (and sometimes the mother as well).

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Physiologic Effects of Oxytocin 3 major effects
Stimulation of uterine smooth muscle
contraction at birth Oxytocin is released
during labor when the fetus stimulates the cervix
and vagina, and it enhances contraction of
uterine smooth muscle to facilitate parturition
or birth.

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Physiologic Effects of Oxytocin 3 major effects
Establishment of maternal behavior Successful
reproduction in mammals demands that mothers
become attached to and nourish their offspring
immediately after birth. It is also important
that non-lactating females do not manifest such
nurturing behavior. The same events that affect
the uterus and mammary gland at the time of birth
also affect the brain. During parturition, there
is an increase in concentration of oxytocin in
cerebrospinal fluid, and oxytocin acting within
the brain plays a major role in establishing
maternal behavior.

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• Physiologic Effects of Oxytocin
• 3 major effects
• Evidence for this role of oxytocin come from 2
  types of experiments.
• infusion of oxytocin into the ventricles of the
  brain of virgin rats or non-pregnant sheep
  rapidly induces maternal behavior.
• administration into the brain of antibodies that
  neutralize oxytocin or of oxytocin antagonists
  will prevent mother rats from accepting their
  pups.
• Other studies support the contention that this
  behavioral effect of oxytocin is broadly
  applicable among mammals.

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While there is no doubt that oxytocin stimulates
all of the effects described, doubt has recently
been cast on its necessity in parturition and
maternal behavior.

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Mice that are unable to secrete oxytocin due to
targeted disruptions of the oxytocin gene will
mate, deliver their pups without apparent
difficulty and display normal maternal behavior.
However, they do show deficits in milk ejection
and have subtle derangements in social behavior.
It may be best to view oxytocin as a major
facilitator of parturition and maternal behavior
rather than a necessary component of these
processes.

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Both sexes secrete oxytocin - what about its role
in males? Males synthesize oxytocin in the same
regions of the hypothalamus as in females, and
also within the testes and perhaps other
reproductive tissues. Pulses of oxytocin can be
detected during ejaculation. Current evidence
suggests that oxytocin is involved in
facilitating sperm transport within the male
reproductive system and perhaps also in the
female, due to its presence in seminal fluid. It
may also have effects on some aspects of male
sexual behavior.

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It may also have effects on some aspects of male
sexual behavior.
Intracerebroventricular (ICV) injection of
oxytocin (300 ng) produced an immediate cessation
in sexual behavior in sexually active male
prairie voles...

Other studies in guinea pigs show a role of OXY
in cohabitiation in males and females
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Control of Oxytocin Secretion The most important
stimulus for release of hypothalamic oxytocin is
initiated by physical stimulation of the nipples
or teats. The act of nursing or suckling is
relayed within a few milliseconds to the brain
via a spinal reflex arc. These signals impinge on
oxytocin-secreting neurons, leading to release of
oxytocin.

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A number of factors can inhibit oxytocin release,
among them acute stress. For example, oxytocin
neurons are repressed by catecholamines, which
are released from the adrenal glands in response
to many types of stress, including fright. So,
dont scare the cows in the milking parlor or set
off firecrackers around a mother nursing her
baby.

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Both the production of oxytocin and response to
oxytocin are modulated by circulating levels of
sex steroids. The burst of oxytocin released at
birth seems to be triggered in part by cervical
and vaginal stimulation by the fetus, but also
because of abruptly declining concentrations of
progesterone. Another well-studied effect of
steroid hormones is the marked increase in
synthesis of uterine oxytocin receptors late in
gestation, resulting from increasing
concentrations of circulating estrogen.

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Number of enzymes in a variety of tissues that
can degrade the neurohypophysial hormones in a
specific manner One example-oxytocinase-appears
in human blood in pregnancy, made in
placenta Kidney also has peptidases which break
down these hormones

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Hormone Other names Symbol(s) Target
Effect Oxytocin -
- Target Uterus, mammary glands
EffectUterine contractions
lactation Vasopressin Arginine vasopressin,
argipressin, antidiuretic hormone AVP, ADH
Target Kidneys or Arterioles
Effectstimulates water retention raises blood
pressure by contracting arterioles
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Lots of other neurohypophysial hormones
Hydrins -hydroosmotic peptides have role in
osmoregulatory adaptation in amphibians Urophysis-
gland in FISH Urotensins- teleost hormones. A
family of small peptides isolated from urophyses
of bony fishes. They have many different
physiological effects, including long-lasting
hypotensive activity and have been proposed as
antihypertensives. There are at least four
different compounds urotensin I, urotensin II,
urotensin III, and urotensin IV.
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Vasotocin (AVT) rather than vasopressin is
present in the pituitary of non mammal
vertebrates Important in sexual behavior and
muscle contraction Non-mammalian vertebrates
(fish, amphibians, reptiles and birds)

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POMC and the melanocortins ACTH made in pars
distalis in corticotrophs aMSH in pars
intermedia Both come from cleaved POMC aMSH and
ACTH have similar sequences within their
structure

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Adrenocorticotropic hormone, as its name implies,
stimulates the adrenal cortex. More
specifically, it stimulates secretion of
glucocorticoids such as cortisol, and has little
control over secretion of aldosterone, the other
major steroid hormone from the adrenal cortex.
Another name for ACTH is corticotropin.

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ACTH is secreted from the anterior pituitary in
response to corticotrophin-releasing hormone
(CRH) from the hypothalamus. CRH is secreted in
response to many types of stress, which makes
sense in view of the "stress management"
functions of glucocorticoids. CRH itself is
inhibited by glucocorticoids, making it part of a
classical negative feedback loop

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Within the pituitary gland, ACTH is produced in a
process that also generates several other
hormones. A large precursor protein named
proopiomelanocortin (POMC, "Big Mama") is
synthesized and proteolytically chopped into
several fragments. Not all of the cleavages
occur in all species and some occur only in the
intermediate lobe of the pituitary.

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The major attributes of the hormones other than
ACTH that are produced in this process are
summarized as follows Lipotropin Originally
described as having weak lipolytic effects, its
major importance is as the precursor to
beta-endorphin.Beta-endorphin and
Met-enkephalin Opioid peptides with
pain-alleviation and euphoric effects.Melanocyte
-stimulating hormone (MSH) Known to control
melanin pigmentation in the skin of most
vertebrates.

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ACTH acts on steriodogenic tissue of the
adrenal glands secrete a number of steriod
hormones that profoundly effect carbohydrate and
mineral metabolism. Steroid tissue surrounds
the adrenal medulla to form the adrenal
cortex.

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The Adrenal Gland When you think about the
adrenal glands, you should think about stress.
Stress can take many forms taking an
examination, recovering from a broken bone,
running away from an invading army, or
maintaining proper levels of energy substrates in
the face of even mild starvation. For human
males, there is even considerable stress
associated with shopping.

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The adrenal produces 3 major classes of hormones,
each of which aid in dealing with the multitude
of small and large stresses faced by animals and
people almost daily. There is no doubt that at
least 2 of these groups - glucocorticoids and
mineralocorticoids - are necessary for life.

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The adrenal cortex is a factory for steroid
hormones. In total, at least 2-3 dozen different
steroids are synthesized and secreted from this
tissue, but two classes are of particular
importance Class of Steroid Major
Representative Physiologic Effects Mineraloco
rticoids Aldosterone Na, K and water
homeostasis Glucocorticoids Cortisol
Glucose homeostasis and many
others Additionally, the adrenal cortex
produces some sex steroids, particularly
androgens.