Oxytocin and vasopressin are peptide hormones produced in the hypothalamus and released from the posterior pituitary gland. Oxytocin regulates milk release and uterine contractions during labor, while vasopressin regulates water balance. Both hormones have similar structures but different physiological roles. Oxytocin is involved in romantic attachment, sexual response, social behaviors, and wound healing by reducing anxiety and inflammation. Vasopressin regulates water reabsorption in the kidneys to maintain fluid homeostasis and also mediates blood pressure responses. Diseases related to these hormones include diabetes insipidus and syndrome of inappropriate vasopressin secretion.

1. NEUROHYPOPHYSIAL HORMONES
OXYTOCIN
STRUCTURE:
Oxytocin has the chemical formula C43H66N12O12S2.Oxytocin is a peptide hormone.Itis a
relatively short polypeptide,being composed of only nine amino acids (a nonapeptide).The
sequence is cysteine - tyrosine -isoleucine - glutamine - asparagine - cysteine - proline -
leucine - glycine (CYIQNCPLG).The cysteine residues form a sulfur bridge.Oxytocin has a
molecular mass of 1007 daltons. One international unit (IU) of oxytocin is the equivalent of
about two micrograms of pure peptide.
Vasopressin: The structure of oxytocin is very similar to that of vasopressin, an antidiuretic hormone that
is also a nonapeptide: cysteine - tyrosine - phenylalanine - glutamine - asparagine - cysteine - proline -
arginine - glycine).These neurohypophysial hormones are closely related structurally but they serve quite
different physiological roles.Oxytocin controls milk release from the mammary gland and contraction of the
uterus,whereas AVP is concerned with water balance. Vassopressin, whose residues also form a sulfur
bridge, has a sequence that differs from oxytocin by two amino acids,a Phenylalanine and an Arginine at the
3 and 8 position.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to
act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone
(CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are
adjacent to magnocellular neurons that make vasopressin, and are similar in many respects.

2. Oxytocin was the first hormone for which the structure was identified and which was synthesized in the
laboratory (Blakemore and Jennett 2001). Oxytocin and vasopressin were isolated and synthesized by
Vincent du Vigneaud in 1953, work for which he received the Nobel Prize in Chemistry in 1955.
PHYSIOLOGICAL ROLE: Oxytocin is involved in the control of milk release and in uterine
contraction during labor.Vasopressin, or antidiuretic hormoneas its name implies,is importantin the
homeostatic control of the extracellular fluid volume.the antidiuretic responseis of survival valueto
individuals of both sexes.OT,on the other hand,apparently functions only during specific times in the
reproductivecycle of the adult female.
Oxytocin controlsmilk release and uterine contractions: Oxytocin is a hormonethat
plays only a transitory role,possibly specific to the female,andthen,in somecases,only if she becomes
pregnantand delivers a child at term.
Milk release(let down):OTfunctions in the control of milk release after parturition.Sensory
nerve endings,which arelocalized to the areolae and nipples of the breast,arestimulated by suckling
and afferent neuralpathways conductthese stimuli to the neurohypophysis.
At parturition,dilation of the cervix(vaginalstretching) may also be a stimulus to OTsecretion.
There is increased uterine activity during mating, and milk ejection during coitus in the human female
and other animals has been reported.
The major target organ of OTis the mammary gland of the pregnanatfemale.
Uterine contraction: OT has been used for years to induce labor in human females as it contacts
the myometrium(uterotropic action).Although OTin the maternal circulation throughout
pregnanacy,OTconcentration in the blood increase only during the final stages of
labor,notbefore.Circulating OTis not essential for the initiation or maintenanceof spontaneous
labor.parturation can begin in the absence of circulating OTand although OT antiserumsuppresses
lactation,it fails to affect parturition.
Vascularsmooth muscle actions:Neurohypophysialhormones contractor relax vascular
smooth muscle.There may be two different kinds of neurohypophysialhormonereceptors,onethat
subserves contraction and other that subserves relaxation. OTis highly effective in contracting human
umbilical arteries and veins whereas AVP is relatively inactive.
Romantic attachment:In somestudies, high levels of plasma oxytocin have been correlated
with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can
increase due to the lack of physicalaffection. Oxytocin may aid romantically attached couples by
decreasing their feelings of anxiety when they are separated.

3. Human sexual response:Plasma OTlevels increaseduring sexual arousal(self-stimulation) in
both women and men and are significantly higher during orgasm/ejacuation than during prior
baseline testing.OT is secreted specifically at the time of ejacuation in males.This is preceded by a rise
in AVP secretion during arousal,which returns to baseline values by the time of ejacuation.AVP release
during arousalmay be associated with specific suppression of OTuntil ejacuation.OTmay play a role
in the physiology of sexual responses by facilitating contractions of the smooth muscles of the uterus
and vagina in women.Likewise,releaseof OTduring sexual responses in men may be related to
increased contractility of reproductivesmooth muscletissue.Thus, OTmay enhanceboth spermand
egg transport,thereby promoting reproductivesuccess.
Social Behaviourand wound healing: Oxytocin is also thought to modulate inflammation by
decreasing certain cytokines. Thus, the increased release in oxytocin following positive social
interactions has the potential to improvewound healing. A study by Marazzitiand colleagues used
heterosexual couples to investigate this possibility. They found increases in plasma oxytocin following
a social interaction were correlated with faster wound healing. They hypothesized this was due to
oxytocin reducing inflammation, thus allowing the wound to heal morequickly. This study provides
preliminary evidence that positive social interactions may directly influence aspects of health.
Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security
when in the company of the mate. This suggests oxytocin may be important for the inhibition of the
brain regions associated with behavioralcontrol, fear, and anxiety, thus allowing orgasmto occur.
Research has also demonstrated that oxytocin can decreaseanxiety and protect against stress,
particularly in combination with social support.
Vasopressin(AVP) mediates osmoregulationand blood pressure
responses:Arginine Vasopressin(AVP) has two major physiologicalactions:Itinduces the
contraction or relaxation of certain types of smooth muscle and it promotes the movement of water
and Na+
across epithelial tissues,notably thedistal tubule of the mammalian kidney and the skin and
urinary bladder of amphibians.
Effects on the Kidney:The single most importanteffect of antidiuretic hormoneis to conserve
body water by reducing the loss of water in urine. A diuretic is an agent that increases the rate of
urine formation. Injection of small amounts of antidiuretic hormoneinto a person or animal results in
antidiuresis or decreased formation of urine, and the hormonewas named for this effect.
Antidiuretic hormonebinds to receptors on cells in the collecting ducts of the kidney and promotes
reabsorption of water back into the circulation. In the absenseof antidiuretic hormone, the collecting
ducts are virtually impermiable to water, and it flows out as urine.
Antidiuretic hormonestimulates water reabsorbtion by stimulating insertion of "water channels"
or aquaporins into the membranes of kidney tubules. These channels transportsolute-freewater

4. through tubular cells and back into blood, leading to a decrease in plasma osmolarity and an increase
osmolarity of urine.
Osmoregulation and control of antidiuretic hormone secretion:The mostimportant
variable regulating antidiuretic hormone 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, stimulate secretion fromthe neurons that produceantidiuretic hormone.
When plasma osmolarity is below a certain threshold, the osmoreceptors arenot activated and
secretion of antidiuretic hormoneis suppressed. When osmolarity increases abovethe threshold, the
ever-alert osmoreceptors recognizethis as their cue to stimulate the neurons that secreteantidiuretic
hormone. As seen the the figure below, antidiuretic hormoneconcentrations rise steeply and linearly
with increasing plasma osmolarity.
Osmotic control of antidiuretic hormonesecretion makes perfect sense. Imaginewalking across a
desert: the 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, antidiuretic hormoneis secreted,
allowing almost all the water that would be lost in urine to be reabsorbed and conserved.
There is an interesting parallel between antidiuretic hormonesecretion and thirst. Both phenomena
appear to be stimulated by hypothalamic osmoreceptors, although probably notthe same ones. The
osmotic threshold for antidiuretic hormonesecretion is considerably lower than for thirst, as if the
hypothalamus is saying "Let's not bother him by invoking thirst unless the situation is bad enough that
antidiuretic hormonecannot handle it alone."
Secretion of antidiuretic hormone is also stimulated by decreases in blood pressureand volume,
conditions sensed by stretch receptors in the heart and large arteries. Changes in blood pressureand
volume are not nearly as sensitive a stimulator as increased osmolarity, but are nonetheless potent in
severeconditions. For example, Loss of 15 or 20% of blood volume by hemorrhageresults in massive
secretion of antidiuretic hormone.
Another potent stimulus of antidiuretic hormoneis nausea and vomiting, both of which arecontrolled
by regions in the brain with links to the hypothalamus.
Mechanism of action:
Oxytocin
i)A rise in Ca2+
,produced either spontaneouslyor by an agonist such as OT interacting with its
receptor(R),causes Ca2+
to bind to calmodulin(Ca2+
/CaM).
ii)This activates myosine light chain kinase(MLCK).This kinase then phosphorylates light
chains on myosine(P-myosine).This allows actin binding and activates myosine Mg-
ATPase,thus contraction can occur with hydrolysis of ATP.

5. P-myosine is dephosphorylated by phosphatases,leading to relaxation.
iii)If MLCK is phosphorylated,forexample by Ca2+
calmodulin-dependentprotein kinase II,then
it is much less efficientat phophorylating myosine,and force falls.Reductionof Ca2+
will also
promote relaxation.
Vasopressin.
Vasopressinacts on three differentreceptors,vasopressinreceptorV1a (which initiates
vasoconstriction,liver gluconeogenesis,platelet aggregation and release of factor VIII),
vasopressinreceptorV1b (which mediates corticotrophinsecretionfrom the pituitary) and
vasopressinreceptorV2 which controls free water reabsorptionin the renal medullar. The
binding of vasopressinto the V2 receptoractivates adenylate cyclase which causes the
release of aquaporin 2 channels into the cells lining the renal medullar duct. This allows water
to be reabsorbeddown an osmotic gradient so the urine is more concentrated.

6. Pathophysiology:
Diabetes Insipidus: The mostcommon diseaseof man and animals related to antidiuretic
hormoneis diabetes insipidus. This condition can arise fromeither of two situations:
 Hypothalamic ("central") diabetesinsipidus results froma deficiency in secretion of antidiuretic
hormonefromthe posterior pituitary. Causes of this diseaseinclude head trauma, and
infections or tumors involving the hypothalamus.
 Nephrogenic diabetesinsipidus occurs when the kidney is unable to respond to antidiuretic
hormone. Most commonly, this results from sometype of renal disease, but mutations in the
ADH receptor gene or in the gene encoding aquaporin-2 havealso been demonstrated in
affected humans.
The major sign of either type of diabetes insipidus is excessiveurine production. Some human patients
produceas much as 16 liters of urine per day!If adequate water is available for consumption, the
diseaseis rarely life-threatening, but withholding water can be very dangerous. Hypothalamic
diabetes insipidus can be treated with exogenous antidiuretic hormone.
Syndrome of inappropriate vasopressin secretion: The state of continual AVP release
without relationship to plasma osmolarity or volume is referred to as the syndromeof inappropriate
vasopressin secretion.

7. The syndromeis chatracterized by an inability to excrete a maximally dilute urine,which results in
retention of water,an expansion of extracellular fluid volume,and a resultantdilutional hyponatremia.
The most common cause of excessiveAVP secretion is malignancy;AVP is secreted froma small cell
carcinoma of the lung.Although plasma and urinary levels of AVP may be markedly elevated,the
amount of hormonein the blood or urine may be similar to that of normal individuals.