Changes in AVP secretion are primarily regulated by even minor changes in the osmolality of body fluids (as little as 1% can suffice). Osmoreceptors, which are distinct from the cells responsible for AVP synthesis and secretion, are situated in the organum vasculosum of the lamina terminalis (OVLT) in the hypothalamus and are responsible for monitoring changes in body fluid osmolality. These osmoreceptors detect changes in osmolality by either shrinking or swelling. Recent research indicates that transient receptor potential vanilloid (TRVP) cation channels play a role in the response of osmoreceptor cells to changes in body fluid osmolality. However, osmoreceptors only respond to solutes in plasma that act as effective osmoles. For instance, urea is an ineffective osmole when considering the function of osmoreceptors, so an increase in plasma urea concentration alone has little impact on AVP secretion. 
When the effective osmolality of plasma increases, osmoreceptors send signals to the AVP synthesizing/secreting cells found in the supraoptic and paraventricular nuclei of the hypothalamus, thereby stimulating AVP synthesis and secretion. Conversely, angiotensin II also stimulates AVP secretion, with the cells that mediate this response located in the subfornical organ (SFO). 
The AVP gene is located on chromosome 20 and comprises three exons, two introns, and approximately 2000 base pairs. This gene encodes a preprohormone that includes a signal polypeptide, the AVP molecule, neurophysin, and a glycopeptide (copeptin). In the rough endoplasmic reticulum, the signal peptide is cleaved off as the cell processes the preprohormone. Once packaged in neurosecretory granules, the preprohormone is further cleaved into AVP, neurophysin, and copeptin molecules. These neurosecretory granules are then transported to the posterior pituitary through the axon and stored in the nerve endings until they are released. When the neurons are stimulated to secrete AVP, the action potential opens Ca++ channels in the nerve terminal, leading to an increase in intracellular [Ca++] and subsequent exocytosis of the neurosecretory granules. All three peptides are secreted during this process, although neurophysin and copeptin do not have a known physiological function. 
Inhibition of secretion occurs when the osmolality of plasma is reduced. Since AVP is rapidly degraded in the plasma, circulating levels can drop to zero within minutes after secretion is inhibited. Consequently, the AVP system can quickly respond to fluctuations in body fluid osmolality. 
Fig. 35.4A illustrates the impact of changes in plasma osmolality on circulating AVP levels, showing a steep slope that accounts for the sensitivity of this system. The plasma osmolality value at which AVP secretion begins to increase is referred to as the set point of the system. Below this set point, there is virtually no release of AVP. The set point varies among individuals and is determined by genetics, ranging from 275 to 290 mOsm/kg H2O in healthy adults (average ≈ 280–285 mOsm/kg H2O). Various physiological factors can also alter the set point in a given individual, such as changes in blood volume and pressure. Additionally, pregnancy is associated with a decrease in the set point, although the mechanism behind this shift is not completely understood, it is likely related to elevated hormone levels during pregnancy, such as relaxin and chorionic gonadotropin. 
The secretion of AVP can also be influenced by nonosmotic factors, specifically hemodynamic factors.
Changes in the osmolality of body fluids (changes as minor as 1% are sufficient) play the most important role in regulating AVP secretion. The receptors that monitor changes in osmolality of body fluids (termed osmoreceptors) are distinct from the cells that synthesize and secrete AVP, and are located in the organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus.
The osmoreceptors sense changes in body fluid osmolality by either shrinking or swelling. Recent studies have provided evidence that transient receptor potential vanilloid (TRVP) cation channels are involved in the response of the cells to changes in body fluid osmolality. The osmoreceptors respond only to solutes in plasma that are effective osmoles (see ). For example, urea is an ineffective osmole when the function of osmoreceptors is considered. Thus elevation of the plasma urea concentration alone has little effect on AVP secretion.
When the effective osmolality of the plasma increases, the osmoreceptors send signals to the AVP synthesizing/ secreting cells located in the supraoptic and paraventricular nuclei of the hypothalamus, and AVP synthesis and secretion are stimulated. Conversely, when the effective cAngiotensin II also stimulates AVP secretion; the cells that mediate this response are located in the subfornical organ (SFO).
The gene for AVP is found on chromosome 20. It contains approximately 2000 base pairs with three exons and two introns. The gene codes for a preprohormone that consists of a signal polypeptide, the AVP molecule, neurophysin, and a glycopeptide (copeptin). As the cell processes the preprohormone the signal peptide is cleaved off in the rough endoplasmic reticulum. Once packaged in neurosecretory granules, the preprohormone is further cleaved into AVP, neurophysin, and copeptin molecules. The neurosecretory granules are then transported down the axon to the posterior pituitary and stored in the nerve endings until released. When the neurons are stimulated to secrete AVP, the action potential opens Ca++ channels in the nerve terminal, which raises the intracellular [Ca++] and causes exocytosis of the neurosecretory granules. All three peptides are secreted in this process. Neurophysin and copeptin do not have an identified physiological function.
osmolality of the plasma is reduced, secretion is inhibited. Because AVP is rapidly degraded in the plasma, circulating levels can be reduced to zero within minutes after secretion is inhibited. As a result the AVP system can respond rapidly to fluctuations in body fluid osmolality.
Fig. 35.4A illustrates the effect of changes in plasma osmolality on circulating AVP levels. The slope of the relationship is quite steep and accounts for the sensitivity of this system. The set point of the system is the plasma osmolality value at which AVP secretion begins to increase. Below this set point, virtually no AVP is released. The set point varies
CHAPTER 35 Control of Body Fluid Osmolality and Volume among individuals and is genetically determined. In healthy adults it varies from 275 to 290 mOsm/kg H2O (average ≈ 280–285 mOsm/kg H2O). Several physiological factors can also change the set point in a given individual. As discussed later, alterations in blood volume and pressure can shift it. In addition, pregnancy is associated with a decrease in the set point. The mechanism responsible for the set-point shift with pregnancy is not completely understood but is likely due to hormone levels (e.g., relaxin and chorionic gonadotropin) that are elevated during pregnancy.
Hemodynamic (Nonosmotic) Control of AVP Secretion