Anti-Diuretic Hormone (ADH), aka Vasopressin

ADH, or vasopressin, is an important hormone involved in the conservation of water.

 

Function

ADH is an important mediator of fluid homeostasis, working on the kidney to increase water and sodium reabsorption, both acting to increase blood volume. ADH regulates water permeability in the late distal tubule and collecting duct, primarily through expression of aquaporin-2.

 

ADH and the Kidney

Normally, there is some basal level of ADH secreted. In the absence of ADH, the kidney produces 18L of very dilute urine (50 mOsm/kg H20).

Some fluid can be absorbed by the cortical collecting duct, but ADH increases this amount dramatically.

ADH binds to the V2 Receptor, a GPCR, and activates adenylyl cyclase, cAMP, and PKA, which inserts AQP2 into the apical membrane. ADH also induces transcription of AQP2.

Basolateral membranes of principal cells constitutively express AQP3 and AQP4. Insertion of AQP2 promotes water absorption and raises the osmolality of urine.

ADH causes tubutar osmolarity to equilibriate with cortical interstitial osmolarity (~290 mOsm). As the fluid passes through the medulla, equilibriation can increase urine osmolality to a maximum of 1200 mOsm/kg H2O.

ADH also increases sodium reabsorption in the principal cells of the CCT.

 

 

Regulation of Expression

 

ADH secretion can result from a number of causes and in response to a variety of stimuli, including:

 

ADH is controlled by volume and osmolarity status. Hypothalamic osmoreceptors signal osmolarity, while baroreceptors signal volume change. Osmoreceptors are more sensitive in inducing ADH secretion.

 

Volume changes both the set point and the slope of ADH secretion, which is normally at 280 mOsm.

The sensitivity of osmoreceptor-mediated ADH secretion is increased during hypoervolemia.

 

 

ADH is released from neurons of the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus. Neuron endings are in the posterior pituitary, with ADH released directly into the venous circulation following proteolytic cleavage. Active ADH is 9 aa long.

 

 

 

Consequences of Overexpression

 

Non-regulated pituitary or ectopic release of ADH (Syndrome of Inappropriate ADH Release, SIADH) causes abnormally concentrated urine.

 

Consequences of Underexpression

 

Lack of ADH production or release causes central diabetes insipidus.

Lack of ADH resonse in the kidney causes nephrogenic diabetes insipidus.

 

Signalling Pathways

 

 

Structure