Synthesis, Transport, and Secretion
Antidiuretic hormone is produced as a prohormone in the supraoptic and paraventricular neurons of the hypothalamus.
Following synthesis, the hormone is not released directly into the blood. It is transported along axons complexed with a specific carrier protein called neurophysin. The site of storage and subsequent secretion is the posterior pituitary gland (neurohypophysis). The anterior pituitary gland (adenohypophysis) is not involved in this process.
The release of vasopressin into the bloodstream is strictly regulated. The main stimuli for its secretion include:
- An increase in sodium ion ($Na^+$) concentration and total plasma osmolarity (detected by hypothalamic osmoreceptors).
- A decrease in circulating blood volume or a drop in blood pressure (detected by volume receptors).
- Additional factors: angiotensin II, stress, and pain.
This system operates via negative feedback: as soon as blood osmolarity drops or blood pressure rises, ADH secretion is inhibited.
Cellular Mechanism of Action
Normally, the cells of the distal tubules and collecting ducts of the kidneys are virtually impermeable to water. Vasopressin alters this by activating the adenylate cyclase system.
Specific $V_2$ receptors are located on the basolateral membrane of renal epithelial cells. The signal transduction process involves the following steps:
- Vasopressin binds to the $V_2$ receptor.
- The $G_s$ protein is activated, which in turn turns on the enzyme adenylate cyclase (AC).
- Adenylate cyclase catalyzes the formation of the secondary messenger cAMP (from ATP).
- cAMP activates protein kinase A (PKA).
- Active PKA phosphorylates regulatory proteins that act as transcription factors.
- Gene expression for the aquaporin-2 protein is induced in the nucleus.
Synthesized on mRNA templates, aquaporin-2 is transported in vesicles to the apical membrane (facing the lumen of the renal tubule) and is inserted into it, forming specific water channels. Through these channels, water freely diffuses from the tubular fluid into the cell, and from there back into the bloodstream.
Physiological Effects
The action of vasopressin is mediated through two types of receptors, determining its systemic effects:
- Via $V_2$ receptors (in the kidneys): The water permeability of the distal nephron increases dramatically. Facultative water reabsorption is enhanced, leading to a decrease in daily urine output (to a normal 1–1.5 L/day) and an increase in urine density (concentration). Simultaneously, plasma osmotic pressure decreases due to a "dilution" effect.
- Via $V_1$ receptors (in vascular smooth muscle): At high hormone concentrations, it causes constriction of arterioles (vasoconstriction), which contributes to an increase in blood pressure.
Without ADH, urine cannot be concentrated at all, and the body loses colossal volumes of fluid—up to 20 liters per day.
Pathology: Nephrogenic Diabetes Insipidus
Malfunctions in the vasopressin system lead to severe disturbances in water-electrolyte homeostasis. One such condition is nephrogenic diabetes insipidus.
A key distinction between this disorder and ordinary diabetes mellitus is completely normal insulin levels. In nephrogenic diabetes insipidus, the pituitary gland secretes adequate or even elevated amounts of ADH, but the $V_2$ receptors in the kidneys are insensitive to it.
Characteristic symptoms:
- Polyuria (abnormally high daily urine volume).
- Polydipsia (intense, unquenchable thirst).
- Low specific gravity of excreted urine (since water is not reabsorbed and dilutes the urine).