Posterior Pituitary

Introduction

The posterior pituitary functions as a neuroendocrine interface where hypothalamic neurons synthesize and release key hormones. Antidiuretic hormone is primarily regulated by osmolality, while oxytocin and antidiuretic hormone act through neurohumoral reflexes, with clinical relevance in conditions such as inappropriate secretion states.

• The posterior pituitary releases antidiuretic hormone and oxytocin into circulation. These hormones are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus.
• They are termed neurohormones because they are produced by neurons and released into blood.

Antidiuretic Hormone

Antidiuretic hormone regulates body water balance, blood volume, and arterial pressure.

Structure, Synthesis and Secretion

Structure and Source

• It is also called vasopressin and is a peptide with nine amino acids.
• It is synthesized in magnocellular neurons of the supraoptic and paraventricular nuclei, mainly in the supraoptic nucleus.

Synthesis of ADH

• Antidiuretic hormone is synthesized in cell bodies of the supraoptic and paraventricular nuclei of the hypothalamus. It is produced initially as a preprohormone, which is processed into a prohormone and then the active hormone.
• The precursor molecule contains antidiuretic hormone, neurophysin two, and a glycoprotein component. These components are formed from genes located on chromosome twenty.
• Enzymatic cleavage separates the active hormone, carrier protein, and associated glycoprotein.
• The hormone is packaged with neurophysin two into secretory granules within the Golgi apparatus.
• Neurophysin acts as a carrier, facilitating transport of the hormone along neuronal axons.
• The granules, known as Herring bodies, move by axoplasmic transport toward the posterior pituitary.
• The axon terminals store these granules until appropriate stimuli trigger hormone release.

• This coordinated process ensures efficient synthesis, transport, and availability of antidiuretic hormone for physiological regulation.

Regulation of Secretion

Antidiuretic hormone secretion is mainly regulated by plasma osmolality and extracellular fluid volume.

Plasma Osmolality

• Plasma osmolality is the most sensitive stimulus for hormone release.
• An increase above about 285 milliosmoles per kilogram stimulates hypothalamic osmoreceptors. These receptors are located in the anterior hypothalamus.
• Even a one percent rise in osmolality significantly increases hormone secretion.
• The hormone promotes water reabsorption, thereby restoring normal osmotic balance.

Blood Volume and Pressure

• Changes in blood volume and arterial pressure also influence secretion.
• A decrease in mean arterial pressure leads to increased hormone release.
• Reduction in extracellular fluid volume further enhances secretion. However, osmolality remains a stronger stimulus than volume changes.
• Hypovolemia increases sensitivity of the hormone response to osmotic changes. This ensures effective conservation of water during fluid loss.
• Activation of the renin angiotensin system contributes to regulation during volume depletion.
• Angiotensin two stimulates thirst centers and promotes water intake.
• Specific brain regions involved include the subfornical organ and organum vasculosum of lamina terminalis. These structures are located outside the blood brain barrier, allowing rapid detection of circulating signals.
• This integrated control maintains fluid balance and circulatory stability.

Factors Affecting ADH Secretion

Factors that Increase ADH Secretion

• Antidiuretic hormone secretion increases with elevated plasma osmolality, reduced extracellular fluid volume, and low blood pressure.
• It is also stimulated by angiotensin two, pain, nausea, stress, hypoglycemia, and increased body temperature.

Stimuli that Inhibit ADH Secretion

• Antidiuretic hormone secretion decreases with low plasma osmolality and increased extracellular fluid volume.
• Ethanol, cortisol, atrial natriuretic peptide, thyroxine, reduced temperature, and alpha adrenergic stimulation inhibit secretion.

Metabolism

Antidiuretic hormone is rapidly metabolized in the liver and kidneys. Its biological half life is approximately eighteen minutes in humans.

Mechanism of Action

Antidiuretic hormone regulates water balance and vascular tone by acting on specific receptors in kidneys and blood vessels.

ADH Receptors

Two main receptor types are V2 receptors and V1 receptors.

V2 Receptors

• V2 receptors are located on epithelial cells of distal convoluted tubules and collecting ducts.
• Activation of these receptors increases intracellular cyclic adenosine monophosphate. This activates protein kinase, leading to phosphorylation of cellular proteins.
• Vesicles containing aquaporin channels move to the luminal membrane.
• Aquaporin two channels are inserted into the membrane, increasing water permeability. This enhances water reabsorption and reduces urine output.
• Aquaporins are specialized water channels present in various tissues.

Aquaporins

Aquaporin one, two, and three are found in the kidney, while others are distributed in brain, glands, and immune cells. These channels facilitate rapid water movement across cell membranes.

V1 Receptors

• V1 receptors are present in vascular smooth muscle and certain brain regions.
• V1A receptors mediate vasoconstriction, increasing peripheral resistance and blood pressure. This effect is produced by activation of phospholipase C and rise in intracellular calcium.
• V1B receptors are present in the pituitary and regulate hormone secretion. They stimulate release of corticotropin releasing hormone and adrenocorticotropic hormone.
• Through these mechanisms, antidiuretic hormone maintains fluid balance, blood pressure, and supports stress responses.

Functions of ADH

• Antidiuretic hormone primarily increases water reabsorption in the distal convoluted tubule and collecting duct. It is released during hypovolemia, hypotension, and increased plasma osmolality. This action helps restore extracellular fluid volume in conditions such as dehydration and fluid loss.
• It causes vasoconstriction at higher concentrations, thereby increasing arterial pressure.
• Water conservation occurs at physiological levels, whereas vascular effects require higher levels.
• In the central nervous system, it acts as a neurotransmitter and supports memory functions.
• It also influences autonomic centers and modulates neural activity.
• It promotes contraction of smooth muscle in the reproductive tract, aiding ejaculation.
• It stimulates release of corticotropin releasing hormone and enhances adrenocorticotropic hormone secretion.
• It can reduce cardiac output through central mechanisms.
• It also promotes glycogen breakdown in the liver, contributing to energy availability.

Applied Physiology

Diabetes Insipidus

• Diabetes insipidus results from deficiency or impaired action of antidiuretic hormone. It is characterized by excretion of large volumes of dilute urine.
• The common causes include hypothalamic or posterior pituitary dysfunction.
• Two forms are recognized: central type due to reduced hormone secretion and nephrogenic type due to renal unresponsiveness.
• Major clinical features are polyuria and polydipsia.
• Excess urine output leads to dehydration, which triggers increased thirst.
• Urine in this condition is markedly dilute, with osmolality usually less than 300 milliosmoles per liter. This distinguishes it from diabetes mellitus, where urine is concentrated due to glucose excretion.
• In nephrogenic type, kidneys fail to respond to circulating hormone.
• In central type, hormone production or release is deficient.
• Early diagnosis and appropriate management are essential to prevent dehydration and electrolyte imbalance.

Nephrogenic DI

Etiology and Types

• Nephrogenic diabetes insipidus occurs when kidneys fail to respond to antidiuretic hormone despite normal secretion.
• The defect involves impaired V2 receptors or abnormal aquaporin channels in renal tubules.
• Acquired causes include drugs such as lithium, aminoglycosides, and certain chemotherapeutic agents.
• It may also result from metabolic disorders like hypercalcemia and hypokalemia.
• Renal ischemia and infiltrative diseases can further impair tubular response.
• Genetic forms include X linked defects affecting V2 receptors and autosomal defects involving aquaporin channels.
• These abnormalities reduce water reabsorption and produce dilute urine.

Treatment

Treatment focuses on improving renal sensitivity to the hormone and correcting underlying causes.

Neurogenic DI

Etiology and Types

• Neurogenic diabetes insipidus results from deficient hormone production due to central nervous system disorders.
• Causes include head injury, tumors, infections, vascular lesions, and congenital defects.
• Damage may involve the hypothalamus, neural pathways, or posterior pituitary.
• This leads to reduced hormone release and impaired water conservation.

Treatment

• Treatment includes administration of desmopressin, a synthetic analogue that acts on V2 receptors. It effectively increases water reabsorption and reduces urine output.
• Other supportive therapies may also improve symptoms and fluid balance.

Syndrome of Inappropriate ADH Secretion

• Syndrome of inappropriate antidiuretic hormone secretion is characterized by excessive hormone release despite low plasma osmolality. It results in inappropriate water retention and dilution of plasma solutes.
• Common causes include head injury, neurological disorders, and certain medications. It may also occur due to ectopic hormone production by malignancies, especially lung tumors.
• Excess hormone action increases water reabsorption in kidneys, leading to dilutional hyponatremia.
• Expansion of extracellular fluid suppresses aldosterone secretion, promoting sodium loss in urine. This combination produces both water retention and natriuresis.
• Clinical features include low plasma sodium concentration and reduced plasma osmolality.
• Urine remains concentrated despite hypotonic plasma.
• In neurological conditions, the disorder may present as cerebral salt wasting.
• When associated with pulmonary diseases, it is termed pulmonary salt wasting.
• Early recognition is essential to prevent complications such as neurological dysfunction due to hyponatremia.

Oxytocin

Structure, Synthesis and Secretion

Source and Synthesis

• Oxytocin is a nine amino acid peptide synthesized in magnocellular neurons of the hypothalamus. It is produced mainly in the paraventricular nucleus, with minor contribution from the supraoptic nucleus.
• After synthesis, it is transported to and stored in the posterior pituitary.
• The precursor molecule contains oxytocin, neurophysin one, and a glycoprotein.
• Its synthesis, transport, and release mechanisms are similar to those of antidiuretic hormone.

Regulation of Secretion

• Secretion is stimulated by suckling during breastfeeding and by cervical stretch during labor.
• Genital stimulation and certain stressors can enhance release.
• Alcohol inhibits oxytocin secretion.

Functions

• Oxytocin mediates the milk ejection reflex by causing contraction of myoepithelial cells in mammary glands.
• It also facilitates uterine contractions during parturition, aiding delivery.

Milk Ejection Reflex

The milk ejection reflex is the expulsion of milk from mammary glands during suckling.

Receptors

It is initiated by stimulation of tactile receptors in and around the nipple.

Reflex Arc

• Suckling generates sensory impulses that travel to the spinal cord and ascend to higher centers.
• These signals reach the hypothalamus and activate oxytocin secreting neurons.
• Neural pathways relay information efficiently to coordinate hormone release.
• The hypothalamus stimulates release of oxytocin from the posterior pituitary into circulation.
• Oxytocin reaches the mammary glands through the bloodstream. It acts on myoepithelial cells surrounding the milk producing alveoli. These cells contract and push milk from alveoli into the ductal system. Milk is then propelled toward the nipple and delivered to the infant.

Effects

• This reflex is rapid and coordinated, ensuring effective feeding.
• Emotional and sensory factors can influence its efficiency.
• Proper functioning of this reflex is essential for successful breastfeeding and infant nutrition.

Physiological Significance

• The milk ejection reflex is a classic neurohumoral reflex involving neural and hormonal pathways.
• Similar mechanisms are observed in certain animals, where ovulation is triggered by mating stimuli.

Parturition Reflex

• Oxytocin plays a key role in the parturition reflex by stimulating uterine contractions.
• Near term, oxytocin secretion increases and uterine receptor density rises.
• Enhanced hormone levels and receptor sensitivity produce strong rhythmic contractions. These contractions facilitate expulsion of the fetus during childbirth.
• The parturition reflex is a neurohumoral reflex, involving neural signals and hormonal action.
• Oxytocin receptors are also present in the ovary. It may contribute to regression of the corpus luteum at the end of the cycle.
• In males, oxytocin secretion increases during orgasm. It may assist contraction of smooth muscle in the vas deferens, aiding sperm transport.
• In females, oxytocin induces uterine contractions after deposition of semen. These contractions help movement of sperm toward the fallopian tubes. This action supports fertilization along with intrinsic sperm motility.

Applied Physiology

• Oxytocics are synthetic preparations of oxytocin used in obstetric practice. They are administered to induce labor when contractions are inadequate at term.
• Controlled infusion helps strengthen and coordinate uterine contractions during labor.
• After delivery, oxytocics are given to prevent postpartum hemorrhage by promoting uterine contraction and compressing bleeding vessels.