Physiology, Posterior Pituitary


Article Author:
Hiran Patel


Article Editor:
Vivekanand Tiwari


Editors In Chief:
Stephen Leslie
Karim Hamawy


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Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
10/27/2018 12:31:48 PM

Introduction

The pituitary gland has two embryological origins. The first being the ectodermal layer that later transforms into the anterior pituitary, the other is the neuroectoderm which forms the posterior pituitary gland. The posterior pituitary is similar to the anterior, where they both ultimately control endocrine function and the body’s hormonal response to the environment. This takes place when the hypothalamus receives neural signals from the brain and secretes polypeptide and neuropeptide hormones which are then transported down the axon for storage in the posterior pituitary gland until they are ready for release. The posterior pituitary hormones are in charge of regulating water retention and inducing uterine contraction.[1]

Cellular

The posterior pituitary gland secrets ADH and oxytocin hormones which are synthesized in the hypothalamus and are released into the neurohypophyseal capillaries which surround the gland. Antidiuretic hormone (ADH) is synthesized in the supraoptic nuclei of the hypothalamus while oxytocin is synthesized in the paraventricular nuclei of the hypothalamus. Both hormones are packaged in secretory granules and travel down the axon where they are stored in the Herring bodies. In contrast to the posterior pituitary, the anterior pituitary hormones are not stored. Instead, they are secreted into the surrounding capillaries moments after being synthesized by the hypothalamus. Once the hormones are released into the systemic circulation, they bind to their respective target sites and prevent diuresis and stimulate lactation and/or uterine contraction.[2]

Development

The pituitary gland, which is attached to the hypothalamus by the pituitary stalk, develops from two embryological sources known as the ectoderm diverticulum and neuroectoderm as stated above. Adenohypophysis, or the anterior pituitary gland, develops from Rathke’s pouch which grows superiorly from the roof of stomodeum. Neurohypophysis, also called the posterior pituitary gland develops from the neuroectodermal layer called infundibulum. This grows inferiorly from the floor of the diencephalon. In approximately 35 to 40 days of gestation, Rathke’s pouch transforms into a vesicle that flattens itself, surrounding the anterolateral surface of the infundibulum and eventually detaching itself from the stomodeum. The proliferation of the infundibulum diverticulum ultimately generates the cells that make up the neurohypophysis or posterior pituitary.

Function

Antidiuretic Hormone (ADH)

ADH, also known as vasopressin, acts as a water preserving hormone. ADH is released into the blood circulation to vasoconstrict and reabsorbs water from the collecting duct in the kidney to maintain equilibrium intracellularly and extracellularly. In the hypothalamus, there are two regulating receptors that sense water depletion and hyperosmolar concentration, the subfornical organ, and organum vasculosum. This particular area of the nervous system does not have an intact blood-brain barrier. Therefore, blood products can come into contact with the structures with ease and eventually signal the hypothalamus for ADH secretion. A small concentration is enough to generate water conservation in the renal tubules. The renal tubules are broken down into segments known as the proximal, descending, ascending, distal, and collecting duct. The collecting duct is a highly diluted, ADH dependent structure in the kidney. The cells in the collecting duct have a 7 pass receptor on the basolateral side where ADH can bind itself. The signal unleashes a power generating cascade known as cAMP. The Gs protein stimulates adenylyl cyclase, which converts ATP into cAMP. High concentration of cAMP will phosphorylate protein kinase A, opening water channels to allow passage from the luminal side to the basolateral side. The channels are gated vesicles known as aquaporins. The amount of water absorbed from the collecting duct is dependent on the amount of fluid loss.[3][4][5]

Oxytocin

Oxytocin is a polypeptide hormone that is produced in the paraventricular nuclei for storage and release from the pituitary gland. It is commonly excreted in females during the birthing process. It functions to allow the uterus to contract, release milk from the breast and is present during ejaculation in males.[6]

Oxytocin: Uterus

When the fetus reaches an appropriate size, it stretches the uterine muscle lining, transmitting signals to the hypothalamus which generates and releases oxytocin into the systemic circulation. The hormone binds to the myometrial layer of the uterus where the smooth muscle is present. Once oxytocin attaches to the extracellular receptor, it activates the Gq protein, which then activates another cell membrane protein called Phospholipase C. PLC will break down phosphoinositol diphosphate in two components, diacylglycerol (DAG)  and Inositol triphosphate (IP3). IP3 will push calcium from the sarcoplasmic reticulum while DAG activates protein kinase C. This protein will phosphorylate proteins on the cell membrane to specifically allow calcium entry from extracellular space. An increase in intracellular calcium will generate enough energy to cause contraction of the uterus advancing the fetus into the vagina for delivery.

 Oxytocin: Lactation

The regulation of lactation is similar to uterine contraction where an external source stimulates the production of oxytocin by the hypothalamus. During lactation, the newborn, by means of “suckling”, will transmit a signal to the central nervous system. This process is known as the “milk letdown reflex.” Once oxytocin binds to myoepithelial cell receptors in the breast it will undergo the same Gq cascade as uterine contraction, ejecting milk forward into the baby’s oral cavity.

Oxytocin: Ejaculation

A similar concept holds for sexual orgasmic response in males. During ejaculation, the oxytocin contracts the vas deferens to push the sperm and semen forward for ejection.

Pathophysiology

Hyposecretion

Central Diabetes Insipidus (CDI)

CDI is the most common form of pathology secondary to low ADH secretion by the posterior pituitary. Decreased levels of ADH will increase the number of binding receptors in the collecting duct. However, this will result in excess free water in the urine. Approximately 50% of the cases have no clear etiology and therefore, are labeled as idiopathic central diabetes insipidus. The other 50% belong to different categories including familial, traumatic and various disorders of hypothalamus, pituitary, for example, Sheehan syndrome, tumors, sarcoidosis, tuberculosis, syphilis, eosinophilic granuloma, and/or encephalitis.[3]

Oxytocin Insufficiency

Hyposecretion of oxytocin is not a common pathology but does transpire on rare occasions. This occurs when the level of oxytocin is well below the baseline margins. Low levels of oxytocin would halt uterine contraction and milk ejection during the birthing process. Panhypopituitarism is a condition where all anterior and posterior pituitary hormone levels are below normal, compromising their respective organs and can potentially be the cause of oxytocin insufficiency.[6]

Hypersecretion

Syndrome of Inappropriate Antidiuretic Hormone

SIADH is excess ADH production from the posterior pituitary or from an ectopic source. Elevated levels result in excess water retention and hypervolemic hyponatremia. However, edema or third spacing does not occur because hypervolemia activates natriuresis, which excretes water from the urine. SIADH also inhibits the production of renin and aldosterone secondary to volume expansion and high blood pressure, leading to diuresis. SIADH etiologies are tumors, malignancies, stroke, trauma, infection, medications, and/or anesthesia.[7]

Oxytocin Toxicity

This is a very rare situation and occurs when the level of oxytocin is above the baseline margins. High concentrations of oxytocin result in an overactive uterus causing hypertrophy and limiting pregnancy due to insufficient space to hold the fetus.

Clinical Significance

Central versus Peripheral Diabetes Insipidus

Patients with CDI and PDI present with excessive diluted urine (polyuria) and thirst (polydipsia). If the patient has an impaired thirst drive they may present with mild hypernatremia. Differentiating CDI and PDI requires checking urine osmolality and a water deprivation test. In Psychogenic polydipsia, the urine osmolarity will return to baseline within a couple hours after a water deprivation test. However, if the osmolarity continues to trend below baseline then injecting 2 g of desmopressin (vasopressin agonist) would be the next step. In central diabetes insipidus, the urine osmolarity should slowly return to baseline a couple of hours after administering desmopressin. In peripheral diabetes insipidus, there will be no change in urine osmolarity despite administration of desmopressin. The long-term treatment for CDI is desmopressin via nasal spray, orally, or subcutaneous injections. As for PDI, long-term treatment is with sodium depletion, thiazide diuretics, and removal of any offending agents, like lithium. Studies have shown that removing electrolytes from the body will lead to increase reabsorption of sodium and water in the proximal tubules.[3][4]

Syndrome of Inappropriate Antidiuretic Hormone  

SIADH is a diagnosis of exclusion once all other causes of hyponatremia have been ruled out. Treatment depends on the status of the patient, if asymptomatic then water restriction is sufficient. If this treatment fails to improve the sodium level, then add lithium or demeclocycline. Both agents antagonize antidiuretic hormone, which will induce diuresis and ultimately correct the sodium level. ADH receptor antagonists like tolvaptan and conivaptan are also approved for treatment of SIADH. In symptomatic patients, first-line treatment depends on the severity of the symptoms.[3][7]


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Physiology, Posterior Pituitary - Questions

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Which endocrine hormone is released from the posterior pituitary gland?



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Select the choice that describes the pathway that hormones from the hypothalamus reach the pars distalis.



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A 45-year-old male with a history of hypertension on lisinopril, type 2 diabetes mellitus on metformin, and bipolar disorder on lithium presents with complaints of polyuria and polydipsia for several months. Urinalysis shows low specific gravity and decreased urine osmolarity even after water restriction and injecting 2 g of vasopressin. What is the most likely diagnosis and pathophysiology of this patient's current condition?



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Where in the endocrine system are vasopressin and oxytocin stored?



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A 39-year-old female recently had an MRI following several months of early morning headaches, which showed a mass compressing the paraventricular nuclei. Which of the following hormones will be secreted in excess?



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Physiology, Posterior Pituitary - References

References

Larkin S,Ansorge O, Development And Microscopic Anatomy Of The Pituitary Gland null. 2000     [PubMed]
Brown CH, Magnocellular Neurons and Posterior Pituitary Function. Comprehensive Physiology. 2016 Sep 15     [PubMed]
Agus ZS,Goldberg M, Role of antidiuretic hormone in the abnormal water diuresis of anterior hypopituitarism in man. The Journal of clinical investigation. 1971 Jul     [PubMed]
Morgan RJ,Martyn JA,Philbin DM,Coggins CH,Burke JF, Water metabolism and antidiuretic hormone (ADH) response following thermal injury. The Journal of trauma. 1980 Jun     [PubMed]
Pillai BP,Unnikrishnan AG,Pavithran PV, Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder. Indian journal of endocrinology and metabolism. 2011 Sep     [PubMed]
Gimpl G,Fahrenholz F, The oxytocin receptor system: structure, function, and regulation. Physiological reviews. 2001 Apr     [PubMed]
Hew-Butler T,Hummel J,Rider BC,Verbalis JG, Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise. American journal of physiology. Regulatory, integrative and comparative physiology. 2014 Aug 15     [PubMed]

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