Gland: Posterior Pituitary

THE PITUITARY GLAND

The pituitary, the existence of which has been known for 2000 years, sits in the sella turcica of the sphenoid bone. The sella turcica forms the roof of the sphenoid sinus. The lateral walls are comprised of durra or bone, which abut the cavernous sinuses and can affect the 3rd, 4th, and 6th cranial nerves and the internal carotid arteries since they transverse thru this area.
The cavernous sinuses can exert a great deal of CSF pressure but, due to the diaphragm sellae, the gland will not become compressed nor will the optic chiasm and tracts, which lie immediately above the diaphragm sellae. Also lying in close proximity to the cavernous sinuses are the internal carotid arteries, cranial nerves 3, 4, 5 and 6, the third ventricle and the optic chiasm, which lies above the diaphragm sellae.
The pituitary is divided into three parts:

1. ADENOHYPOPHYSIS-is the anterior portion, which is derived from Rathke’s pouch. This is divided into three lobes: the pars distalis (anterior lobe,) the pars intermedia (intermediate lobe) and the pars tuberalis.

2. NEUROHYPOPHYSIS-is the posterior portion and is composed of the pars nervosa, the infundibular stalk, and the median eminence. The major supply of axons to the neural lobe is the magnocellular secretory neurons from the paraventricular and supraoptic nuclei of the hypothalamus. These axon terminals also secrete AVP (regulating blood osmolarity, pressure, and fluid balance) and oxytocin into the surrounding capillary beds leading into the hypophyseal veins. The infundibular stalk is surrounded by the pars tuberalis, and together they make up the hypophyseal stalk.

3. VESTIGIAL INTERMEDIATE LOBE
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The pituitary gland is regulated by the hypothalamus via feedback mechanisms of hormones and from paracrine and autocrine secretions from the pituitary itself. It attaches to the hypothalamus via the stalk thru the diaphragm sellae and into the median eminence.

The pituitary is derived from the:
• ECTODERM-which forms the pars distalis/tuberalis and the intermediate lobe
• NEURAL PORTION-which forms the infundibulum, posterior pituitary, and neural stalk
The pituitary weighs between 4-900 mgs (during pregnancy up to 1 gram), is bean shaped and brownish in color with dimensions of 9 mm A/P, 6mm S/I, 13 mm laterally. The hypothalamus receives its blood supply from the superior (provides 10-20 % of the blood supply) and inferior hypophyseal arteries (supply blood to the posterior pituitary), which are derived from the internal carotid arteries. These arteries form a capillary network in the median eminence (external to the blood-brain barrier).
This capillary network picks up hypothalamic secretions from the hypothalamic nerve endings delivering them into the long and short hypophyseal portal veins, which are now transported to the anterior pituitary. Please note that retrograde blood flow causes bi-directional movement of blood between the hypothalamus and pituitary. Once the hypothalamic releasing hormones reach the pituitary, they activate G protein receptors on the cell membrane, creating a cascading chain reaction for the production of their pituitary hormone counterparts. Blood drainage of the pituitary leaves through the cavernous sinuses and the petrosal veins and out the jugular foramina via the jugular vein. Note that the blood supply to the pituitary via the hypothalamus is not unidirectional and can flow both ways creating ultra-short biofeedback loops.
The hypothalamus releases its secretions via hypothalamic neurons, which end in the infundibulum and permeate into the fenestrations at the perigomitolar capillaries. This enters the portal vein, which enters the capillary circulation of the anterior pituitary (which provides 80-90 % of the blood supply to the pituitary). The pituitary, as stated above, is attached to the hypothalamus via the pituitary infundibulum.
The diaphragm sellae has a 5mm opening for the hypophyseal stalk and allows transmission of pulsations of CSF. The purpose of the pituitary infundibulum is to act as a direct pathway for hormonal secretion between the hypothalamus and the pituitary. Pituitary hormones are released as pulsations, which does affect hormonal levels minute, by minute, which may give false positives when measuring hormonal levels.
Each releasing factor (hormone) that is released from the hypothalamus causes a release of a hormone from the anterior pituitary. The hypothalamus also produces two hormones called antidiuretic hormone and oxytocin. Anti-diuretic hormone is formed primarily by the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei. The major nerve tracts of the neurohypophysis arise from these two nuclei, from large cells termed magnocellular cells forming the supra optico hypophyseal tract and the paraventricular hypophyseal tract. AVP and oxytocin tracts are also distributed widely and project into the brain stem affecting the vagal nuclei, glossopharyngeal nuclei, and the spinal cord, sending information to the ANS to evaluate blood pressure. Vasopressinergic and oxytocin fiber pathways (which have different effects than those that end in the posterior pituitary) also terminate in the choroid plexus, which influences salt and water exchange between the brain (especially regions associated with emotion and memory) and the CSF.
Neurological impulses from the two nuclei above, cause secretory granular release of these two hormones into the posterior pituitary, which are then released into the adjacent capillaries. It is interesting to note that the differences between oxytocin and anti-diuretic hormone are two amino acids. Otherwise, the chains are identical. The functions are entirely different, as you will see.
The anterior pituitary is controlled by the hypothalamus in a slightly different manner than the posterior pituitary. Oxytocin and anti-diuretic hormone (AVP) are produced in the hypothalamus and are released into the posterior pituitary, via the neurological tracts of those nuclei mentioned above in the hypothalamus. Other neurological tracts secrete other neuropeptides called TRH (thyrotrophin releasing factor), CRH (corticotrophin releasing hormone), VIP and neurotensin. Paraventricular hypophyseal tracts located on either side of the ventricles are both unmylenated and descend thru the infundibulum. The releasing factors from the hypothalamus are transmitted to nerve endings, which then release these factors into a primary plexus of veins known as the hypophyseal portal system. These veins are located in the pituitary infundibulum and travel into the anterior pituitary, releasing the hypothalmic hormones into and stimulating the anterior pituitary.

THE POSTERIOR PITUITARY
(NEUROHYPOPHYSIS, INFUNDIBULAR PROCESS)

The posterior pituitary includes the pars nervosa, infundibular stalk, and the median eminence, and is directly innervated by the supraoptic hypophyseal and the tuber hypophyseal neurological tracts. The median eminence, which lies in the tuber cinereum, has an internal zone from which the supraoptic and paraventricular magna cellular neurons control the posterior pituitary and an external zone, which receives information from the hypophyseal trophic neurons (sensory trophic neurons.) The magnocellular neurons embrionically arise out of neuroepithelial cells lining the third ventricle, which form the supraoptic nuclei above the optic chiasm, and the paraventricular nucleus located in the third ventricle.
A third structure, which is also considered part of the median eminence, is the pars tuberalis, which surrounds the infundibulum and pituitary stalk. The median eminence is composed of nerve endings and blood vessels and is truly the functional link between the hypothalamus and the pituitary. The median eminence receives blood supply from the posterior communicating and superior hypophyseal artery (from the internal carotid) and drains thru the cavernous sinuses.
The blood then flows thru capillary loops, which anastomose and drain into the sinusoids, which become the pituitary portal veins. The pituitary portal veins drain into the pituitary, the neural stalk and specialized neuro tissues that lie at the base of the hypothalmic pituitary juncture. This forms the base of the third ventricle, creating a funnel (infundibulum), and literally draining into the CSF as well as releasing neurosecretions into the anterior pituitary.
The 2 major hypothalamic/posterior pituitary nerve tracts, which arise from magnicellular cells, are the bilateral supraoptic nucleus and the paraventricular nucleus and they produce (via ribosome protein synthesis) a pre-prohormone. Then, via glycosylation in the Golgi apparatus, the pre-prohormone is made into the prohormone and transported via neurosecretory granules (inactive state), where the secretory granular membrane adheres to the plasma membrane, releasing the granular material into the cell. It is then stored in the posterior pituitary as a neurophysin.
Then, through the process of exocytosis, anti-diuretic hormone (AVP) and neurophysin 2 are released via neuron bombardment into the blood stream. There are two receptor sites: V1 found in smooth muscle, and V2 found in renal epithelial. V2 activates antidiuretic activity by activation of adenylate cylclase.
Once the neurophysin is cleaved, the hormones are released. Capillaries and glue like non-secretory cells (pituicytes) help bind together the posterior pituitary. The capillaries are different in that they allow diffusion of the neurosecretory cells into the blood stream, unlike other capillaries in the brain that are subject to the blood brain barrier, preventing diffusion into circulation. The purpose of the posterior pituitary is to regulate body cell osmolarity by regulating sodium concentration, and by effective extracellular fluid regulation via osmoreceptors.
Osmoreceptors for thirst and AVP release respond to slight changes in extracellular fluid osmolarity. The primary osmoreceptors that are triggered are triggered by urea and glucose for sensing changes in osmolarity and are found in the brain and outside the blood brain barrier. For example, an increase in ECF (extracellular fluid) osmolarity causes shrinkage of the cells, stimulating the osmoreceptors inside the cells to stimulate the release of AVP and angiotensin 2, conserving H20. Bar receptors are of two types:
• Low pressure found in the right side and left atrium of the heart
• High pressure found in the carotid sinus and aortic arch. This stimulates the vagus nerve and the glossly pharyngeal to the nucleus tractus solitarius then via noradrengic projections into the PVN and SON, which then inhibits the release of AVP
To a lesser degree, a drop in blood volume stimulates angiotensin 2 and AVP release, stimulating thirst and increasing blood volume. Once blood volume is up, the oropharyngeal reflex and the release of atrial natriuretic peptide suppresses thirst. In actuality, the purpose then becomes regulating cell volume against extracellular fluid. The goal is to create a balance in Intra and extracellular osmolarity, whereby permeability would be perfect for passive and active transport (keeping the highways open between the cells and the extracellular fluids they bathe in.) This allows cell metabolites, CO2, hormones, enzymes and antibodies to diffuse with ease out of the cell while letting food, enzymes, hormones and oxygen to enter the cell.
From an active standpoint, sodium constantly leaks into the cell, and potassium leaks out of the cell. This is due to their respective concentration gradients. Via active transport, the sodium-potassium ATPase extrudes the sodium to outside the membrane, and at the same time potassium is pulled back in. As potassium is leaking out via passive diffusion, it is being pulled back in via active transport.
The following hormones, which are octal peptides with similar structural formulas, are released from the posterior pituitary:

1. ANTI-DIURETIC HORMONE (AKA VASOPRESSIN, ARGININE VASOPRESSIN, AVP) and its related neurophysin one (propressophysin, prohormone) cause the kidneys to retain water, excrete sodium while retaining potassium, and raising blood pressure through vasoconstriction. The most important factor regulating vasopressin is blood osmolarity and circulating blood volume. Increases in osmolarity and decreases in volume both increase vasopressin release. Blood osmolarity is kept within a fine range +- 1.8% of 282 mmo/kg. Other factors that affect blood osmolarity include emotional stress, nausea and blood pressure.
1) Aldosterone has the opposite effect, as well as constricting blood vessels and elevating blood pressure.
The glucocorticoids and mineral corticoids, released by the adrenal cortex, counteract the function of antidiuretic hormone.
Since glucocorticoids control sugar levels in the body, you can see how diabetes insipidus can occur. AVP release is also enhanced by prostaglandin E 2, morphine, nicotine, acetylcholine, histamine, barbiturates and hypoxia. Other factors that suppress AVP are alcohol and atrial natriuretic peptide.

DIABETES INSIPIDUS

This is a condition where there is a large volume of urine that is dilute (hypotonic) and tasteless (insipidus.) In diabetes mellitus, the urine is hypertonic and sweet tasting like honey (mellitus.)

1. OXYTOCIN AND ITS RELATED NEUROPHYSIN 2 (PROOXYPHYSIN) causes contraction of the uterus during the birth process and causes the contraction of the myo-epithelial cells in the breasts when the baby suckles. Oxytocin is also involved in maintaining the uterus in a quiet state during pregnancy. Oxytocin is also responsible for maternal behavior. Oxytocin is found in the ovary, placenta, testis, renal medulla, thymus and anterior pituitary. Oxytocin may also affect feeding behavior, gonadotrophin secretion, response to stress (decreasing stress), stimulation of the tubules in the spermatic ducts, regulating blood pressure, temperature, and heart rate. Just like AVP, oxytocin release is stimulated by plasma hypertonicity and suppressed by plasma hypotonicity via binding to high-affinity receptors. It stimulates cAMP, which increases natriferic and hydro-osmotic responses of the tissue.
4. 4. The posterior pituitary and the adrenal glands regulate mineral, water and sugar levels in the body. Factors that stimulate oxytocin secretion are nausea, saity, cholecystokinin and angiotensin 2. Factors that inhibit oxytocin are opiods, relaxing and ANP.

Both oxytocin and AVP and their related neurophysin are synthesized in both the supra-optical (most oxytocinergic) (dorsal portion) and vasopressin (ventral portion), which project into the posterior pituitary and via the paraventricular nucleus, which is divided into 3 distinct magno cellular divisions consisting of:
• Oxytocinergic neurons
• Vasopressin neurons
• Par cellular division that synthesizes peptides, corticotrophin releasing hormone, thyrotrophin releasing hormone, somatostatin, and opiods. Projections from pare cellular neurons project into the median eminence, brain stem and the spinal cord for autonomic function. The supra chiasmic nucleus in the third ventricle secretes only vasopressin and controls circadian and seasonal rhythms. Ventricular neurons triggered by nerve action potentials, via cholinergic and noradrenergic neurotransmitters, and several other neuropeptides including angiotension 2, atrial peptide (AP), and atrial natriuretic factor (ANF) cause an influx of calcium. This induces movement of the neuro secretory granules to the membrane surface, causing a release of the hormones from the granules into per vascular space. From there, it enters into the capillary system of the posterior pituitary, or via microtubule tracts. Acetylcholine stimulates AVP via nicotinic acid receptor stimulation and oxytocin release where adrenergic influences inhibit oxytocin and AVP secretion thru beta androgenic receptors. They are then transported via vesicles into the axons to the neural lobe. Both hormones and their neurophysins are released in fixed ratios.

Other substances released from the posterior pituitary include:
• Somatostatin
• SRIF (somatotrophin release inhibiting factor)
• TRH
• Substance P
• LHRH
• GNRH (gonadotrophin- releasing hormone)
• Dopamine
• Serotonin
• Histamine
• Beta-melanocyte-stimulating hormone (b-MSH)
• An opium peptide named dynorphin a 1-8, which is present in AVP-containing neurons

From a biochemical perspective, the posterior pituitary controls biochemistry by maintaining potassium levels in all cells. As you may already be aware, potassium levels are highest within the cell. The purpose of potassium within cells is to maintain water levels. Potassium has been coined the “oxidative life principle” of the body. If this balance is affected, cells can either burst or shrink.
In so doing, potassium literally pulls foodstuffs (that are stored in the cell membrane) through the membrane of the cell and into the mitochondria for energy. Now, via the demand of the cell, the potassium, which is controlled by the posterior pituitary, donates oxygen to this hydrogenated foodstuff on the membrane and draws it into the cell. When the pressure gradient of potassium becomes too high on the inside of the cell, potassium, along with metabolic waste products, is transported out of the cell. Therefore, by balancing water levels in body, the posterior pituitary can balance the body’s pH.
The posterior pituitary also balances the pH of the body by affecting sugar levels (which are acids) and minerals (which are alkaline). So, in essence, the posterior pituitary, the pancreas, and adrenals dramatically affect the above.

The following blood tests assess the functions of the posterior pituitary:

1. POTASSIUM as mentioned above is the primary indicator for posterior pituitary function.

2. TRIGLYCERIDES are composed of a molecule of glycerol and three molecules of fatty acids. The energy necessary for active transport across a cell membrane, via the influence of potassium, is supplied by fatty acids.

3. GLUCOSE although affected by many other organs and glands, glucose is also affected by the posterior pituitary.

4. BUN/CREATININE RATIO blood urea nitrogen and creatinine are residue byproducts found at the end of protein and muscle metabolism. They are kept in continual balance via the water content in our body. The kidneys flush out the blood urea nitrogen and creatinine when the concentrations get too high, via antidiuretic hormone release from the posterior pituitary.