The Pituitary Gland 2 The Posterior Lobe Neurohypophysis Embryological derivation and general structure The posterior lobe of the pituitary gland is derived from a downward growth of neural tissue from the developing brain The posterior pituitary is comprised of the nerve axons descending through the pituitary stalk from their cell bodies in the hypothalamus and numerous glial cells called pituicytes which make up the bulk of the neural lobe Also called the neurohypophysis Separated from the adenohypohysis by an intermediate lobe fairly non existent in humans cid 127 Magnocellular unmyelinated neurons with swellings along the axons called Herring bodies Fenestrated capillaries allow for passage of molecules released from the nerve endings into the general circulation Neurons are described as being either vasopressinergic approximately 80 or oxytocinergic The paraventricular nuclei unlike the supraoptic nuclei are composed of both magnocellular and parvocellular neurons which project either to the median eminence or to other parts of the brain Act as hormones on their target cells in the adenohypophysis the main one being vasopressin which acts as a corticotrophin releasing factor The parvocellular axons going to other parts of the CNS release their neurosecretions across synapses to other neurons act as neurotransmitters Synthesis storage release and transport of neurohypophysial hormones Vasopressin and oxytocin are both nonapeptides synthesized in the neuronal cell bodies of the hypothalamic SON and PVN Pro vasopressin is processed into vasopressin a 93 amino acid neurophysin II and and a 39 amino acid glycopeptide called copeptin Pro oxytocin is similarly processed within the vesicles to just oxytocin and a slightly different neurophysin I Vesicles are transported down the nerve axons by axoplasmic flow involving the intracellular microtubular network and protein motor molecules kinesin and dynein fuse Calcium ions in conjunction with the microfilament network in the cytoplasm bring about the movement of vesicles towards the cell membrane to which they Release of vesicle contents by exocytosis is accompanied by the separation of hormone from neurophysin in the presence of the more alkaline pH of the extracellular fluid It is believed that the Herring bodies and even undiluted parts of the nerve axon can also release the molecules by exocytosis Potential release of the hormones into the cerebrospinal fluid of the third ventricle could explain some of their central effects particularly in those parts of the brain devoid of vasopressinergic and oxytocinergic neurons cid 127 Overall firing rates increase or decrease with changing stimuli Some degree of local coordination of firing activity in adjacent neurons cid 127 Oxytocin and vasopressin are transported unbound to their target tissues Relatively short half lives approximately 5 minutes Vasopressin VP Receptors and mechanisms of action 3 forms GPCRs cortex the kidneys and the CNS The V1 receptor and its signaling pathways and IP3 calcium calmodulin dependent kinase Vasopressin also has some small affinity for the oxytocin receptor V1a receptor is found in a variety of vasopressin s target tissues including vascular smooth muscle hepatocytes cardiomyocytes platelets the adrenal V1b receptors are found on the corticotrophs of the adenohypophysis the heart lungs thymus mammary glands CNS V2 receptor is found in the principal cells of the renal cortical and medullary collecting ducts and the loops of Henle cid 127 GPCR activates the membrane bound enzyme phospholipase C which catalyzes the hydrolysis of a membrane phospholipid called PIP2 producing DAC IP3 opens calcium channels in intracellular calcium stores such as the ER allowing calcium ions to move into the cytoplasm CREB can be induced by DAG phosphorylates intracellular proteins in the presence of calcium activates PKC The V2 receptor and its signaling pathways The enzyme activated by the GPCR is an adenyl cyclase activates PKA The principal cells of the renal collecting ducts synthesize a vasopressin dependent aquaporin which is essential for the movement of water from tubular fluid into the cells Physiological actions of vasopressin cells in tissues throughout the body Peripheral actions The magnocellular neurons which terminate within the neurohypophysis release vasopressin into the general circulation which transports it to its target The parvocellular neurons terminating on the walls of the primary capillary plexus in the median eminence release vasopressin into the hypothalamo adenohypophysial portal system which transports it to its specific target cells corticotrophs in the anterior pituitary Antidiuretic effect stimulation of the water reabsorption process in the collecting duct dysfunction leads to DI cid 127 Migration of aggraphores vesicles containing AQP2 proteins towards the apical membranes of cells where they are inserted Longer term synthesis of new AQP2 molecules via the activation of CREB which enters the cell nucleus and promotes gene expression Degradation or recycling of V2 receptor via beta arrestin activation Additional synthesis of another aquaporin AQP3 which enables water to leave the cell via the basolateral membrane cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 Other renal effects stimulation of sodium and chloride reabsorption from the ascending limb of the loop of Henle and the stimulation of reabsorption in the thin descending limb of the loop of Henle and the collecting duct Vasoconstrictor activity in situations such as dehydration hemorrhage or other conditions of volume depletion the pressor effect of vasopressin is of physiological relevance in maintaining or raising blood pressure to normal levels Blood coagulation stimulation of molecules which participate in coagulation namely Factor VIII and the von Willebrand factor vasopressin used in Hepatic glycogenolysis contributes to the increase in the blood glucose concentration which is an essential element of the normal stress response Adenohypophysial action stimulate corticotrophin release Vasodilator activity in the kidneys treatment of hemophilia Central actions plasma Vasopressin is released from dendrites