Diagnosis and Management of Pituitary Tumors

44 GOTH, MAKARA, AND GERENDAImedial nucleus, and, dorsal to it can be found the dorsomedialnucleus. The periventricular nucleus occupies a narrow regionclose to the third ventricle.The mamillary region includes the mamillary bodies and a notwell-defined cell group, the posterior nucleus. These two nuclei donot project to the median eminence. However, the mamillary bodies,because of their rich connection with the thalamus, cerebralcortex, and limbic system, make the HT an integral part of thesecerebral structures.The axons of the arcuate, ventromedial, dorsomedial, andperiventricular neurons, as well as fibers from the parvicellularpart of the paraventricular nucleus, and a small portion of thesupraoptic neurons, project to the superficial zone of the medianeminence. Because the HT hormones are produced by neurons ofthe aforementioned cell groups, these HT nuclei are those that playa determining role in the control of adenohypophysial hormonesecretion (hypophysiotropic neurons). In addition, the preopticarea also contains hormone-producing nerve cells with axons terminatingin the median eminence.The hypophysiotropic neurons also synthesize bioactive substancesother than the HT-releasing and release-inhibiting hormones.Among others, opioid peptides (enkephalin, endorphins,dynorphin), vasoactive peptides (neurotensin, bradykinin, atrialnatriuretic peptide, angiotensin II), and gastrointestinal peptides(vasoactive intestinal peptide, PIT adenylate-cyclase activatingpolypeptide, cholecystokinin, tachykinin, galanin, neuropeptideY) are also produced in hypophysiotropic neurons. A givenhypophysiotropic neuron might synthesize hormones that are differentboth in chemical nature and physiological function. Furthermore,synthesis of hypophysial hormones could also bedemonstrated in extra-HT cerebral areas and also in nonneuraltissues, in well-defined cell types of different viscera.HT neurons producing hypophysiotropic hormones, besidestheir function as controlling hormone secretion, may act in thecentral nervous system as neurotransmitters or neuromodulators.The neuroanatomical basis of such functions is the intensive projectionof hypophysiotropic neurons to other parts of the endocrineHT and extra-HT structures, such as the limbic system andautonomic nuclei.The activity of the endocrine HT is under the integrated controlof neural inputs to the hypophysiotropic neurons and the feedbackaction of peripheral and hypophysial hormones, exerted either onhypophysiotropic neurons or on extra-HT cerebral structures thatpossess specific hormone receptors. The HT receives informationfrom diverse sources, in order to serve as a main integrator of theendocrine system. The majority of these pathways are reciprocal,i.e., they contain fibers both to and from the HT. The most extensiveconnections of the HT are with limbic structures, such as theamygdala, septum, and hippocampus.The amygdala and the HT (especially the preoptic area andanterior nucleus) are interconnected by the stria terminalis and theventral amygdalofugal bundles. The latter pathway contains fibersalso from the olfactory system. The fornix, originating from thehippocampus, is the largest bundle to the HT. The majority offibers terminate in the mamillary body or originate from it. However,a portion of the fibers, before reaching the column of thefornix, leaves the pathway and terminates in the septal region andin the preoptic area.The well-defined pathway between the HT (mamillary body)and the anterior thalamic nucleus is the mamillothalamic tract.Because the anterior thalamic nucleus is interconnected with thecingulate gyrus, the mamillothalamic tract provides a communicationbetween the HT and the limbic cortex. There is a rich neuralconnection of great functional significance between the HT andbrainstem nuclei, such as the central gray matter, locus ceruleus,other noradrenergic cell groups, raphe nuclei, nucleus of the solitarytract, and reticular formation.Neurons of the paraventricular nucleus send descending fibersalso to the preganglionic sympathetic neurons of thoracolumbarspinal cord segments. There is a direct neural pathway between theretina and the HT suprachiasmatic nucleus. Information from theolfactory system arrives at the HT via limbic structures. However,the HT is not directly linked to the main sensory systems (lemniscuspathways), because of connections of the HT with brainstemnuclei, and thalamic and cortical structures; secondary, tertiarysensory impulses are also conveyed to the HT. Recent studies haverevealed multisynaptic, reciprocal neural connections between theperipheral endocrine glands and the HT.Neural afferents terminating on hypophysiotropic neurons fromseveral brain regions contain different neurotransmitters, aminoacids, and neuropeptides, which may exert a regulatory action onthe synthesis and release of hypophysiotropic hormones. The classicalneurotransmitters, noradrenaline, adrenaline, serotonin, acetylcholine,and γ-amino-butyric acid (GABA), have been provento influence the secretion of HT releasing and inhibiting hormones(see ref. 1).The HT does not contain neurons synthesizing noradrenaline.These neurons are located in different cell groups of the brainstem.The biggest of them is the locus ceruleus. Noradrenergic fibersfrom these cell groups, similar to other ascending bundles, travelin the medial forebrain bundle, then form synaptic contact eitherwith hypophysiotropic neurons or nerve fibers in the median eminence.Noradrenaline plays a significant role in the control of HTneurohormones, such as GnRH or CRH. Adrenaline is also synthesizedin extra-HT cell groups. These neurons are located in thebrainstem. The adrenergic afferents to the HT exert an importantregulatory action on structures involved in the control of GH secretion.The origin of cholinergic fibers innervating hypophysiotropic neuronsis not established. Acetylcholine is an important regulatory factorof CRH, VP, and GHRH/somatostatin secretion.Both the excitatory amino acids (glutamate, aspartate, glycine),and the inhibitory amino acid, GABA, are used by neurons indifferent HT nuclei. The amino acids binding to their receptors onthe hypophysiotropic cells are able to stimulate or inhibit thesecretion of the neurohormones. As mentioned, the HT neuronsalso synthesize several peptide hormones (opioid peptides,vasoactive intestinal peptide (VIP), substance P, galanine, and soon). These peptides and the gaseous neurotransmitter, nitric oxide,can also influence the activity of hypophysiotropic neurons.Besides the rich neural connection of the HT with extra-HTstructures, neuromorphological data have provided evidence forthe existence of the extensive synaptic connections between HTnuclei. These studies have also revealed abundant intranuclearconnections. Furthermore, axon collaterals of a given neurohormone-producingneuron form synaptic contact with the perikaryonwhere the axon originates.BLOOD SUPPLY OF HYPOPHYSIS: PORTAL SYSTEMSecretion of hormones by the adenohypophysis is under thecontrol of the HT by a vascular route (4). Both hypophysial arteries