What makes up the hypothalamus

Inferior surface of the brain with hypothalamic visualization at this level. The pituitary gland is a three-lobe structure: anterior, posterior and intermediate lobe, with different embryological origin. The anterior gland contains a heterogeneous cellularity that synthesized and secreted hormones in the blood stream: the majority of the cells are somatotrope cells that produced the human growth hormone hGH or somatotropin hormone STH , a peptide that promotes growth in childhood.

The production of the somatotropic hormone is under the control of the hypothalamic growth-releasing hormone GRH produced by the arcuate nucleus. The next hormones produced in high quantity by the anterior gland of the hypophysis are the corticotrope ones adrenocorticotropic hormone—ACTH, melanocyte-stimulating hormone—MSH, and beta-endorphins. This group of hormones is under the control of the hypothalamic corticotropin-relasing hormones CRHs derived from the paraventricular nuclei.

In smaller percentages, the adenohypophysis has population of cells that produced thyrotropes, gonadotropes, and lactotropes. Thyrotropes respond to signals from the hypothalamic thyrotropin-releasing hormone TRH produced in the paraventricular nuclei and further synthesize the hormone responsible for thyroid hormones production—thyroid stimulating hormone TSH.

Luteinizing hormones LHs and follicle stimulating hormones FSHs are secreted by gonadotrope cells of the gland under the influence of pulsatile secretion of gonadotropin-releasing hormone GRH produced in hypothalamus preoptic area. The secretion of prolactine PRL from the lactotropes is stimulated by hypothalamic thyrotropin-releasing hormone TRH and inhibited by the dopamine [ 9 ].

Hypothalamic hormones reach the adenohypophysis through a vascular system. Hypothalamus exerts its effects over the anterior part of the gland through the hypothalamo-hypophyseal portal system, a special vascular system formed by fenestrated capillaries.

The proximal vascular structure of the portal system is the anterior hypophyseal artery, branch from the ophthalmic segment of the internal carotid artery [ 9 ]. Through it, hypothalamic hormones are transported to the primary plexus, located near the infundibulum of the hypothalamus. From this region, hormones are drained into the second vascular venous plexus of the hypothalamo-hypophyseal portal system that surrounds the adenohypophysis [ 9 ].

This vascular system allows hormones to diffuse through the wall, inside of the gland. The hypophyseal vein further drains the blood into the venous sinuses of the dura mater and from here in the venous system of the body. It is absent or of small size in adults. The posterior lobe of the gland, pars distalis or neurohypophysis derives from the neuroectoderm [ 9 ]. It is an inferior extension of the hypothalamus and is mainly from its neural fibers.

The connection between the hypothalamus and the posterior lobe of the gland forms the infundibular stalk. Through this complex, hormones synthetized in the hypothalamus nuclei are transported and deposited in the posterior gland where they are stored in presynaptic vesicles and then released into the blood stream.

The supraoptic nuclei of the hypothalamus are responsible for the secretion of antiduretic hormone ADH or vasopressin, the hormone involved in maintaining the water balance in organism and thus in preventing dehydration. The paraventricular nuclei produce oxytocin, a hormone released during labor, in the presence of uterine contractions. The hypothalamus intervenes along with the pituitary gland the majority of the endocrine and metabolic functions of the body through a double-sense transport of hormones between the two structures.

The hypothalamus is divided by the anterior horns of the fornix in a lateral, medial, and periventricular median region and by a coronal plane passing through the infundibulum in an anterior and posterior region.

The anterior region is also referred to as the prechiasmatic region, due to its location above the chiasma optic, while the posterior region is called the mammillary region. The infundibular region is situated between the previous two regions. From a structural point of view, the hypothalamus is formed by gray matter conglomeration of neurons that organize in nuclei and also by white-matter substance formed by myelinated nervous fibers.

The anterior region of the hypothalamus is located above the optic chiasm and is referred to as the supraoptic area. It contains the following nucleus: supraoptic, preoptic and medial preoptic, the suprachiasmatic and the anterior hypothalamic nucleus, alongside with the paraventricular one Figure 2. The supraoptic nucleus produces vasopressin or the antidiuretic hormone ADH that is stored in the posterior lobe of the pituitary gland and is responsible for blood pressure control and water balance of the organism.

The preoptic region alongside with the anterior hypothalamic nucleus is involved in cooling thermoregulation of the body through the sweating process. The preoptic nucleus is also involved in the habit of eating and in reproduction while the medial preoptic region is involved in cardiovascular control as a response to stress [ 10 ]. The suprachiasmatic nucleus is situated above the optic chiasm and is involved in the circadian rhythm.

The paraventricular nucleus named after its location near the third diencephalic ventricle represents an important autonomic center of the brain involved in stress and metabolism control [ 11 ]. Schematic representation of hypothalamic nuclei sagittal section. The central part as the hypothalamus is located above tuber cinereum and is named the tuberal area.

It is composed of two parts, anterior and lateral, and contains the following nucleus: dorsomedial, ventromedial, paraventricular, supraoptic, and arcuate Figure 2. The ventromedial area is involved in controlling the habits of eating and the feeling of satiety [ 12 ]. The arcuate or infundibular nucleus is responsible for orexigenic peptides secretion: ghrelin, orexin, or neuropeptide Y [ 11 ].

The posterior region is formed by a medial and, respectively, lateral area. The medial region contains the mammillary nucleus alongside with the posterior hypothalamic nucleus, the supramammillary and the tuberomammillary ones.

The nucleus of the lateral region contains the hypocretins orexin peptides that control feeding behavior, thermoregulation, gastrointestinal motility [ 13 ], and cardiovascular regulation and are also involved in sleep regulation [ 14 ]. Lesions of the lateral region lead to the refusal to feed or aphagia.

The posterior part of the hypothalamus is involved overall in energy balance, blood pressure, memory, and learning. The posterior hypothalamic nucleus has a major role in controlling the body temperature [ 12 ]. The tuberomammillar nucleus is involved in memory due to their connection with the hippocampus and Papez memory circuit [ 9 ]. The hypothalamus is a small region of the brain connected with numerous, various cerebral structures that allows it to intervene in many regulatory processes of the organism.

More, the hypothalamus is involved in the homeostasis of the organism in terms of body temperature, blood pressure, fluid balance, and body weight. The ascending reticular activating system represents a structure composed by neural fibers passing from the reticular formation of the midbrain, through the thalamus, reaching the cerebral cortex [ 15 ].

The system is responsible for concentration, attention, and for maintaining the awakening state. Through it, the reticular formation is connected with the hypothalamic nuclei: the lateral mammillary bodies [ 12 ], the tuberomammillar nuclei, and the periventricular ones. The periventricular nuclei receive information about the general visceral sensibility [ 16 ] while the two others mediate behavior and are involved in consciousness [ 17 ].

These pathways include the hypophyseal-portal system of blood vessels that surround the median eminence, the infundibulum and pituitary gland. The details of this system in neuroendocrine function will comprise the third chapter of this section. Circumventricular Organs.

There are several sites at which the blood brain barrier is highly permeable and at which specific transporters are present that allow passage of chemosensory stimuli from the blood into the brain. For example, the organum vasculosum of the lamina terminalis is the site at which pyrogens such as interleukin-1 and tumor necrosis factor bind to receptors that transport these molecules into the CNS and initiate the central synthesis of prostaglandins.

These in turn act on the anterior nucleus to initiate a change in body temperature set-point resulting in fever. Passage of hormones through both the organum vasculosum and the median eminence is essential for normal feedback on the hypothalamus for neuroendocrine control.

The area postrema is the location of the chemotoxic trigger zone at which emesis is induced by various toxins in the blood stream and that affect the hypothalamus to induce taste aversion. Passage of peptides through the subfornical organ are thought to participate in mechanisms of learning, while passage of signals through the pineal body affects circadian and circannual timing patterns.

It has been highlighted several times in this section that the overarching function of the hypothalamus is the integration of body functions for the maintenance of homeostasis.

The multiplicity of functions that are entailed in this level of integration should be intuitively obvious. The table below lists many of these functions and the nuclear groups that are most closely associated their execution. Thermoregulation, Neuroendocrine control, Feeding and Satiety.

The details concerning thermoregulation, neuroendocrine function, and control of feeding will be the subject of later chapters. Biological Timing and Rhythms. Circadian timing refers to the daily fluctuations that occur in hormone levels, body temperature, sleep-wake cycle, etc. The neurons in the SCN have an intrinsic rhythm of discharge activity that will re-cycle in the absence of light at 25 hour intervals. This activity is an intrinsic property of SCN neurons that can be maintained for days while the cells are maintained in culture.

Input to the SCN from the retinohypothalamic tract resets and entrains the activity of SCN neurons to the daily 24 hour light-dark cycle by regulating the transcription of the light-sensitive clock , bmal , period per and cryptochrome cry genes. The retino-hypothalamic tract is a non-rod, non-cone dependent input to the SCN from a subset of retinal ganglion cells that are directly activated by light interacting with the pigment melanopsin.

The SCN has projections into multiple hypothalamic nuclei that control the specific functions that show daily or annual rhythms.

Thus, the SCN is considered as a master pacemaker that regulates the functions of multiple intra- and extra-hypothalamic slave oscillators. One extraordinary example of an extra-hypothalamic slave oscillator is the induction of fetal circadian timing from the mother. A specific, and perhaps more concrete example of this circuitry is illustrated by the regulation of melatonin secretion.

Activation of the SCN by light results in increased input to the paraventricular nucleus, which in turn activates sympathetic pre-ganglionic neurons in the T1-T2 spinal intermediolateral cell column. These neurons inhibit the superior cervical ganglion which sends noradrenergic innervation into the pineal gland that inhibits the release of melatonin. With the onset of darkness, this inhibition is removed, and so melatonin secretion increases through a disinhibition process Figure 1.

There are two major classes of disorders in circadian timing, phase shifting and entrainment failure, both of which manifest themselves as sleep disorders. The most common phase shift disorder is the rapid time-zone change syndrome, or jet lag, characterized by daytime sleepiness and nighttime insomnia. The molecular biology of this disorder is becoming well-defined.

Circadian disruption is more sensitive to advances in local time than to delays. It is only when the expression of both genes resume their baseline parallel expression that the behavioral and light:dark cycles become re-aligned. In contrast, mPer and mCry expression cycles react rapidly and in parallel with a delay in light cycle, such that a complete reset is achieved within one cycle.

A second type of phase shift disorder is delayed sleep phase syndrome commonly seen in adolescents and possibly linked to an endocrine-mediated desensitization of SCN pacemakers to phase-advancing stimuli. Finally, advanced sleep phase syndrome, characterized by onset of sleep in the early evening followed by very early pre-dawn awakening is commonly observed in the elderly and is associated with a missense mutation in mPer2. Entrainment failure is often, though not always, observed in the blind.

It is important to remember that the retino-hypothalamic tract has nothing to do with vision and so can be preserved in the blind, and may also be absent in those with vision. It has become increasingly evident that circadian timing can have tremendous impact on the susceptibility to disease as well as conversely, to the optimal timing of curative therapy Figure 1.

Chronomorbidity refers to the observation that certain disorders characteristically show peak prevalence at particular times of the day, whereas Chronotherapeutics is the application of therapies at the time of day when their effects can be expected to have the greatest impact. The best current example of effective chronotherapeutics is that treatment of seasonal affective disorder a form of entrainment failure is successfully treated with bright light therapy only when applied during the morning hours.

The hypothalamus is the key brain site for integration of multiple biologic systems to maintain homeostasis. Neurons in the hypothalamus discharge in relation to multiple physiologic indices and change discharge rate with changes in these indices, thus establishing set points. The three major systems controlled by the hypothalamus for maintenance of homeostasis are the autonomic nervous system, the neuroendocrine system, and the limbic system.

The hypothalamus has well defined anatomical boundaries. Different regions of the hypothalamus are especially associated with the control of specific physiological subsystems. The broad scope of brain regions affected by the hypothalamus is reflected by a very widespread extent of connectivity of the hypothalamus to other brain areas and by unique neuro-humoral communication pathways.

One key function of the hypothalamus is regulation of body functions in concert with the daily light:dark cycle.

Intrinsic timing mechanisms of neurons in the suprachiasmatic nucleus controlled by the expression of the light sensitive clock , bmal , per , and cry genes establish the master pacemaker of the body. The activity of these cells is set in phase to light by inputs from a special subset of non-rod, non-cone dependent melanopsin-containing retinal ganglion cells via the retino-hypothalamic tract.

The medial forebrain bundle. Which of the following characteristics best accounts for the hypothalamus being the key brain region for control of homeostasis? The hypothalamus is the only brain region that both sends and receives information to the body via the blood stream.

There are two sets of nerve cells in the hypothalamus that produce hormones. One set sends the hormones they produce down through the pituitary stalk to the posterior lobe of the pituitary gland where these hormones are released directly into the bloodstream. These hormones are anti-diuretic hormone and oxytocin.

Anti-diuretic hormone causes water reabsorption at the kidneys and oxytocin stimulates contraction of the uterus in childbirth and is important in breastfeeding. The other set of nerve cells produces stimulating and inhibiting hormones that reach the anterior lobe of the pituitary gland via a network of blood vessels that run down through the pituitary stalk. The hormones produced in the hypothalamus are corticotrophin-releasing hormone , dopamine, growth hormone-releasing hormone , somatostatin , gonadotrophin-releasing hormone and thyrotrophin-releasing hormone.

Hypothalamic function can be affected by head trauma, brain tumours, infection, surgery, radiation and significant weight loss. It can lead to disorders of energy balance and thermoregulation, disorganised body rhythms, insomnia and symptoms of pituitary deficiency due to loss of hypothalamic control. Pituitary deficiency hypopituitarism ultimately causes a deficiency of hormones produced by the gonads, adrenal cortex and thyroid gland, as well as loss of growth hormone.

Lack of anti-diuretic hormone production by the hypothalamus causes diabetes insipidus.