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hypothalamus

 
Dictionary: hy·po·thal·a·mus   (hī'pō-thăl'ə-məs) pronunciation
n.

The part of the brain that lies below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate bodily temperature, certain metabolic processes, and other autonomic activities.

hypothalamic hy'po·tha·lam'ic (-thə-lăm'ĭk) adj.

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World of the Body: hypothalamus
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Although small, this is one of the most important parts of the grey matter of the brain, for it participates in a number of vital activities. It regulates a variety of hormonal functions by action on the pituitary gland, and it exerts magisterial control over the blood vessels and glands of the body via the autonomic nervous system. It is an integral part of the limbic system, which influences important aspects of our behaviour and even our very survival, regulating such functions as emotion, sexual and nutritional appetites, rhythms, and sleep cycles. Some cells of the hypothalamus detect changes in body temperature and chemistry, and participate directly in the control of our temperature and chemical balance.

The hypothalamus, as its name implies, is situated below the thalamus — a huge collection of nuclei in the centre of the cerebral hemispheres. It forms part of the walls and floor of the central chamber of the cerebral ventricles, called the third ventricle. Hanging on a stalk underneath the hypothalamus is the pituitary gland.

The hypothalamus receives many important sensory inputs, which include information from all the major senses, but especially from the taste and smell receptors and from the viscera. It consists of a number of distinct nerve cell clusters or nuclei. The tiny suprachiasmatic nucleus receives axons directly from the optic nerve, carrying information from the eye, which is used to regulate sleep and other bodily rhythms. This nucleus controls a sympathetic pathway to the pineal gland, which plays its part in the ‘biological clock’ by secreting melatonin in amounts that vary with the time of day. This in turn affects a variety of body processes.

Our internal body clock plays a large part in determining our cycles of sleeping and waking. The connection from the eyes to the suprachiasmatic nucleus is thought to reset the clock each day and hence to keep it locked to the periodicity of the world. If the clock could not be altered (albeit with some difficulty and delay) it would be impossible to adapt to night work or to overcome ‘jet lag’, which afflicts us when we fly to other time zones. Visual input to the hypothalamus also seems to play a part in determining mood. The continuous absence of natural light during the winter months at extreme latitudes can precipitate depression. This condition, which is called Seasonal Affective Disorder, can sometimes be reversed simply by exposing the sufferer to a high-intensity, full-spectrum light for a period of time each day.

Parts of the thalamus, and the frontal lobes of the cerebral cortex that are important in controlling mood, also connect to the hypothalamus. Disturbances in these pathways are thought to result in abnormal affective (emotional) behaviour; some of the symptoms of schizophrenia may be related to this system. Axons of neurons in the hippocampus (a specialized part of the cerebral cortex involved in conscious memory) run in a tract called the fornix, which ends on neurons in the mammillary bodies of the hypothalamus. They then send axons to the thalamus. This circuit, crucially important for linking emotions to events in the outside world, is part of the limbic system.

Many nerve cells in the hypothalamus have a so-called ‘neuroendocrine’ function — instead of producing transmitter substances that simply communicate directly with other neurons, they secrete chemicals that act as hormones, circulating in the blood and affecting other parts of the body. In the front part of the hypothalamus lie the supraoptic and paraventricular nuclei, which send axons down through the stalk of the pituitary gland and into its posterior lobe, called the ‘neurohypophysis’. These nerve fibres end in large swellings that release into the bloodstream the hormones oxytocin (which causes contraction of smooth muscle in the uterus and breast) and vasopression or antidiuretic hormone (which makes blood vessels constrict and controls the salt balance of the body by reducing the loss of water in the urine). The disease diabetes insipidus, in which there is excessive production of urine, is due to damage to the vasopressin system.

Other neuroendocrine parts of the hypothalamus secrete specialized hormones, called ‘releasing factors’, into the blood of small capillary vessels (called the hypophysial portal system), which run down into the anterior lobe of the pituitary gland, where they stimulate specialized cells to secrete other hormones that pass into the general circulation and affect remote organs. These include growth hormone (which regulates growth), prolactin (which controls milk production in the breast), and follicle stimulating hormone (which acts on the ovaries). Two of the hormones of the anterior pituitary act on yet other endocrine glands: adrenocorticotrophic hormone stimulates the adrenal gland and thyrotrophin the thyroid. In these cases, the ‘cascade’ of chemicals (releasing factor, to anterior pituitary hormone, to target endocrine gland) amplifies the effect of the initial signal in the hypothalamus.

The great Oxford neurophysiologist Sir Charles Sherrington called the hypothalamus the ‘head ganglion of the autonomic nervous system’. Anterior parts of the hypothalamus excite parasympathetic functions such as constriction of the pupils of the eye, stimulation of the gastrointestinal tract, salivation, and respiratory and cardiac depression. The posterior hypothalamus brings on sympathetic activity, such as dilatation of the pupils, inhibition of gastrointestinal function and salivation, and increased respiration, heart rate, and blood pressure. These effects are produced by fibres projecting from the hypothalamus to parasympathetic nuclei in the brain stem, and to sympathetic centres in the spinal cord.

— Laurence Garey

See also autonomic nervous system; body clock; brain; thalamus. nervous system.

Dental Dictionary: hypothalamus
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(hī'pō-thal'ə-mus)
n

A small extension of the brain that lies in the sella turcica in the cranium. The hypothalamus lies just at the superior level of the body of the sphenoid bone. It is intimately related structurally and functionally with the pituitary gland and is important in the central regulation of the endocrine glands, including the thyroid gland, pancreas, adrenal glands, and gonads. The most important visceral functions are under control of the hypothalamus because it functions in such close coordination with the endocrine glands. The control is mediated through its structural communication with the pituitary gland.


Region of the brain containing a control centre for many autonomic-nervous-system functions. Its complex interaction with the pituitary gland makes it an important part of the endocrine system. As a critical link between the body's two control systems, the hypothalamus regulates homeostasis. Nervous and hormonal pathways connect it with the pituitary, which it stimulates to release various hormones. The hypothalamus influences food intake, weight regulation, fluid intake and balance, thirst, body heat, and the sleep cycle. Disorders can produce pituitary dysfunction, diabetes insipidus, insomnia, and temperature fluctuations.

For more information on hypothalamus, visit Britannica.com.

Sports Science and Medicine: hypothalamus
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A small portion of the brain derived from the sides and floor of the forebrain. It is the main visceral control centre and is vitally important for homeostasis. It regulates the activity of the autonomic nervous system and a number of endocrine glands. It also contains centres of thermoregulation, ionic regulation, and osmoregulation. The hypothalamus is involved in many other autonomic functions, including the control of thirst, sleep, and hunger. It plays a role in regulating the metabolism of fats, carbohydrates, and proteins, and is also concerned with motivation and emotions.

 
Columbia Encyclopedia: hypothalamus
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hypothalamus (hī'pəthăl'əməs), an important supervisory center in the brain, rich in ganglia, nerve fibers, and synaptic connections. It is composed of several sections called nuclei, each of which controls a specific function. The hypothalamus regulates body temperature, blood pressure, heartbeat, metabolism of fats and carbohydrates, and sugar levels in the blood. Through direct attachment to the pituitary gland, the hypothalamus also meters secretions controlling water balance and milk production in the female. The role of the hypothalamus in awareness of pleasure and pain has been well established in the laboratory. It is thought to be involved in the expression of emotions, such as fear and rage, and in sexual behaviors. Despite its numerous vital functions, the hypothalamus in humans accounts for only 1/300 of total brain weight, and is about the size of an almond. Structurally, it is joined to the thalamus; the two work together to monitor the sleep-wake cycle.


Health Dictionary: hypothalamus
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(heye-puh-thal-uh-muhs)

The part of the brain that controls hunger, thirst, and body temperature and regulates various activities in the body connected with metabolism, including the maintaining of water balance. The hypothalamus also controls the action of the pituitary gland.

Veterinary Dictionary: hypothalamic
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Pertaining to the hypothalamus.

  • h. hormones — see hypothalamus.
  • h.–pituitary–adrenocortical axis — the complex system of interaction between the hypothalamus, pituitary gland and adrenal cortex that involves stimulation of synthesis and release by corticotropin-releasing factor and adrenocorticotropic hormone, and the negative feedback effect of cortisol.
  • h. secretory neurons — are located in nuclei of the hypothalmus; they receive information from higher centers to regulate hormone secretion.
  • h. thermoregulatory mechanism — receptive to stimulation by pyrogens to elevate the body temperature in fever.
Wikipedia: Hypothalamus
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Brain: Hypothalamus
LocationOfHypothalamus.jpg
Location of the human hypothalamus
Illu diencephalon .jpg
Diencephalon
Latin hypothalamus
Gray's subject #189 812
NeuroNames hier-358
MeSH Hypothalamus
NeuroLex ID birnlex_734

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland (hypophysis).

The hypothalamus is located below the thalamus, just above the brain stem. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is roughly the size of an almond.

The hypothalamus is responsible for certain metabolic processes and other activities of the Autonomic Nervous System. It synthesizes and secretes neurohormones, often called hypothalamic-releasing hormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. The hypothalamus controls body temperature, hunger, thirst,[1] fatigue, and circadian cycles.

Contents

Inputs

Hypothalamus (Animation)

The hypothalamus is a complex region in the brain of humans, and even small nuclei within the hypothalamus are involved in many different functions. The paraventricular nucleus for instance contains oxytocin and vasopressin (also called antidiuretic hormone) neurons which project to the posterior pituitary, but also contains neurons that regulate ACTH and TSH secretion (which project to the anterior pituitary), gastric reflexes, maternal behavior, blood pressure, feeding, immune responses, and temperature.

The hypothalamus co-ordinates many hormonal and behavioural circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms,[2] and many important behaviours.

The hypothalamus must therefore respond to many different signals, some of which are generated externally and some internally. It is thus richly connected with many parts of the central nervous system, including the brainstem reticular formation and autonomic zones, the limbic forebrain (particularly the amygdala, septum, diagonal band of Broca, and the olfactory bulbs, and the cerebral cortex).

The hypothalamus is responsive to:

  • Light: daylength and photoperiod for regulating circadian and seasonal rhythms
  • Olfactory stimuli, including pheromones
  • Steroids, including gonadal steroids and corticosteroids
  • Neurally transmitted information arising in particular from the heart, the stomach, and the reproductive tract
  • Autonomic inputs
  • Blood-borne stimuli, including leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines, plasma concentrations of glucose and osmolarity etc
  • Stress
  • Invading microorganisms by increasing body temperature, resetting the body's thermostat upward.

Olfactory stimuli

Olfactory stimuli are important for sex and neuroendocrine function in many species. For instance if a pregnant mouse is exposed to the urine of a 'strange' male during a critical period after coitus then the pregnancy fails (the Bruce effect). Thus during coitus, a female mouse forms a precise 'olfactory memory' of her partner which persists for several days. Pheromonal cues aid synchronisation of oestrus in many species; in women, synchronised menstruation may also arise from pheromonal cues, although the role of pheromones in humans is doubted by many.

Blood-borne stimuli

Peptide hormones have important influences upon the hypothalamus, and to do so they must evade the blood-brain barrier. The hypothalamus is bounded in part by specialized brain regions that lack an effective blood-brain barrier; the capillary endothelium at these sites is fenestrated to allow free passage of even large proteins and other molecules. Some of these sites are the sites of neurosecretion - the neurohypophysis and the median eminence. However others are sites at which the brain samples the composition of the blood. Two of these sites, the subfornical organ and the OVLT (organum vasculosum of the lamina terminalis) are so-called circumventricular organs, where neurons are in intimate contact with both blood and CSF. These structures are densely vascularized, and contain osmoreceptive and sodium-receptive neurons which control drinking, vasopressin release, sodium excretion, and sodium appetite. They also contain neurons with receptors for angiotensin, atrial natriuretic factor, endothelin and relaxin, each of which is important in the regulation of fluid and electrolyte balance. Neurons in the OVLT and SFO project to the supraoptic nucleus and paraventricular nucleus, and also to preoptic hypothalamic areas. The circumventricular organs may also be the site of action of interleukins to elicit both fever and ACTH secretion, via effects on paraventricular neurons.

It is not clear how all peptides that influence hypothalamic activity gain the necessary access. In the case of prolactin and leptin, there is evidence of active uptake at the choroid plexus from blood into CSF. Some pituitary hormones have a negative feedback influence upon hypothalamic secretion; for example, growth hormone feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of prolactin and TSH.

The hypothalamus functions as a type of thermostat for the body.[3] It sets a desired body temperature, and stimulates either heat production and retention to raise the blood temperature to a higher setting, or sweating and vasodilation to cool the blood to a lower temperature. All fevers result from a raised setting in the hypothalamus; elevated body temperatures due to any other cause are classified as hyperthermia.[3] Rarely, direct damage to the hypothalamus, such as from a stroke, will cause a fever; this is sometimes called a hypothalamic fever. However, it is more common for such damage to cause abnormally low body temperatures.[3]

Steroids

The hypothalamus contains neurons that react strongly to steroids and glucocorticoids – (the steroid hormones of the adrenal gland, released in response to ACTH). It also contains specialised glucose-sensitive neurons (in the arcuate nucleus and ventromedial hypothalamus), which are important for appetite. The preoptic area contains thermosensitive neurons; these are important for TRH secretion.

Neural inputs

The hypothalamus receives many inputs from the brainstem; notably from the nucleus of the solitary tract, the locus coeruleus, and the ventrolateral medulla. Oxytocin secretion in response to suckling or vagino-cervical stimulation is mediated by some of these pathways; vasopressin secretion in response to cardiovascular stimuli arising from chemoreceptors in the carotid sinus and aortic arch, and from low-pressure atrial volume receptors, is mediated by others. In the rat, stimulation of the vagina also causes prolactin secretion, and this results in pseudo-pregnancy following an infertile mating. In the rabbit, coitus elicits reflex ovulation. In the sheep, cervical stimulation in the presence of high levels of estrogen can induce maternal behavior in a virgin ewe. These effects are all mediated by the hypothalamus, and the information is carried mainly by spinal pathways that relay in the brainstem. Stimulation of the nipples stimulates release of oxytocin and prolactin and suppresses the release of LH and FSH.

Cardiovascular stimuli are carried by the vagus nerve, but the vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension to suppress feeding. Again this information reaches the hypothalamus via relays in the brainstem.

Nuclei

A cross section of the monkey hypothalamus displays 2 of the major hypothalamic nuclei on either side of the fluid-filled 3rd ventricle

Hypothalamic nuclei

The hypothalamic nuclei include the following:[4][5][6]

Hypothalamic nuclei
Region Area Nucleus Function[7]
Anterior Medial Medial preoptic nucleus
Supraoptic nucleus (SO)
Paraventricular nucleus (PV)
Anterior hypothalamic nucleus (AH)
Suprachiasmatic nucleus (SC)
Lateral Lateral preoptic nucleus
Lateral nucleus (LT)
Part of supraoptic nucleus (SO)
Tuberal Medial Dorsomedial hypothalamic nucleus (DM)
  • GI stimulation
Ventromedial nucleus (VM)
Arcuate nucleus (AR)
  • Lutenizing Hormone R.H. release
  • Follicle Stimulating Hormone Releasing Factor
  • feeding
  • Dopamine
  • GHRH
Lateral Lateral nucleus (LT)
Lateral tuberal nuclei
Posterior Medial Mammillary nuclei (part of mammillary bodies) (MB)
Posterior nucleus (PN)
Lateral Lateral nucleus (LT)
See also: ventrolateral preoptic nucleus

Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction

Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction

Outputs

The outputs of the hypothalamus can be divided into two categories: neural projections, and endocrine hormones.[9]

Neural projections

Most fiber systems of the hypothalamus run in two ways (bidirectional).

Endocrine hormones

The Hypothalamus affects the endocrine system and governs emotional behavior, such as, anger and sexual activity. Most of the hypothalamic hormones generated are distributed to the pituitary via the hypophyseal portal system.[10] The hypothalamus maintains homeostasis this includes a regulation of blood pressure, heart rate, and temperature.

Secreted hormone Abbreviation Produced by Effect
Thyrotropin-releasing hormone
(Prolactin-releasing hormone)
TRH, TRF, or PRH Parvocellular neurosecretory neurons Stimulate thyroid-stimulating hormone (TSH) release from anterior pituitary (primarily)
Stimulate prolactin release from anterior pituitary
Dopamine
(Prolactin-inhibiting hormone)
DA or PIH Dopamine neurons of the arcuate nucleus Inhibit prolactin release from anterior pituitary
Growth hormone-releasing hormone GHRH Neuroendocrine neurons of the Arcuate nucleus Stimulate Growth hormone (GH) release from anterior pituitary
Somatostatin
(growth hormone-inhibiting hormone)
SS, GHIH, or SRIF Neuroendocrine cells of the Periventricular nucleus Inhibit Growth hormone (GH) release from anterior pituitary
Inhibit thyroid-stimulating hormone (TSH) release from anterior pituitary
Gonadotropin-releasing hormone GnRH or LHRH Neuroendocrine cells of the Preoptic area Stimulate follicle-stimulating hormone (FSH) release from anterior pituitary
Stimulate luteinizing hormone (LH) release from anterior pituitary
Corticotropin-releasing hormone CRH or CRF Parvocellular neurosecretory neurons Stimulate adrenocorticotropic hormone (ACTH) release from anterior pituitary
Oxytocin Magnocellular neurosecretory cells Uterine contraction
Lactation (letdown reflex)
Vasopressin
(antidiuretic hormone)
ADH or AVP Parvocellular neurosecretory neurons Increases water permeability in the distal convoluted tubule and collecting duct of nephrons, thus promoting water reabsorption and increasing blood volume

See also: Hypocretin

Control of food intake

The extreme lateral part of the ventromedial nucleus of the hypothalamus is responsible for the control of food intake. Stimulation of this area causes increased food intake. Bilateral lesion of this area causes complete cessation of food intake. Medial parts of the nucleus have a controlling effect on the lateral part. Bilateral lesion of the medial part of the ventromedial nucleus causes hyperphagia and obesity of the animal. Further lesion of the lateral part of the ventromedial nucleus in the same animal produces complete cessation of food intake.

There are different hypotheses related to this regulation:[11]

  1. Lipostatic hypothesis - this hypothesis holds that adipose tissue produces a humoral signal that is proportionate to the amount of fat and acts on the hypothalamus to decrease food intake and increase energy output. It has been evident that a hormone leptin acts on the hypothalamus to decrease food intake and increase energy output.
  2. Gutpeptide hypothesis - gastrointestinal hormones like Grp, glucagons, CCK and others claimed to inhibit food intake. The food entering the gastrointestinal tract triggers the release of these hormones which acts on the brain to produce satiety. The brain contains both CCK-A and CCK-B receptors.
  3. Glucostatic hypothesis - the activity of the satiety center in the ventromedial nuclei is probably governed by the glucose utilization in the neurons. It has been postulated that when their glucose utilization is low and consequently when the arteriovenous blood glucose difference across them is low, the activity across the neurons decrease. Under these conditions, the activity of the feeding center is unchecked and the individual feels hungry. Food intake is rapidly increased by intraventricular administration of 2-deoxyglucose therefore decreasing glucose utilization in cells.
  4. Thermostatic hypothesis - according to this hypothesis, a decrease in body temperature below a given set point stimulates appetite, while an increase above the set point inhibits appetite.

Sexual dimorphism

Several hypothalamic nuclei are sexually dimorphic, i.e. there are clear differences in both structure and function between males and females.

Some differences are apparent even in gross neuroanatomy: most notable is the sexually dimorphic nucleus within the preoptic area, which is present only in males. However most of the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons.

The importance of these changes can be recognised by functional differences between males and females. For instance, males of most species prefer the odor and appearance of females over males, which is instrumental in stimulating male sexual behavior. If the sexually dimorphic nucleus is lesioned, this preference for females by males diminishes. Also, the pattern of secretion of growth hormone is sexually dimorphic, and this is one reason why in many species, adult males are much larger than females.

Responses to ovarian steroids

Other striking functional dimorphisms are in the behavioral responses to ovarian steroids of the adult. Males and females respond differently to ovarian steroids, partly because the expression of estrogen-sensitive neurons in the hypothalamus is sexually dimorphic, i.e. estrogen receptors are expressed in different sets of neurons.

Estrogen and progesterone can influence gene expression in particular neurons or induce changes in cell membrane potential and kinase activation, leading to diverse non-genomic cellular functions. Estrogen and progesterone bind to their cognate nuclear hormone receptors, which translocate to the cell nucleus and interact with regions of DNA known as hormone response elements (HREs) or get tethered to another transcription factor's binding site. Estrogen receptor (ER) has been shown to transactivate other transcription factors in this manner, despite the absence of an estrogen response element (ERE) in the proximal promoter region of the gene. ERs and progesterone receptors (PRs) are generally gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.

Male and female brains differ in the distribution of estrogen receptors, and this difference is an irreversible consequence of neonatal steroid exposure. Estrogen receptors (and progesterone receptors) are found mainly in neurons in the anterior and mediobasal hypothalamus, notably:

Gonadal steroids in neonatal life of rats

In neonatal life, gonadal steroids influence the development of the neuroendocrine hypothalamus. For instance, they determine the ability of females to exhibit a normal reproductive cycle, and of males and females to display appropriate reproductive behaviors in adult life.

  • If a female rat is injected once with testosterone in the first few days of postnatal life (during the "critical period" of sex-steroid influence), the hypothalamus is irreversibly masculinized; the adult rat will be incapable of generating an LH surge in response to estrogen (a characteristic of females), but will be capable of exhibiting male sexual behaviors (mounting a sexually receptive female).
  • By contrast, a male rat castrated just after birth will be feminized, and the adult will show female sexual behavior in response to estrogen (sexual receptivity, lordosis behavior).

Androgens in primates

In primates, the developmental influence of androgens is less clear, and the consequences are less complete. 'Tomboyism' in girls might reflect the effects of androgens on the fetal brain, but the sex a child is reared as during the first 2–3 years is believed by many to be the most important determinant of gender identity, because during this phase either estrogen or testosterone will have permanent effects on either a female or male brain, influencing both heterosexuality and homosexuality.[12]

The paradox is that the masculinizing effects of testosterone are mediated by estrogen. Within the brain, testosterone is aromatized to (estradiol), which is the principal active hormone for developmental influences. The human testis secretes high levels of testosterone from about week 8 of fetal life until 5–6 months after birth (a similar perinatal surge in testosterone is observed in many species), a process that appears to underlie the male phenotype. Estrogen from the maternal circulation is relatively ineffective, partly because of the high circulating levels of steroid-binding proteins in pregnancy.

Other influences upon hypothalamic development

Sex steroids are not the only important influences upon hypothalamic development; in particular, pre-pubertal stress in early life determines the capacity of the adult hypothalamus to respond to an acute stressor.[13] Unlike gonadal steroid receptors, glucocorticoid receptors are very widespread throughout the brain; in the paraventricular nucleus, they mediate negative feedback control of CRF synthesis and secretion, but elsewhere their role is not well understood.

See also

Additional images

References

  1. ^ Definition of hypothalamus - NCI Dictionary of Cancer Terms
  2. ^ hypothalamus
  3. ^ a b c Fauci, Anthony, et al. (2008). Harrison's Principles of Internal Medicine (17 ed.). McGraw-Hill Professional. ISBN 9780071466332. 
  4. ^ Diagram of Nuclei (psycheducation.org)
  5. ^ Diagram of Nuclei (universe-review.ca)
  6. ^ Diagram of Nuclei (utdallas.edu)
  7. ^ Unless else specified in table, then ref is: Guyton Eight Edition
  8. ^ Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3.  Page 840
  9. ^ Hypothalamus and ANS
  10. ^ Overview of Hypothalamic and Pituitary Hormones
  11. ^ Theologides A (1976). "Anorexia-producing intermediary metabolites". Am J Clin Nutr 29 (5): 552–8. PMID 178168. 
  12. ^ John Money, 'The concept of gender identity disorder in childhood and adolescence after 39 years', Journal of Sex and Marital Therapy 20 (1994): 163-77.
  13. ^ Romeo, Russell D; Rudy Bellani, Ilia N. Karatsoreos, Nara Chhua, Mary Vernov, Cheryl D. Conrad and Bruce S. McEwen (2005). "Stress History and Pubertal Development Interact to Shape Hypothalamic-Pituitary-Adrenal Axis Plasticity". Endocrinology (The Endocrine Society) 147 (4): 1664–1674. doi:10.1210/en.2005-1432. PMID 16410296. http://endo.endojournals.org/cgi/content/short/147/4/1664. Retrieved 2007-10-16. 

Added Reference

de Vries, GJ, and Sodersten P (2009) Sex differences in the brain: the relation between structure and function. Hormones and Behavior 55:589-596.

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