Hypothalamus

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Hypothalamus
Location of the human hypothalamus
Location of the hypothalamus (cyan) in relation to the pituitary and to the rest of the brain
Details
Part ofBrain
Identifiers
Latinhypothalamus
MeSHD007031
NeuroLex IDbirnlex_734
TA98A14.1.08.401
A14.1.08.901
TA25714
FMA62008
Anatomical terms of neuroanatomy
Not to be confused with Subthalamus.

The hypothalamus (pl.: hypothalami; from

ventral part of the diencephalon. All vertebrate brains contain a hypothalamus.[2] In humans, it is the size of an almond.[citation needed
]

The hypothalamus is responsible for regulating certain

fatigue, sleep, circadian rhythms, and is important in certain social behaviors, such as sexual and aggressive behaviors.[4][5]

Structure

The hypothalamus is divided into four regions (preoptic, supraoptic, tuberal, mammillary) in a parasagittal plane, indicating location anterior-posterior; and three zones (periventricular, intermediate, lateral) in the coronal plane, indicating location medial-lateral.

paraventricular nucleus and the supraoptic nucleus of the hypothalamus produce neurohypophysial hormones, oxytocin and vasopressin.[8] These hormones are released into the blood in the posterior pituitary.[9] Much smaller parvocellular neurosecretory cells, neurons of the paraventricular nucleus, release corticotropin-releasing hormone and other hormones into the hypophyseal portal system, where these hormones diffuse to the anterior pituitary.[citation needed
]

Nuclei

The hypothalamic nuclei include the following:[10][11]

List of nuclei, their functions, and the neurotransmitters, neuropeptides, or hormones that they utilize
Region Area Nucleus Function[12]
Anterior (supraoptic) Preoptic Preoptic nucleus
Medial
Medial preoptic nucleus
  • Regulates the release of gonadotropic hormones from the adenohypophysis
  • Contains the sexually dimorphic nucleus, which releases GnRH, differential development between sexes is based upon in utero testosterone levels
  • Thermoregulation[13]
Supraoptic nucleus
Paraventricular nucleus
Anterior hypothalamic nucleus
Suprachiasmatic nucleus
  • Circadian rhythms
Lateral
Lateral nucleus
 See Lateral hypothalamus § Function – primary source of orexin neurons that project throughout the brain and spinal cord
Middle (tuberal) Medial Dorsomedial hypothalamic nucleus
Ventromedial nucleus
Arcuate nucleus
  • Growth hormone-releasing hormone
    (GHRH)
  • feeding
  • Dopamine-mediated prolactin inhibition
Lateral
Lateral nucleus
 See Lateral hypothalamus § Function – primary source of orexin neurons that project throughout the brain and spinal cord
Lateral tuberal nuclei
Posterior (mammillary) Medial Mammillary nuclei (part of mammillary bodies)
Posterior nucleus
Lateral
Lateral nucleus
 See Lateral hypothalamus § Function – primary source of orexin neurons that project throughout the brain and spinal cord
Tuberomammillary nucleus[14]
  • arousal (wakefulness and attention)
  • feeding and
    energy balance
  • learning
  • memory
  • sleep
  • Cross-section of the monkey hypothalamus displays two of the major hypothalamic nuclei on either side of the fluid-filled third ventricle.
    Cross-section of the monkey hypothalamus displays two of the major hypothalamic nuclei on either side of the fluid-filled third ventricle.
  • Hypothalamic nuclei
    Hypothalamic nuclei
  • Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction[15]
    Hypothalamic nuclei on one side of the hypothalamus, shown in a 3-D computer reconstruction[15]

Connections

Further information: Lateral hypothalamus § Orexinergic projection system, and Tuberomammillary nucleus § Histaminergic outputs

The hypothalamus is highly interconnected with other parts of the

autonomous nervous system
.

The hypothalamus receives many inputs from the

nucleus of the solitary tract, the locus coeruleus, and the ventrolateral medulla
.

Most nerve fibres within the hypothalamus run in two ways (bidirectional).

Sexual dimorphism

Several hypothalamic nuclei are

sexually dimorphic; i.e., there are clear differences in both structure and function between males and females.[16] Some differences are apparent even in gross neuroanatomy: most notable is the sexually dimorphic nucleus within the preoptic area,[16] in which the differences are subtle changes in the connectivity and chemical sensitivity of particular sets of neurons. The importance of these changes can be recognized 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;[17]
this is why in many species, adult males are visibly distinct sizes from females.

Responsiveness to ovarian steroids

Other striking functional dimorphisms are in the behavioral responses to

ovarian steroids of the adult. Males and females respond to ovarian steroids in different ways, 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.[citation needed
]

estrogen response element (ERE) in the proximal promoter region of the gene. In general, ERs and progesterone receptors (PRs) are gene activators, with increased mRNA and subsequent protein synthesis following hormone exposure.[citation needed
]

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

  • the
    LHRH neurons are located, regulating dopamine responses and maternal behavior;[18]
  • the periventricular nucleus where somatostatin neurons are located, regulating stress levels;[19]
  • the
    ventromedial hypothalamus
    which regulates hunger and sexual arousal.

Development

Median sagittal section of brain of human embryo of three months

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.

In primates, the developmental influence of

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.[20]

paraventricular nucleus, they mediate negative feedback control of CRF
synthesis and secretion, but elsewhere their role is not well understood.

Function

Hormone release

Endocrine glands in the human head and neck and their hormones

The hypothalamus has a central

axons to either the median eminence or the posterior pituitary, where they are stored and released as needed.[22]

Anterior pituitary

In the hypothalamic–adenohypophyseal axis, releasing hormones, also known as hypophysiotropic or hypothalamic hormones, are released from the median eminence, a prolongation of the hypothalamus, into the hypophyseal portal system, which carries them to the anterior pituitary where they exert their regulatory functions on the secretion of adenohypophyseal hormones.[23] These hypophysiotropic hormones are stimulated by parvocellular neurosecretory cells located in the periventricular area of the hypothalamus. After their release into the capillaries of the third ventricle, the hypophysiotropic hormones travel through what is known as the hypothalamo-pituitary portal circulation. Once they reach their destination in the anterior pituitary, these hormones bind to specific receptors located on the surface of pituitary cells. Depending on which cells are activated through this binding, the pituitary will either begin secreting or stop secreting hormones into the rest of the bloodstream.[24]

Secreted hormone Abbreviation Produced by Effect
Thyrotropin-releasing hormone
(Prolactin-releasing hormone) 		TRH, TRF, or PRH
paraventricular nucleus
 Stimulate thyroid-stimulating hormone (TSH) release from anterior pituitary (primarily)
Stimulate prolactin release from anterior pituitary
Corticotropin-releasing hormone CRH or CRF Parvocellular neurosecretory cells of the paraventricular nucleus Stimulate adrenocorticotropic hormone (ACTH) 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
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
Somatostatin[25]
(growth-hormone-inhibiting hormone) 		SS, GHIH, or SRIF
Neuroendocrine cells of the Periventricular nucleus
 Inhibit growth-hormone (GH) release from anterior pituitary
Inhibit (moderately) thyroid-stimulating hormone (TSH) release from anterior pituitary

Other hormones secreted from the median eminence include vasopressin, oxytocin, and neurotensin.[26][27][28][29]

Posterior pituitary

In the hypothalamic–pituitary–adrenal axis, neurohypophysial hormones are released from the posterior pituitary, which is actually a prolongation of the hypothalamus, into the circulation.

Secreted hormone Abbreviation Produced by Effect
Oxytocin OXY or OXT Magnocellular neurosecretory cells of the paraventricular nucleus and supraoptic nucleus
Lactation (letdown reflex)
Vasopressin
(antidiuretic hormone) 		ADH or AVP Magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus, magnocellular cells in supraoptic nucleus Increase in the permeability to water of the cells of
collecting duct
in the kidney and thus allows water reabsorption and excretion of concentrated urine

It is also known that hypothalamic–pituitary–adrenal axis (HPA) hormones are related to certain skin diseases and skin homeostasis. There is evidence linking hyperactivity of HPA hormones to stress-related skin diseases and skin tumors.[30]

Stimulation

The hypothalamus coordinates many hormonal and behavioural circadian rhythms, complex patterns of

TRH
is inhibited.

The hypothalamus is responsive to:

  • Light: daylength and
    circadian
    and seasonal rhythms
  • pheromones
  • corticosteroids
  • Neurally transmitted information arising in particular from the heart, enteric nervous system (of the gastrointestinal tract),[31] and the reproductive tract.[citation needed]
  • Autonomic
    inputs
  • Blood-borne stimuli, including
    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

oestrus in many species; in women, synchronized menstruation
may also arise from pheromonal cues, although the role of pheromones in humans is disputed.

Blood-borne stimuli

interleukins to elicit both fever and ACTH secretion, via effects on paraventricular neurons.[citation needed
]

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 the blood into the cerebrospinal fluid (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.[citation needed]

Findings have suggested that

thyroid hormone transporter, supporting the theory that T3 is transported into them. T3 could then bind to the thyroid hormone receptor in these neurons and affect the production of thyrotropin-releasing hormone, thereby regulating thyroid hormone production.[32]

The hypothalamus functions as a type of thermostat for the body.[33] 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.[33] 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.[33]

Steroids

The hypothalamus contains neurons that react strongly to steroids and

TRH
secretion.

Neural

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. The vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension or emptying, to suppress or promote feeding, by signalling the release of leptin or gastrin, respectively. Again this information reaches the hypothalamus via relays in the brainstem.

In addition hypothalamic function is responsive to—and regulated by—levels of all three classical

noradrenaline, dopamine, and serotonin (5-hydroxytryptamine), in those tracts from which it receives innervation. For example, noradrenergic inputs arising from the locus coeruleus have important regulatory effects upon corticotropin-releasing hormone
(CRH) levels.

Control of food intake

Peptide hormones and neuropeptides that regulate feeding[34]
Peptides that increase
feeding behavior 		Peptides that decrease
feeding behavior
Ghrelin Leptin
Neuropeptide Y (α,β,γ)-Melanocyte-stimulating hormones
Agouti-related peptide Cocaine- and amphetamine-regulated transcript peptides
Orexins (A,B) Corticotropin-releasing hormone
Melanin-concentrating hormone Cholecystokinin
Galanin Insulin
Glucagon-like peptide 1

The extreme

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:[35]

  1. Lipostatic hypothesis: This hypothesis holds that
    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 act 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
    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, whereas an increase above the set-point inhibits appetite.

Fear processing

The medial zone of hypothalamus is part of a circuitry that controls motivated behaviors, like defensive behaviors.

Fos-labeling showed that a series of nuclei in the "behavioral control column" is important in regulating the expression of innate and conditioned defensive behaviors.[37]

Antipredatory defensive behavior

Exposure to a predator (such as a cat) elicits defensive behaviors in laboratory rodents, even when the animal has never been exposed to a cat.

Fos-labeled cells in the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial nucleus, and in the ventrolateral part of the premammillary nucleus (PMDvl).[39] The premammillary nucleus has an important role in expression of defensive behaviors towards a predator, since lesions in this nucleus abolish defensive behaviors, like freezing and flight.[39][40] The PMD does not modulate defensive behavior in other situations, as lesions of this nucleus had minimal effects on post-shock freezing scores.[40] The PMD has important connections to the dorsal periaqueductal gray, an important structure in fear expression.[41][42] In addition, animals display risk assessment behaviors to the environment previously associated with the cat. Fos-labeled cell analysis showed that the PMDvl is the most activated structure in the hypothalamus, and inactivation with muscimol prior to exposure to the context abolishes the defensive behavior.[39]
Therefore, the hypothalamus, mainly the PMDvl, has an important role in expression of innate and conditioned defensive behaviors to a predator.

Social defeat

Likewise, the hypothalamus has a role in social defeat: Nuclei in medial zone are also mobilized during an encounter with an aggressive conspecific. The defeated animal has an increase in Fos levels in sexually dimorphic structures, such as the medial pre-optic nucleus, the ventrolateral part of ventromedial nucleus, and the ventral premammilary nucleus.[5] Such structures are important in other social behaviors, such as sexual and aggressive behaviors. Moreover, the premammillary nucleus also is mobilized, the dorsomedial part but not the ventrolateral part.[5] Lesions in this nucleus abolish passive defensive behavior, like freezing and the "on-the-back" posture.[5]

Additional images

  • Human brain left dissected midsagittal view
    Human brain left dissected midsagittal view
  • Location of the hypothalamus
    Location of the hypothalamus

See also

References

  1. ^ Boeree CG. "The Emotional Nervous System". General Psycholoty. Retrieved 18 April 2016.
  2. PMID 33910896
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  3. ^ "NCI Dictionary of Cancer Terms". National Cancer Institute.
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  8. PMID 8277003
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  9. ISBN 978-1437703245
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  10. ^ "Enlarged view of the hypothalamus". psycheducation.org. Jim Phelps. Archived from the original on 15 December 2005. Retrieved 7 February 2020.
  11. The University of Texas at Dallas
    . Retrieved 7 February 2020.
  12. ISBN 978-1416045748
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  13. PMID 19776281
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  14. ISBN 9780071481274
    . Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus.  ... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory ... It also appears that histamine is involved in the regulation of feeding and energy balance.
  15. ^ Brain Research Bulletin 35:323–327, 1994
  16. ^
    PMID 2606795
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  17. PMID 25987976
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  20. ^
    PMID 22396398
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  21. PMID 16410296
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  22. ^ Bowen R. "Overview of Hypothalamic and Pituitary Hormones". Retrieved 5 October 2014.
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  24. ISBN 978-0-7817-7817-6
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  26. PMID 3968510
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  27. PMID 10719209
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  29. S2CID 17941978
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  30. ^ Jung Eun Kim; Baik Kee Cho; Dae Ho Cho; Hyun Jeong Park (2013). "Expression of Hypothalamic–Pituitary–Adrenal Axis in Common Skin Diseases: Evidence of its Association with Stress-related Disease Activity". National Research Foundation of Korea. Retrieved 4 March 2014.
  31. PMID 21750565
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  32. S2CID 33268046
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  33. ^
    ISBN 978-0-07-146633-2
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  34. ISBN 9780071481274
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  35. PMID 178168
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  36. S2CID 10167219
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  37. S2CID 12303256
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  38. S2CID 8063630
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  39. ^
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  41. PMID 1279669
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  42. S2CID 24690642
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Further reading

External links
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