Hypothalamus

Hypothalamus in brief

• Hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions.
• One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland.
• It is part of the limbic system and is responsible for regulating certain metabolic processes and other activities of the autonomic nervous system.
• It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland.
• It controls
  • Body temperature
  • Hunger
  • Important aspects of parenting and maternal attachment behaviors
  • Thirst
  • Fatigue
  • Sleep and circadian rhythms

Function

Hormone release

• The hypothalamus has a central neuroendocrine function, most notably by its control of the anterior pituitary, which in turn regulates various endocrine glands and organs. Releasing hormones (also called releasing factors) are produced in hypothalamic nuclei then transported along axons to either the median eminence or the posterior pituitary, where they are stored and released as needed.

Anterior pituitary

Secreted hormone	Produced by	Effect
TRH =Thyrotropin-releasing hormone= Prolactin-releasing hormone	Parvocellular neurosecretory cells of the paraventricular nucleus	Stimulate TSH release from anterior pituitary (primarily) Stimulate prolactin release from anterior pituitary
CRH = Corticotropin-releasing hormone	Parvocellular neurosecretory cells of the paraventricular nucleus	Stimulate ACTH release from anterior pituitary
Dopamine= PIH= Prolactin-inhibiting hormone)	Dopamine neurons of the arcuate nucleus	Inhibit prolactin release from anterior pituitary
GHRH= Growth-hormone-releasing hormone	Neuroendocrine neurons of the Arcuate nucleus	Stimulate GH release from anterior pituitary
GnRH = Gonadotropin-releasing hormone	Neuroendocrine cells of the Preoptic area	Stimulate FSH release from anterior pituitary Stimulate LH release from anterior pituitary
Somatostatin= GHIH= growth-hormone-inhibiting hormone)	Neuroendocrine cells of the Periventricular nucleus	Inhibit GH release from anterior pituitary Inhibit (moderately) TSH release from anterior pituitary

Posterior pituitary = HPA axis

Secreted hormone	Produced by	Effect
OXY = Oxytocin	Magnocellular neurosecretory cells of the paraventricular nucleus and supraoptic nucleus	Uterine contraction Lactation (letdown reflex)
ADH = Vasopressin= Antidiuretic hormone	Magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus, magnocellular cells in supraoptic nucleus	Increase in the permeability to water of the cells of distal tubule and collecting duct in the kidney and thus allows water reabsorption and excretion of concentrated urine

Hypothalamic-pituitary-adrenal axis is related to certain skin diseases and skin homeostasis. Hyperactivity of HPA hormones to stress-related skin diseases and skin tumors.

Stimulation

Hypothalamus coordinates many hormonal and behavioral circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and important behaviors. Therefore it respond to many different signals. Delta wave signalling arising either in the thalamus or in the cortex influences the secretion of releasing hormones; GHRH and prolactin are stimulated whilst TRH is inhibited.

The hypothalamus is responsive to:

• Light: For regulating circadian and seasonal rhythms

• Olfactory stimuli, including pheromones, which are important for sexual reproduction and neuroendocrine function in many species.

• Steroids: Including Gonadal steroids / Corticosteroids: Hypothalamus react strongly to steroids and glucocorticoids.

• Neural signals from Heart/ Enteric nervous system/ Reproductive tract:
  • Cardiovascular stimuli are carried by vagus nerve. 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.
  • Hypothalamus is responsive to levels of all three classical monoamine neurotransmitters inluding (1) Noradrenaline (2) Dopamine (3) Serotonin . E.g. Noradrenergic inputs arising from the locus coeruleus have important regulatory effects upon CRH levels
  • 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 body and aortic arch, and from low-pressure atrial volume receptors, is mediated by others. 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.

• Autonomic inputs

• Hormones including: Leptin / Ghrelin / Angiotensin / Insulin / Pituitary hormones / Cytokines E.G in controlling food uptake
  • T3 could bind to the thyroid hormone receptor in TRH-producing neurons and regulating thyroid hormone production.

• Glucose / Osmolarity: Hypothalamus contains specialized glucose-sensitive neurons, which are important for appetite.

• Stress

• Invading microorganisms by increasing body temperature, resetting the body's thermostat upward. Hypothalamus contains thermosensitive neurons; these are important for TRH secretion.
  • Hypothalamus functions as a type of thermostat for the body. 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.

Hypothalamic disorders

• Hypothalamic disease is a disorder presenting Primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including
  • Anorexia and bulimia eating disorders,
  • Genetic disorders,
  • Physical injuries: Radiation, surgery, head trauma, lesion, tumor

Damages cause:

• Body temperature regulation
• Growth, weight
• Sodium and water balance
• Milk production
• Emotions
• Sleep cycles

List of disorders

Note that almost all of below dysfunctions occure through a bidirectional deviation from normal action of at least two or three site. Therefore in the process of finding a miasm which resembels these disorders, we should consider this bidirectionality as a basic character and do not try to divide it into its component. Understanding this feature, could prevent many misleading theories.

Hypopituitarism

• Hypothalamus and pituitary gland are tightly integrated.
• Damage to the hypothalamus will impact the responsiveness and normal functioning of pituitary.
• Hypothalamic disease may cause insufficient or inhibited signalling to the pituitary leading to deficiencies of one or more of the following hormones:
  • TSH: Thyroidits (EBV, MMP, HCV)
  • ACTH: Abd, Adrenal insufficiency (CMV, EBV, HSV-1, HSV-2, MTB)
  • Beta-endorphin, LH, FSH: Female, Infertility (HPV, MMP, MTB) / Male, In
  • Melanocyte Stimulating Hormones (Skin, Pigmentation: CMV, HSV-1)

Neurogenic diabetes insipidus

• Neurogenic diabetes insipidus may occur due to low levels of ADH production from the hypothalamus.
• Insufficient levels of ADH result in increased thirst and urine output, and prolonged excessive urine excretion increases the risk of dehydration.

Tertiary hypothyroidism

• Thyroid gland is an auxiliary organ to the hypothalamus-pituitary system.
• TRH produced by the hypothalamus signals to the pituitary to release TSH, which then stimulates the thyroid to secrete T₄ and T₃ thyroid hormones.
• Secondary hypothyroidism occurs when TSH secretion from the pituitary is impaired
• Tertiary hypothyroidism is the deficiency or inhibition of TRH.
• Thyroid hormones are responsible for metabolic activity. Insufficient production of the thyroid hormones result in suppressed metabolic activity and weight gain. Hypothalamic disease may therefore have implications for obesity.

Developmental disorders

• GHRH is another releasing factor secreted by the hypothalamus.
• GHRH stimulates the pituitary gland to secrete GH, which has various effects on body growth and sexual development.
• Insufficient GH production may cause poor somatic growth, precocious puberty or gonadotropin deficiency, failure to initiate or complete puberty, and is often associated with rapid weight gain, low T₄, and low levels of sex hormones.

Sleep disorders

• Non-24-hour sleep-wake syndrome, a disabling condition in which one's sleep/wake cycle is longer, or rarely, shorter, than the standard 24 hours, is thought to involve or be caused by, at least in some cases, an abnormal functioning of the suprachiasmatic nucleus (SCN) in the hypothalamus.