SECTION 1: BASICS OF ENDOCRINOLOGY
- 1. Hypothalamus
- Bharti Maheshwari
- 2. Pituitary Gland
- Jasmine Lopez, Hilla S
- 3. Pineal Gland
- Suvarna Khadilkar, Vibha More
- 4. Ovaries
- Shobhana Mohandas
- 5. Testies
- Vinit Shah, Omar Akhtar
- 6. Thyroid Gland
- Sujata Misra
- 7. Parathyroid Gland
- Ranu Patni
- 8. Adrenals and the Kidneys
- Yashodhara Pradeep, Renu Singh
- 9. Pancreas
- Suvarna Khadilkar, Suman Kumari
- 10. Human Skin and Adipose Tissue as Endocrine Units and Exercise Physiology
- Suvarna Khadilkar, Sachin Naiknawre
- 11. Placenta and Hormonal Changes in Normal Pregnancy
- Sajana Gogineni, Prashanthi Vemulapalli
- 12. Physiology of Lactation
- Madhuri A Patel, Surekha Tayade, Amrita Singh
The hypothalamus is a region of the brain composed of many small nuclei with diverse functions. It is located above the midbrain and below the thalamus. The hypothalamus makes up the ventral diencephalon. The diencephalon is an embryologic region of the vertebrate neural tube that gives rise to posterior forebrain structures. Various nuclei of the hypothalamus secrete and synthesize neurohormones, act as a conduit between the nervous and endocrine systems via the pituitary gland (hypophysis)which regulate homeostatic functions such as hunger, thirst, body temperature, and circadian rhythms.1
The hypothalamus occupies the ventral diencephalon (Fig. 1) and is composed of numerous fiber tracts and nuclei situated symmetrically about the third ventricle. In sagittal section, the hypothalamus is roughly diamond shaped; although its boundaries are not sharply demarcated, its perimeters can be correlated using neuroanatomic landmarks.2
Rostrally, the hypothalamus extends from the anterior commissure, lamina terminalis, and optic chiasma and caudally to the periaqueductal gray matter of the midbrain, approximated by (from ventral to dorsal) the mammillary bodies, interpeduncular fossa, and cerebral peduncles. See figures 2, and 3.
Structural Anatomy2
The nuclei of the hypothalamus (Fig. 4 and Table 1) are organized into the following three subdivisions:
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Anterior (or chiasmatic) region, which extends between the lamina terminalis and the anterior infundibular recess.Fig.3: Sagittal section of the hypothalamus, with schematic boundary landmarksAbbreviations: AC: Anterior commissure; PC: posterior commissure; LT: lamina terminalis; OC: optic chiasm; MB: mammillary bodies; IS: infundibular stalk; TC: tuber cinereum; MT: mammillothalamic tract; PF: postcommissural fornix
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Median (or tuberal) region, which proceeds to the anterior column of the fornix
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Posterior (or mammillary) region, which stretches to the caudal mammillary bodies.
These subdivisions are derived primarily from the hypothalamic blood supply.
The anterior hypothalamus is supplied by branches of the anterior cerebral and anterior communicating arteries; the tuberal hypothalamus is supplied by the posterior communicating artery; and the mammillary region is supplied by the posterior communicating, posterior cerebral, and basilar arteries.
The outputs of the hypothalamus can be divided into two categories:
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Neural projections
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Endocrine hormones.
Table 1 Details of hypothalamic nuclei RegionAreaNucleusFunction 8AnteriorMedialMedial preoptic nucleusRegulates the release of gonadotropic hormones from the adenohypophysisContains the sexually dimorphic nucleus, which releases GnRH, differential development between sexes is based upon in utero testosterone levelsSupraoptic nucleus (SO)Vasopressin releaseParaventricular nucleus (PV)Thyrotropin-releasing hormone releaseCorticotropin-releasing hormone releaseOxytocin releaseAnterior hypothalamic nucleus (AH)ThermoregulationPantingSweatingThyrotropin inhibitionSuprachiasmatic nucleus (SC)Circadian rhythmsLateralLateral preoptic nucleusLateral nucleus (LT)Thirst and hungerPart of supraoptic nucleus (SO)TuberalMedialDorsomedial hypothalamic nucleus (DM)Blood PressureHeart RateGI stimulationVentromedial nucleus (VM)Satiety Neuroendocrine controlArcuate nucleus (AR)Growth hormone-releasing hormone (GHRH)FeedingDopamineLateralLateral nucleus (LT)Thirst and hungerLateral tuberal nucleiPosteriorMedialMammillary nuclei (part of mammillary bodies) (MB)MemoryPosterior nucleus (PN)Increase blood pressurePupillary dilationShiveringVasopressin releaseLateralLateral nucleus (LT)
Neural Projections
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Projections to areas rostral to the hypothalamus are carried by the mammillothalamic tract, the fornix and terminal stria.
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Projections to areas of the sympathetic motor system (lateral horn spinal segments T1-L2/L3) are carried by the hypothalamospinal tract and they activate the sympathetic motor pathway.
Neuroendocrine Function
The hypothalamus has a central neuro-endocrine function mainly by its control of the anterior pituitary, which in turn regulates various endocrine glands and organs. Releasing hormones/factor are produced in hypothalamus nuclei then transported along axons to either the median eminence or the posterior pituitary, where they are stored and released as needed.5,7 Detailed account of various releasing hormones secreted by hypothalamus are given in Tables 2 and 3.
Hypothalamic-Adenohypophyseal (Anterior Pituitary) Axis
In the hypothalamic-adenohypophyseal axis, releasing hormones, also known as hypophysiotropic or hypothalamic hormones are released from the median eminence, into the hypophyseal portal system, which carries them to the anterior pituitary where they exert their regulatory functions on the secretion of adenohypopyseal hormones (Fig. 5).4,10
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Hypothalamic-Neurohypophyseal (Posterior Pituitary) Axis
In the hypothalamic-neurohypophyseal axis, neurohypophysial hormones are released from the posterior pituitary, which is actually a prolongation of the hypothalamus, into the circulation.
Clinical Relevance
Hypothalamic-adenohypophyseal (Anterior Pituitary) Axis
The hypothalamic–pituitary–gonadal axis (HPG axis) refers to the effects of the hypothala-mus, pituitary gland, and gonads as a 8whole because these glands often behave in cooperation (Fig. 6). This axis controls development, reproduction, and aging. Hypothalamic pituitary ovarian axis (H-P-O axis) becomes fully active by the age of 13 to 14 years, before that hypothalamus remains dormant due to inhibitory effect of adrenal cortex and higher cortical centers.16-18 Gonadotropin-releasing hormone (GnRH) which is first described by schally and Guillemin in 1971 as decapeptide, is secreted by median eminence and arcuate nucleus of hypothalamus and released at nerve ending near tuber cinerium. It affects the release of FSH and LH from anterior pituitary. GnRH has very short half life 2 to 4 minutes so it is difficult to measure. It is released in pulsatile manner and its secretion varies in frequency and amplitude at different phases of menstrual cycle (Fig. 7 and table 4). Its frequency is one in 60 minutes in follicular phase which slows down to 1 in 180 minutes in luteal phase.
Action of GnRH depends on its mode of release. Its continuous release causes down regulation of ovarian functions resulting in suppression of gonadotropins while pul-satile secretion causes up regulation as in puberty. Hypothalamus is also controlled by higher cortical centers especially temporal lobe. Emotional stress disturbs menstrual cycle by affecting H-P-O axis. Epinephrine and estrogen stimulate whereas dopamine, serotonin, opioids and gonadotropins inhibit release of GnRH by hypothalamus.6,12
Hypothalamic Dysfunction
Disorders of the hypothalamic–pituitary–gona-dal axis are classified by the World Health Organization (WHO) as:
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WHO group I of ovulation disorders: Hypothalamic–pituitary failure.
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WHO group II of ovulation disorders: Hypothalamic–pituitary dysfunction.WHO group II is the most common cause of ovulation disorders, and the most common causative member is polycystic ovary syndrome (PCOS).11,13-15
Table 4 LH pulses estimations of frequency and amplitudes: Indirect way of assessing GnRH pulses Pulse mean amptitudePulse mean frequencyEarly follicular phase06.5IU/L90 minutesMid follicular phase05.0 IU/LLate follicular phase07.2 IU/L60-70 minutesEarly luteal phase15.0 IU/L100 minutesMid luteal phase12.2 IU/LLate luteal phase08.0 IU/L200 minutes
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Precocious puberty
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Hirsuitism
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Endometriosis
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Premenstrual syndrome
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Fibroid.
Injuries or diseases affecting the hypothalamus may produce symptoms of pituitary dysfunction or diabetes insipidus; in the latter disorder, the absence of vasopressin, which promotes the reabsorption of water in the kidneys, induces the rapid loss of water from the body through frequent urination. Hypothalamic disease can also cause insomnia and fluctuations in body temperature.
The best-known variant of hypothalamic anatomy and function leads to Kallmann syndrome, a condition characterized by delayed or absent puberty and anosmia. Under normal circumstances, gonadotropin-releasing hormone–secreting neurons migrate to the hypothalamus (primarily the arcuate and paraventricular nuclei) from the olfactory placode during embryogenesis. Failure of this migration results in an absence of these hypothalamic neurons, with downstream effects on the hypothalamic-pituitary-gonadal axis, mediated by the anterior pituitary gland. Although this deficiency is not evident grossly, a diminution in paraventricular nucleus volume is microscopically evident.7-9
Numerous disease processes may impinge on the hypothalamus, causing secondary detriment of normal function. Tumors of the hypothalamus, pituitary gland, or suprasellar region may impinge on nuclei and fiber tracts, disrupting the endocrine conduit between the hypothalamus and pituitary gland and globally modifying normal hormone concentrations. The optic chiasm is particularly susceptible to pressure from expanding tumors or inflammatory masses in the hypothalamus or the pituitary gland which result in visual defects or blindness. Systemic infiltrative disease may also affect the hypothalamus or pituitary, disrupting function and distorting anatomy.
Certain developmental disorders (Prader-Willi and Bardet-Biedl syndromes) are known to arise in part from disrupted hypothalamic function, but are not associated with aberrations in hypothalamic anatomy. The lateral hypothalamic nucleus is severely affected by Huntington disease, and neuronal loss in the area has even been posited as a marker for disease progression. Histologic changes of the mammillary nucleus occur with Alzheimer and Parkinson diseases, but no gross changes or microscopic cell loss have been observed. In females, the volume of the arcuate nucleus—a critical component of the hypothalamic-pituitary-gonadal axis—is significantly increased in postmenopausal women, an effect recapitulated by pathophysiologic hypogonadal states. Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration. Single mutations usually lead to changes in binding ability of the hormone and receptor leading to inactivation or over activation. These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors.9,10
Summary
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Hypothalamus is a very small but extremely important part of diencephalon, involved in mediation of endocrine, autonomic and behavioral functions.
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It has 3 well defined areas—supraoptic, tuberal and mammilary region which are further divided in many regions and nuclei
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Hypothalamus is connected to anterior lobe of pituitary through hypothalamo-portal vessels and with posterior lobe of pituitary by supraoptic and paraventricular nucleus.
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It secretes many important hormones like GnRH, corticotropin releasing of hormone (CRH), prolactin inhibitory factor (PIF), thyrotropin-releasing hormone (TRH), growth hormone releasing hormone, melanocyte releasing hormone, vasopressin and oxytocin.
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One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and ovarian cycles. In females, the positive feedback loop between estrogen and luteinizing hormone helps to prepare the follicle in the ovary and the uterus for ovulation and implantation.
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Hypothalamus also regulates homeostatic functions such as hunger, thirst, body temperature, and circadian rhythms.
References
- Carpenter MB. Core text of neuroanatomy, 4th edn. Williams and wilkins: Baltimore, Md: 1991.
- Lechan RM, Toni R. Functional anatomy of hypothalamus and pituitary. endotext.org.november 2008.
- Charlton H. “Hypothalamic control of anterior pituitary function: a history”. J Neuroendocrinol. 2008; 20 (6):641-6.doi:10.1111/j. 1365-2826.2008. 01718. x. PMID 18601683.adakkadath.
- Meethal S, Atwood CS. The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain. Cell Mol Life Sci. 2005; 62 (3): 257-70. doi: 10.1007/s00018-004-4381-3. PMID 15723162.
- Katja Hoehn, Marieb Elaine Nicpon. Human anatomy and physiology. Pearson Benjamin Cummings: San Francisco. 2007; pp.1090-1110. ISBN 0-8053-5909-5.
- Veldhuis JD, Keenan DM, Liu PY, Iranmanesh A, Takahashi PY, Nehra AX. “The aging male hypothalamic-pituitary-gonadal axis: pulsatility and feedback”. Mol Cell Endocrinol. 2009; 299 (1): 14-22. doi:10.1016/j.mce.2008.09.005. PMC 2662347. PMID 18838102
- Downs JL, Wise PM. The role of the brain in female reproductive aging. Mol Cell Endocrinol. 2009; 299 (1): 32-8. doi:10.1016/j.mce.2008.11.012. PMC 2692385. PMID 19063938.
- Saleem SN, Said AH, Lee Dh. Lesion of hypothalamus: MR imaging diagnostic features. 2007; 27 (4): 1087-108 [medline].
- Hofman MA. Lifespan changes in the human hypothalamus: Exp Gerontol. 1997; 32 (4-5): 559- 75 [medline]
- Guillebaud J, McVeigh E, Homburg R (2008). Oxford handbook of reproductive medicine and family planning. Oxford University Press: Oxford [Oxfordshire]. ISBN 0-19-920380-6.
- Melmed S, Jameson JL. Disorders of the anterior pituitary and hypothalamus. In Kasper DL, Braunwald E, Fauci AS, et al. Harrison's Principles of Internal Medicine (16th edn). McGraw-Hill: New York, NY . 2005.pp.2076-97.ISBN 0-07-139140-1.
- Howkins and Bourne Shaw's Textbook of Gynaecology, 15th edn, Ch-3, Physiology, Page: 39-41.
- Isidori AM, Giannetta E, Lenzi A. Male hypo-gonadism. Pituitary. 2008; 11 (2): 171-80. doi: 10.1007/s11102-008-0111-9. PMID 18404386.
- Marc A. Fritz, Leon Speroff. Clinical Gynae-cologic Endocrinology and Infertility. 8th edn, ch-5, Neuroendocrinology, Page: 157-70.
- Wiksten-Almströmer M, Hirschberg AL, Hagenfeldt K. Menstrual disorders and associated factors among adolescent girls visiting a youth clinic. Acta Obstet Gynecol Scand. 2007; 86 (1): 65-72. doi:10.1080/00016340601034970. PMID 17230292.
- Weinberg J, Sliwowska JH, Lan N, Hellemans KG. “Prenatal alcohol exposure: fetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome”. J Neuroendocrinol. 2008; 20 (4): 470-88. doi:10.1111/j. 1365-2826.2008. 01669. x. PMID 18266938
- Sower SA, Freamat M, Kavanaugh SI. The origins of the vertebrate hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) endocrine systems: new insights from lampreys”. Gen Comp Endocrinol. 2009; 161 (1): 20-9.
- Vadakkadath Meethal S, Atwood CS. The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain. Cell Mol Life Sci. 2005; 62 (3): 257-70. doi: 10.1007/s00018-004-4381-3.