In the adult, large neurosecretory cells of the supraoptic (SON) and paraventricular nucleus (PVN) project to the neurohypophysis from the hypothalamus.
Stage 22 Human Hypothalamus
In the early embryo, neuroectoderm of the forebrain (prosenecephalon) primary brain vesicle divides to form two secondary brain vesicles, telencephalon (endbrain, cortex) and diencephalon. From the diencephalon ventro-lateral wall, intermediate zone proliferation generates the primordial hypothalamus.
Growth hormone (GH) secretion from the pituitary is controlled in many different ways, including positive/negative regulation of synthesis and release by the hypothalamus. Hypothalamic GH releasing hormone (GHRH) activates and somatostatin suppresses growth hormone synthesis and release.
Other key nuclei within the hypothalamus include the sexually dimorphic nucleus (SDN, intermediate nucleus, INAH-1), suprachiasmatic nucleus (SCN) and tuberal lateral nucleus (NTL).
The SDN is twice as large in young male adults as in young females. At birth 20% of the adult SDN cell number is present, from then until 2-4 years of age cell numbers increase equally rapidly in both sexes. After this age cell numbers start to decrease in girls, creating the sex difference.
The SCN is the clock of the brain and shows circadian and seasonal fluctuations in vasopressin-expressing cell numbers. (SDN and SCN text modified from: Swaab, 1995)
The tuberal lateral nucleus (NTL) is involved in feeding behavior and energy metabolism.
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Caqueret A, Yang C, Duplan S, Boucher F, Michaud JL. Looking for trouble: a search for developmental defects of the hypothalamus. Horm Res. 2005;64(5):222-30.
"The hypothalamus is a critical integrator of several homeostatic processes that are required for the survival of vertebrates. ...We predict that disruption of hypothalamic development is a common, previously unsuspected cause of disorders of homeostatic processes such as obesity and high blood pressure."
Central regulation of thyroid hormone feedback Alkemade A, Friesema EC, Unmehopa UA, Fabriek BO, Kuiper GG, Leonard JL, Wiersinga WM, Swaab DF, Visser TJ, Fliers E. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus. J Clin Endocrinol Metab. 2005 Jul;90(7):4322-34. Paper proposes 3 possible routes for thyroid hormone feedback on TRH neurons in the human paraventricular nucleus (PVN)
Koutcherov Y, Mai JK, Paxinos G. Hypothalamus of the human fetus. J Chem Neuroanat. 2003 Dec;26(4):253-70.
"organization of the human hypothalamus was studied in 31 brains aged from 9 weeks of gestation (w.g.) to newborn" (More? Human Development Overview)
Markakis EA. Development of the neuroendocrine hypothalamus. Front Neuroendocrinol. 2002 Jul;23(3):257-91.
"...The rat hypothalamus is generated predominantly from the third ventricular neuroepithelium in a "lateral early to medial late" pattern dictated perhaps by the medially receding third ventricle. Neuroendocrine neurons seem to exhibit a delayed migrational strategy, showing relatively early birthdates, although they are located in the latest-generated, periventricular nuclei. Several homeobox genes seem to play a role in hypothalamic development, and gene knockout experiments implicate a number of genes of importance in the generation of the neuroendocrine cell type."
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents
Embryo Images Unit: Embryo Images Online | Nervous System Development | Prosencephalon | Hypothalamus
hypothalamus
Note the weeks listed below are "weeks of gestation" and differ from embryonic/fetal age by approximately 2 weeks.
9 - 10 and 11 - 14 weeks lateral hypothalamic zone structures differentiate - give rise to the lateral hypothalamus (LH) and posterior hypothalamus.
10 weeks dorsomedial nucleus differentiation.
14 weeks supramamillary nucleus appears transiently and disappears by 16 weeks.
18 weeks perifornical nucleus differentiation (from LH neurons which remain anchored in the perifornical position while most of the LH cells are displaced laterally).
13 - 16 weeks ventromedial nucleus differentiates three principal parts: ventrolateral, dorsomedial and the shell.
13 - 16 weeks medial mamillary body differentiation into lateral and medial.
15-17, 18-23 and 24-33 weeks hypothalamic core differentiation.
< 33 weeks (late second trimester) differentiation of midline zone structures: suprachiasmatic, arcuate and paraventricular nuclei.
(Data from immunohistochemistry study of 31 brains aged from 9 weeks of gestation to newborn: Koutcherov Y, Mai JK, Paxinos G. Hypothalamus of the human fetus. J Chem Neuroanat. 2003 Dec;26(4):253-70. Review.)
Xu C, Fan CM.
Expression of Robo/Slit and Semaphorin/Plexin/Neuropilin family members in the developing hypothalamic paraventricular and supraoptic nuclei.
Gene Expr Patterns. 2008 Jun 21. [Epub ahead of print]
PMID: 18617019 [PubMed - as supplied by publisher]
Xu C, Fan CM.
Allocation of paraventricular and supraoptic neurons requires Sim1 function: a role for a Sim1 downstream gene PlexinC1.
Mol Endocrinol. 2007 May;21(5):1234-45. Epub 2007 Mar 13.
PMID: 17356169 [PubMed - indexed for MEDLINE]
The SCN is the clock of the brain and shows circadian and seasonal fluctuations in vasopressin-expressing cell numbers. This circadian system also appears developmentally responsive to light and low intensity lighting can impact upon this developing clock. Rivkees SA. Developing circadian rhythmicity in infants. Pediatr Endocrinol Rev. 2003 Sep;1(1):38-45. "After birth, there is progressive maturation of the circadian system outputs, with pronounced rhythms in sleep-wake and hormone secretion generally developing after two months of age."
The SDN is twice as large in young male adults as in young females. At birth 20% of the adult SDN cell number is present, from then until 2-4 years of age cell numbers increase equally rapidly in both sexes. After this age cell numbers start to decrease in girls, creating the sex difference.
A recent paper has proposed three potential routes as to how thyroid hormone (TH) would feedback on thyroid releasing hormone (TRH) neurons in the human hypothalamus paraventricular nucleus (PVN):
1 local thyroid hormone uptake from vascular compartment within PVN.
2 thyroid hormone uptake from cerebrospinal fluid in third ventricle, followed by transport to TRH neurons in PVN or infundibular nucleus neurons projecting to TRH neurons in PVN.
3 thyroid hormone sensing in infundibular nucleus of mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN.
(Data from: Alkemade A, Friesema EC, Unmehopa UA, Fabriek BO, Kuiper GG, Leonard JL, Wiersinga WM, Swaab DF, Visser TJ, Fliers E. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus. J Clin Endocrinol Metab. 2005 Jul;90(7):4322-34.)
Brn2
Otp control the development by maintaining Brn2 expression.
Sim1
Sonic Hedgehog - (Shh) secreted patterning factor which is expressed in ventral midline hypothalamus neural cells.
Reference: Michaud JL., 2001
Links: Journals | Online Textbooks | Search Textbooks | PubMed | 1999 Refs | Search PubMed | Glossary
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents
NIH Genes & Disease Chapter 41 - Endocrine
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002.
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.
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anterior periventricular nuclei - (aPV)
arcuate nucleus - (ARC)
corticotropin-releasing hormone - (CRH) hormone released by parvocellular neurons into medial eminence (ME) portal vasculature.
magnocellular neurons - neurons located in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON), axons project to the posterior pituitary where they secrete vasopressin (VP) and oxytocin (OT).
paraventricular nucleus - (PVN)
parvocellular neurons - neurons located in the paraventricular nucleus (PVN), axons project to medial eminence (ME) portal vasculature of pituitary and release thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), and somatostatin (SS).
somatostatin - (SS) hormone released by parvocellular neurons into medial eminence (ME) portal vasculature.
Sonic Hedgehog - (Shh) secreted patterning factor which is expressed in ventral midline hypothalamus neural cells.
supraoptic nucleus - (SON)
thyrotropin-releasing hormone - (TRH) hormone released by parvocellular neurons into medial eminence (ME) portal vasculature.
ventromedial nucleus
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How do you link the brain to the endocrine system? The hypothalamus is this key link between brain and the peripheral endocrine system. Neurons from the hypothalamus project down into the posterior pituitary, settting in train a series of endocrine events with significant impact on nearly all body systems.
Please email Dr Mark Hill if you wish to make a comment about this current project.