View source for Hypophyseal portal system

{{short description|System of blood vessels}}
{{Infobox Vein
|  Name        = Hypophyseal portal system
|  Latin       = venae portales hypophysiales
|  Image       = Grays pituitary.png
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|  Caption2    = 
|  DrainsFrom  = 
|  Source      = 
|  DrainsTo    = 
|  Artery      = 
}}

The '''hypophyseal portal system''' is a system of [[blood vessels]] in the [[microcirculation]] at the base of the [[brain]], connecting the [[hypothalamus]] with the [[anterior pituitary]]. Its main function is to quickly transport and exchange [[hormone]]s between the hypothalamus [[arcuate nucleus]] and anterior pituitary gland. The [[capillary|capillaries]] in the portal system are [[Capillary#Fenestrated|fenestrated]] (have many small channels with high [[vascular permeability]]) which allows a rapid exchange between the hypothalamus and the pituitary. The main hormones transported by the system include [[gonadotropin-releasing hormone]], [[corticotropin-releasing hormone]], [[growth hormone–releasing hormone]], and [[thyrotropin-releasing hormone]].

==Structure==
The blood supply and direction of flow in the hypophyseal portal system has been studied over many years on laboratory animals and human cadaver specimens with injection and [[vascular corrosion casting]] methods. Short portal vessels between the neural and anterior pituitary lobes provide an avenue for rapid hormonal exchange.<ref name="gross">{{cite journal|pmid=8481959|year=1993|last1=Gross|first1=PM|title=Topography of short portal vessels in the rat pituitary gland: A scanning electron-microscopic and morphometric study of corrosion cast replicas|journal=Cell and Tissue Research|volume=272|issue=1|pages=79–88|last2=Joneja|first2=MG|last3=Pang|first3=JJ|last4=Polischuk|first4=TM|last5=Shaver|first5=SW|last6=Wainman|first6=DS|doi=10.1007/bf00323573|s2cid=23657199}}</ref><ref name="shaver">{{cite journal|pmid=1571958|year=1992|last1=Shaver|first1=SW|title=Morphology and function of capillary networks in subregions of the rat tuber cinereum|journal=Cell and Tissue Research|volume=267|issue=3|pages=437–48|last2=Pang|first2=JJ|last3=Wainman|first3=DS|last4=Wall|first4=KM|last5=Gross|first5=PM|doi=10.1007/bf00319366|s2cid=27789146}}</ref><ref name="ciofi">{{cite journal|pmid=19837874|pmc=2819742|year=2009|last1=Ciofi|first1=P|title=Brain-endocrine interactions: A microvascular route in the mediobasal hypothalamus|journal=Endocrinology|volume=150|issue=12|pages=5509–19|last2=Garret|first2=M|last3=Lapirot|first3=O|last4=Lafon|first4=P|last5=Loyens|first5=A|last6=Prévot|first6=V|last7=Levine|first7=J. E.|doi=10.1210/en.2009-0584}}</ref> Specifically within and between the pituitary lobes is anatomical evidence for confluent interlobe vessels, including [[venule]]s providing blood from the anterior to the neural lobe, and capillary shunts exchanging blood between the intermediate and neural lobes.<ref name=gross/> Such microvascular structures indicate moment-to-moment streams of information between lobes of the pituitary gland.<ref name=gross/>

Results of other studies showed that the neural hypophyseal stalk and ventromedial region of the hypothalamic [[arcuate nucleus]] receive arterial blood from ascending and descending infundibular branches and capillaries, coming from arteries of the superior hypophyseal arterial system.<ref name=ciofi/> Small ascending vessels arising from the [[anastomosis|anastomoses]] that connect the upper with the lower hypophyseal arterial system also supply blood to hypophyseal vessels. Many of these branches are continuous between the proximal arcuate nucleus and anterior pituitary, enabling rapid hormone exchange.<ref name=shaver/><ref name=ciofi/><ref name="Molin" /> Other evidence indicates that capillary [[perivascular space]]s of the [[median eminence]] and arcuate nucleus are contiguous, potentially facilitating hormonal messages between systemic blood and the [[Anatomical terms of location|ventral]] hypothalamus.<ref name=shaver/>

===Development===
Proper hormone secretion is crucial for the growth of the developing [[fetus]]. In order to allow a controlled hormone secretion in the developing organs of the fetus, stimulating hormones must be exchanged in the regulating structures in the brain in early stages of the development. Hormone-exchanging blood vessels between the hypothalamus and the pituitary gland, similar to those of the hypophyseal portal system, can be observed in early developmental stages of the fetus. In the current literature, most research is conducted using mice as model species. In such studies, development of the hypophyseal portal system begins as early as 14.5 [[Days post coitum|dpc (days post coitum)]]. Two populations of [[pericytes]] arise from the [[mesoderm]] and the [[neuroectoderm]] and form at the approximate location of the portal system in what will eventually become the mature brain.<ref>Fiordelisio, Tatiana; Rizzoti, Karine; Samper, Patrick; Lafont, Chrstel; Davis, Shannon; Mollard, Patrice E. “Developmental Program of the Pituitary Portal System.” Endocrine Society’s 97th Annual Meeting and Expo. March 2015. San Diego, CA</ref> Additionally, in research involving human fetuses it has been observed that the hypophyseal portal system fully develops by week 11.5 of the human fetal gestation period. This was determined by injecting a silicone rubber compound into specimens of various stages of gestation. In a specimen at week 11.5, the median eminence and infundibular stem contained the compound, suggesting the existence of the fully developed portal system.<ref>{{Cite journal|last1=Thliveris|first1=James A.|last2=Currie|first2=R. William|date=1980-04-01|title=Observations on the hypothalamo-hypophyseal portal vasculature in the developing human fetus|journal=American Journal of Anatomy|language=en|volume=157|issue=4|pages=441–444|doi=10.1002/aja.1001570411|pmid=7405878|issn=1553-0795|doi-access=free}}</ref> Further research in this area would help determine whether or not development could be complete at an even earlier stage.

==Function==
[[Peptide]]s released near the [[median eminence]] from hypothalamic nuclei are transported to the anterior pituitary, where they apply their effects. Branches from the internal carotid artery provide the blood supply to the pituitary. The [[Superior hypophyseal artery|superior hypophyseal arteries]] form the primary capillary plexus that supplies blood to the median eminence. From this capillary system, the blood is drained in hypophyseal portal veins into the secondary plexus. The peptides released at the median eminence enter the primary plexus capillaries. From there, they are transported to the anterior pituitary via hypophyseal portal veins to the secondary plexus. The secondary plexus is a network of fenestrated sinusoid capillaries that provide blood to the anterior pituitary. The cells of the anterior pituitary express specific [[G protein-coupled receptors]] that bind to the neuropeptides, activating intracellular [[Second messenger system|second messenger]] cascades that produce the release of anterior pituitary hormones.<ref name=Molin>Molina, Patricia.E. (2010). Endocrine Physiology. Lange. (3, p. 31). {{ISBN|978-0-07-161301-9}}.</ref>

The following is a list of hormones that rely on the hypophyseal portal system to indirectly mediate their function by acting as a means of transportation from various nuclei of the hypothalamus to the anterior pituitary.<ref>{{Cite book|title=Human physiology : an integrated approach|author=Silverthorn, Dee Unglaub|others=Johnson, Bruce R., Ober, William C., Ober, Claire E., Silverthorn, Andrew C.|isbn=9780321981226|edition=Seventh|location=[San Francisco]|oclc=890107246|year = 2016}}</ref>
* Gonadotropin-releasing hormone ([[Gonadotropin-releasing hormone|GnRH]]): regulates the release of [[Follicle-stimulating hormone|follicle stimulating hormone]] and [[luteinizing hormone]] from the anterior pituitary; this pathway plays a critical role in reproductive activity and development
* Corticotropin-releasing hormone ([[Corticotropin-releasing hormone|CRH]]): regulates the release of [[adrenocorticotropic hormone]] from the anterior pituitary; this cascade is primarily responsible for stress responses
* Growth hormone-releasing hormone ([[Growth hormone–releasing hormone|GHRH]]): regulates the release of [[growth hormone]] from the anterior pituitary; as the name suggests, its main function is to help control cell growth, metabolism, and reproduction
* Thyrotropin-releasing hormone ([[Thyrotropin-releasing hormone|TRH]]): regulates the release of [[thyroid-stimulating hormone]] from the anterior pituitary; functions to mediate various responses in the thyroid gland, including additional hormone synthesis

==Clinical significance==
Over- or under-function as well as insufficiencies of the hypothalamus or the pituitary gland can cause a negative effect on the ability of the hypophyseal portal system to exchange hormones between both structures rapidly. This can have major effects on the respective target glands, making it impossible for them to carry out their functions properly. Occlusions and other issues in the blood vessels of the hypophysial portal system can also cause complications in the exchange of hormones between the hypothalamus and the pituitary gland.

The hypophyseal portal system also plays an important role in several diseases involving the pituitary and central nervous system. In several cases of hypophyseal and pituitary metastatic tumors, the portal system acts as the pathway for [[metastasis]] from the hypothalamus to the pituitary. That is, cancerous cells from the hypothalamus multiply and spread to the pituitary using the hypophyseal portal system as a means of transportation. However, because the portal system receives an indirect supply of arterial blood, tumor formation in the anterior pituitary is less likely than in the posterior pituitary. This is because the posterior pituitary is vascularized by direct arterial blood flow.<ref>{{Cite journal|last1=Ravnik|first1=Janez|last2=Smigoc|first2=Tomaz|last3=Bunc|first3=Gorazd|last4=Lanisnik|first4=Bostjan|last5=Ksela|first5=Ursa|last6=Ravnik|first6=Maja|last7=Velnar|first7=Tomaz|title=Hypophyseal metastases: A report of three cases and literature review|journal=Neurologia I Neurochirurgia Polska|volume=50|issue=6|pages=511–516|doi=10.1016/j.pjnns.2016.08.007|pmid=27633123|year=2016|url=https://journals.viamedica.pl/neurologia_neurochirurgia_polska/article/view/61195}}</ref><ref>{{Cite journal|last1=Komninos|first1=John|last2=Vlassopoulou|first2=Varvara|last3=Protopapa|first3=Despina|last4=Korfias|first4=Stefanos|last5=Kontogeorgos|first5=George|last6=Sakas|first6=Damianos E.|last7=Thalassinos|first7=Nicolas C.|date=2004-02-01|title=Tumors Metastatic to the Pituitary Gland: Case Report and Literature Review|journal=The Journal of Clinical Endocrinology & Metabolism|volume=89|issue=2|pages=574–580|doi=10.1210/jc.2003-030395|pmid=14764764|issn=0021-972X|doi-access=free}}</ref> [[Pituitary apoplexy]] is described as hemorrhaging or reduction of blood supply to the pituitary gland. The physiological mechanisms of this condition have not been clearly defined in current research.<ref>{{Cite journal|last1=Briet|first1=Claire|last2=Salenave|first2=Sylvie|last3=Bonneville|first3=Jean-François|last4=Laws|first4=Edward R.|last5=Chanson|first5=Philippe|date=2015-12-01|title=Pituitary Apoplexy|journal=Endocrine Reviews|volume=36|issue=6|pages=622–645|doi=10.1210/er.2015-1042|pmid=26414232|issn=0163-769X|doi-access=free}}</ref> It has been suggested, nonetheless, that damage to the pituitary stalk leads to an obstruction of blood flow in the hypophyseal portal system and contributes to this defective state.<ref>{{Cite journal|last1=Billeci|first1=Domenico|last2=Marton|first2=Elisabetta|last3=Giordan|first3=Enrico|title=Post-traumatic pituitary apoplexy: Case presentation and review of literature|journal=Interdisciplinary Neurosurgery|volume=7|pages=4–8|doi=10.1016/j.inat.2016.10.006|year=2017|doi-access=free|url=https://www.openaccessrepository.it/record/36652/files/fulltext.pdf|archive-url=https://web.archive.org/web/20210428215545/https://www.openaccessrepository.it/record/36652/files/fulltext.pdf|url-status=dead|archive-date=April 28, 2021}}</ref> In [[Erdheim–Chester disease]], cells of the immune system called [[histiocyte]]s proliferate at an abnormal rate causing a plethora of symptoms and, in more severe cases, death. The disruption of the hypophyseal portal system has been implicated as the mechanism for several symptoms involving the central nervous symptom, most notably [[diabetes insipidus]].<ref>{{Cite journal|last1=Mazor|first1=Roei D.|last2=Manevich-Mazor|first2=Mirra|last3=Shoenfeld|first3=Yehuda|date=2013-09-08|title=Erdheim–Chester disease: a comprehensive review of the literature|journal=Orphanet Journal of Rare Diseases|volume=8|pages=137|doi=10.1186/1750-1172-8-137|pmid=24011030|pmc=3849848|issn=1750-1172 |doi-access=free }}</ref>

==See also==
{{Portal|Medicine}}
{{Anatomy-terms}}
* [[Hypopituitarism]]

==References==
{{Reflist}}

==External links==
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/anatomy.html Functional Anatomy of the Hypothalamus and Pituitary Gland, Colorado State University] {{Webarchive|url=https://web.archive.org/web/20150909201719/http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/anatomy.html |date=2015-09-09 }}

{{Veins of the head and neck}}
{{Endocrine system anatomy}}

[[Category:Central nervous system]]
[[Category:Angiology]]
[[Category:Endocrine system anatomy]]