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{{protein
{{Infobox protein
| Name = chorionic somatomammotropin hormone 1 (placental lactogen)
| Name = chorionic somatomammotropin hormone 1 (human placental lactogen)
| caption =  
| caption = Crystal Structure of Human Placental Lactogen.<ref name="pmid16546209">{{PDB|1Z7C}}; {{cite journal |vauthors=Walsh ST, Kossiakoff AA | title = Crystal structure and site 1 binding energetics of human placental lactogen | journal = J. Mol. Biol. | volume = 358 | issue = 3 | pages = 773–84 |date=May 2006 | pmid = 16546209 | doi = 10.1016/j.jmb.2006.02.038 | url = | issn = }}</ref>
| image =  
| image = 1Z7C.pdb.png
| width =  
| HGNCid = 2440
| HGNCid = 2440
| Symbol = CSH1
| Symbol = CSH1
Line 18: Line 17:
| LocusSupplementaryData = -q24
| LocusSupplementaryData = -q24
}}
}}
{{protein
{{infobox protein
| Name = chorionic somatomammotropin hormone 2
| Name = chorionic somatomammotropin hormone 2
| caption =  
| caption =  
Line 30: Line 29:
| RefSeq = NM_020991
| RefSeq = NM_020991
| UniProt = P01243
| UniProt = P01243
| PDB =  
| PDB = 1Z7C
| ECnumber =  
| ECnumber =  
| Chromosome = 17
| Chromosome = 17
Line 37: Line 36:
| LocusSupplementaryData = -q24
| LocusSupplementaryData = -q24
}}
}}
{{SI}}
__NOTOC__
{{GS}}


'''Human placental lactogen''' ('''hPL'''), also called '''human chorionic somatomammotropin''' ('''HCS'''), is a [[polypeptide]] [[placenta]]l hormone, the human form of [[placental lactogen]] ([[chorionic]] somatomammotropin). Its structure and function are similar to those of human [[growth hormone]]. It modifies the metabolic state of the mother during [[pregnancy]] to facilitate the energy supply of the [[fetus]]. hPL has anti-[[insulin]] properties. hPL is a hormone secreted by the [[syncytiotrophoblast]] during pregnancy.  Like [[human growth hormone]], hPL is encoded by genes on [[chromosome 17]]q22-24. It was identified in 1963.<ref name="pmid14068826">{{cite journal |vauthors=Josimovich JB, Atwood BL, Goss DA | title = Luteotrophic, Immunologic and Electrophoretic Properties of Human Placental Lactogen | journal = Endocrinology | volume = 73 | issue = | pages = 410–20 |date=October 1963 | pmid = 14068826 | doi = 10.1210/endo-73-4-410 }}</ref>


==Structure==
hPL [[molecular mass]] is 22,125 and contains single chain consisting of 191 [[amino acid]] residues that are linked by two [[disulfide bonds]] and the structure contains 8 helices.  A crystal structure of hPL was determined by [[X-ray diffraction]] to a resolution of [[Angstrom|2.0 Å]].<ref name="pmid16546209"/>


==Levels==
hPL is present only during pregnancy, with maternal serum levels rising  in relation to the growth of the fetus and placenta. Maximum levels are reached near term, typically to 5&ndash;7&nbsp;mg/L.  Higher levels are noted in patients with [[multiple gestation]]. Little hPL enters the fetal circulation. Its [[biological half-life]] is 15 minutes.


'''Human placental lactogen''' ('''HPL'''), also called '''human chorionic somatomammotropin''', is a [[polypeptide]] [[placenta]]l hormone. Its structure and function is similar to that of  human [[growth hormone]]. It modifies the metabolic state of the mother during [[pregnancy]] to facilitate the energy supply of the [[fetus]]. HPL is an anti-[[insulin]].
==Physiologic function==
hPL affects the metabolic system of the maternal organism in the following manners:


==Structure==
* In a [[bioassay]] hPL mimics the action of [[prolactin]], yet it is unclear whether hPL has any role in human [[lactation]].
HPL consists of 190 [[amino acids]] that are linked by two disulfite bonds and is secreted by the [[syncytiotrophoblast]] during pregnancy. Its molecular weight is 22,125. Like [[human growth hormone]] HPL is encoded by genes on [[chromosome]] 17q22-24. Its biologic half-life is 15 minutes.
* Metabolic
** ↓ maternal [[insulin]] sensitivity leading to an increase in maternal blood glucose levels.
** ↓ maternal glucose utilization, which helps ensure adequate fetal nutrition (the mother responds by increasing beta cells). Chronic [[hypoglycemia]] leads to a rise in hPL.
** ↑ [[lipolysis]] with  the release of [[free fatty acid]]s.  With fasting and release of hPL, free fatty acids become available for the maternal organism as fuel,  so that relatively more [[glucose]] can be utilized by the fetus. Also, [[ketone]]s formed from free fatty acids can cross the [[placenta]] and be used by the fetus.
These functions help support fetal nutrition even in the case of maternal [[malnutrition]].
 
hPL is a potent [[agonist]] of the [[prolactin receptor]] and a weak agonist of the [[growth hormone receptor]].<ref name="JamesonGroot2015">{{cite book|author1=J. Larry Jameson|author2=Leslie J. De Groot|title=Endocrinology: Adult and Pediatric E-Book|url=https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2490|date=25 February 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-32195-2|pages=2490–}}</ref>


==Levels==
===Prolactin-like activity===
HPL is only present during pregnancy with maternal serum levels rising  in relation to the growth of the fetus and placenta. Maximum levels are reached near term, typically to 5&ndash;7 mg/ml.  Higher levels are noted in patients with [[multiple gestation]]. Little HPL enters the fetal circulation.  
hPL has been found to bind to the prolactin receptor with equal [[affinity (pharmacology)|affinity]] to that of prolactin in rabbit milk fat gobule membrane, and hPL and prolactin have been found to possess very similar lactogenic activity ''[[in vitro]]'' in mouse and rat [[mammary gland]] [[explant culture|explant]]s.<ref name="Neville2013">{{cite book|author=Margaret Neville|title=Lactation: Physiology, Nutrition, and Breast-Feeding|url=https://books.google.com/books?id=hNvTBwAAQBAJ&pg=PA150|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4613-3688-4|pages=150–}}</ref> In addition, hPL has been found to stimulate [[DNA synthesis]] in human mammary [[fibroadenoma]] cells transplanted into mice, which suggests that hPL promotes the growth of the human mammary gland similarly to prolactin.<ref name="Neville2013" /> As hPL circulates at concentrations that are 100-fold higher than those of prolactin during pregnancy, these findings suggest that hPL may play an important role in human [[mammogenesis]] during this time.<ref name="Neville2013" /> However, the relative affinities of hPL and prolactin for the human prolactin receptor have yet to be published and the effects of hPL on normal human mammary epithelial tissue have not yet been investigated, and so a definitive role of hPL in human mammary gland development during pregnancy has not been established at present.<ref name="Neville2013" />


==Function==
===Growth hormone-like activity===
In a [[bioassay]] HPL mimics the action of [[prolactin]], yet it is unclear if HPL has any role in human [[lactation]].
hPL has weak actions similar to those of [[growth hormone]], causing the formation of [[protein]] [[Tissue (biology)|tissues]] in the same way that growth hormone, but 100 times more hPL than growth hormone is required to promote growth.<ref name="isbn81-8147-920-3">{{cite book |author= Guyton and Hall |title=Textbook of Medical Physiology |edition=11 |publisher=Saunders |location=Philadelphia |year=2005 |origyear= |pages= 1033 |quote= This hormone has weak actions similar to those of [[growth hormone]], causing the formation of [[protein]] [[Tissue (biology)|tissues]] in the same way that growth hormone. |isbn=81-8147-920-3 |oclc= |doi= |url= |accessdate=}}</ref> An enhancer for the human placental lactogen gene is found 2 kb downstream of the gene and participates in the cell-specific control gene expression.


HPL affects the metabolic system of the maternal organism. HPL increases production of [[insulin]] and [[IGF-1]] and increases [[insulin resistance]] and [[carbohydrate]] intolerance. Chronic [[hypoglycemia]] leads to a rise in HPL.  HPL induces [[lipolysis]] with  the release of [[free fatty acid]]s, increase in [[insulin]]  secretion and [[insulin resistance]].  With fasting and release of HPL, free fatty acids become available for the maternal organism as fuel,  so that relatively more [[glucose]] can be utilized by the fetus. Also, [[ketone]]s formed from free fatty acids can cross the [[placenta]] and be used by the fetus. These events support energy supply to the fetus in states of [[starvation]].
==Clinical measurement==
While hPL has been used as an indicator of fetal well-being and growth, other [[fetal testing]] methods have been found to be more reliable.{{citation needed|date=September 2012}} Also, normal pregnancies have been reported with undetectable maternal levels of hPL.


==Clinical measurement of HPL==
==See also==
While HPL has been used as an indicator of  fetal well-being and growth, other fetal monitoring methods have been found to be more reliable. Also, normal pregnancies have been reported with undetectable maternal levels of HPL.
*[[Placental lactogen]] in other species
*[[Somatotropin family]]


==References==
==References==
* Speroff L, Glass RH, Kase NG.  Clinical Gynecologic Endocrinology and Infertility. Sixth edition. Lippincott Williams & Wilkins, Baltimore, MD 1999. ISNB 0-683-30379-1.
{{reflist}}
* {{cite web |url=http://www.rcsb.org/pdb/explore/explore.do?structureId=1Z7C |title=RCSB Protein Data Bank - Structure Summary for 1Z7C - Crystal Structure of Human Placental Lactogen |format= |work= |accessdate=}}
* {{cite web |url=http://mend.endojournals.org/cgi/content/full/11/9/1223 |title=Human Chorionic Somatomammotropin Enhancer Function Is Mediated by Cooperative Binding of TEF-1 and CSEF-1 to Multiple, Low-Affinity Binding Sites  |format= |work= |accessdate=}}
 
== Further reading ==
* {{cite book |vauthors=Speroff L, Glass RH, Kase NG | title = Clinical gynecologic endocrinology and infertility | edition = Sixth | language = | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 1999 | origyear = | pages = | quote = | isbn = 0-683-30379-1 | oclc = | doi = | url = | accessdate = }}


==External links==
==External links==
*{{MeshName|Human+Placental+Lactogen}}
*{{MeshName|Human+Placental+Lactogen}}


{{Template:Hormones}}
{{Hormones}}
{{Signaling peptide/protein receptor modulators}}
{{GH/IGF-1 axis signaling modulators}}


[[Category:Peptide hormones]]
[[Category:Peptide hormones]]
[[Category:Placental hormones]]
[[Category:Hormones of the placenta]]
[[Category:Endocrinology]]
[[Category:Hormones of the pregnant female]]
{{WikiDoc Help Menu}}
[[Category:Human female endocrine system]]
{{WikiDoc Sources}}
 
[[de:Humanes Plazentalaktogen]]

Revision as of 15:25, 28 July 2017

chorionic somatomammotropin hormone 1 (human placental lactogen)
File:1Z7C.pdb.png
Crystal Structure of Human Placental Lactogen.[1]
Identifiers
SymbolCSH1
Entrez1442
HUGO2440
OMIM150200
RefSeqNM_001317
UniProtQ6PF11
Other data
LocusChr. 17 q22-q24
chorionic somatomammotropin hormone 2
Identifiers
SymbolCSH2
Entrez1443
HUGO2441
OMIM118820
PDB1Z7C
RefSeqNM_020991
UniProtP01243
Other data
LocusChr. 17 q22-q24

Human placental lactogen (hPL), also called human chorionic somatomammotropin (HCS), is a polypeptide placental hormone, the human form of placental lactogen (chorionic somatomammotropin). Its structure and function are similar to those of human growth hormone. It modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus. hPL has anti-insulin properties. hPL is a hormone secreted by the syncytiotrophoblast during pregnancy. Like human growth hormone, hPL is encoded by genes on chromosome 17q22-24. It was identified in 1963.[2]

Structure

hPL molecular mass is 22,125 and contains single chain consisting of 191 amino acid residues that are linked by two disulfide bonds and the structure contains 8 helices. A crystal structure of hPL was determined by X-ray diffraction to a resolution of 2.0 Å.[1]

Levels

hPL is present only during pregnancy, with maternal serum levels rising in relation to the growth of the fetus and placenta. Maximum levels are reached near term, typically to 5–7 mg/L. Higher levels are noted in patients with multiple gestation. Little hPL enters the fetal circulation. Its biological half-life is 15 minutes.

Physiologic function

hPL affects the metabolic system of the maternal organism in the following manners:

  • In a bioassay hPL mimics the action of prolactin, yet it is unclear whether hPL has any role in human lactation.
  • Metabolic
    • ↓ maternal insulin sensitivity leading to an increase in maternal blood glucose levels.
    • ↓ maternal glucose utilization, which helps ensure adequate fetal nutrition (the mother responds by increasing beta cells). Chronic hypoglycemia leads to a rise in hPL.
    • ↑ lipolysis with the release of free fatty acids. With fasting and release of hPL, free fatty acids become available for the maternal organism as fuel, so that relatively more glucose can be utilized by the fetus. Also, ketones formed from free fatty acids can cross the placenta and be used by the fetus.

These functions help support fetal nutrition even in the case of maternal malnutrition.

hPL is a potent agonist of the prolactin receptor and a weak agonist of the growth hormone receptor.[3]

Prolactin-like activity

hPL has been found to bind to the prolactin receptor with equal affinity to that of prolactin in rabbit milk fat gobule membrane, and hPL and prolactin have been found to possess very similar lactogenic activity in vitro in mouse and rat mammary gland explants.[4] In addition, hPL has been found to stimulate DNA synthesis in human mammary fibroadenoma cells transplanted into mice, which suggests that hPL promotes the growth of the human mammary gland similarly to prolactin.[4] As hPL circulates at concentrations that are 100-fold higher than those of prolactin during pregnancy, these findings suggest that hPL may play an important role in human mammogenesis during this time.[4] However, the relative affinities of hPL and prolactin for the human prolactin receptor have yet to be published and the effects of hPL on normal human mammary epithelial tissue have not yet been investigated, and so a definitive role of hPL in human mammary gland development during pregnancy has not been established at present.[4]

Growth hormone-like activity

hPL has weak actions similar to those of growth hormone, causing the formation of protein tissues in the same way that growth hormone, but 100 times more hPL than growth hormone is required to promote growth.[5] An enhancer for the human placental lactogen gene is found 2 kb downstream of the gene and participates in the cell-specific control gene expression.

Clinical measurement

While hPL has been used as an indicator of fetal well-being and growth, other fetal testing methods have been found to be more reliable.[citation needed] Also, normal pregnancies have been reported with undetectable maternal levels of hPL.

See also

References

  1. ↑ 1.0 1.1 PDB: 1Z7C​; Walsh ST, Kossiakoff AA (May 2006). "Crystal structure and site 1 binding energetics of human placental lactogen". J. Mol. Biol. 358 (3): 773–84. doi:10.1016/j.jmb.2006.02.038. PMID 16546209.
  2. ↑ Josimovich JB, Atwood BL, Goss DA (October 1963). "Luteotrophic, Immunologic and Electrophoretic Properties of Human Placental Lactogen". Endocrinology. 73: 410–20. doi:10.1210/endo-73-4-410. PMID 14068826.
  3. ↑ J. Larry Jameson; Leslie J. De Groot (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 2490–. ISBN 978-0-323-32195-2.
  4. ↑ 4.0 4.1 4.2 4.3 Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN 978-1-4613-3688-4.
  5. ↑ Guyton and Hall (2005). Textbook of Medical Physiology (11 ed.). Philadelphia: Saunders. p. 1033. ISBN 81-8147-920-3. This hormone has weak actions similar to those of growth hormone, causing the formation of protein tissues in the same way that growth hormone.

Further reading

  • Speroff L, Glass RH, Kase NG (1999). Clinical gynecologic endocrinology and infertility (Sixth ed.). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-683-30379-1.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Human_placental_lactogen&oldid=1417725"