Human placental lactogen
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Human placental lactogen (hPL), also called human chorionic somatomammotropin (HCS), is a
polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
l hormone, the human form of
placental lactogen Placental lactogen, also called chorionic somatomammotropin, is a polypeptide placental hormone, part of the somatotropin family. Its structure and function is similar to that of growth hormone. It modifies the metabolic state of the mother during ...
(
chorionic The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It develops from an outer fold on the surface of the yolk sac, which lies outside the zona pellucida (in mammals), known as the vitelline ...
somatomammotropin). Its structure and function are similar to those of human
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
. It modifies the metabolic state of the mother during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...
to facilitate energy supply to the
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal dev ...
. hPL has anti-
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
properties. hPL is a hormone secreted by the
syncytiotrophoblast Syncytiotrophoblast (from the Greek 'syn'- "together"; 'cytio'- "of cells"; 'tropho'- "nutrition"; 'blast'- "bud") is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nu ...
during pregnancy. Like
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
, hPL is encoded by genes on
chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...
q22-24. It was identified in 1963.


Structure

hPL
molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quant ...
is 22 125  Da and contains single chain consisting of 191
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
residues that are linked by two
disulfide bonds In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
and the structure contains 8 helices. A crystal structure of hPL was determined by
X-ray diffraction X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
to a resolution of 2.0  Å.


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 A multiple birth is the culmination of one multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such ...
. Little hPL enters the fetal circulation. Its
biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
is 15 minutes.


Physiologic function

hPL affects the metabolic system of the maternal organism in the following manners: * In a
bioassay A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (''in vivo''), or on living cells or tissues(''in vitro''). A bioassay can be either quantal or quantitative, dir ...
, hPL mimics the action of
prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pi ...
, yet it is unclear whether hPL has any role in human
lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...
. * Metabolic: ** ↓ maternal
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
sensitivity (insulin resistance), leading to an increase in maternal
blood glucose level Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the bl ...
s. ** ↓ maternal glucose utilization, which helps ensure adequate fetal nutrition (the mother responds by increasing beta cells). Chronic
hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
leads to a rise in hPL. ** ↑
lipolysis Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important ...
with the release of
free fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s. With fasting and release of hPL, free fatty acids become available for the mother as free fatty acids do not cross the placenta, so that relatively more
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
can be utilized by the fetus. With sustained fasting, maternal
ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...
s formed from free fatty acids can cross the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
and be used by the fetus. These functions help support fetal nutrition even in the case of maternal
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
. hPL is a potent
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
of the
prolactin receptor The prolactin receptor (PRLR) is a type I cytokine receptor encoded in humans by the ''PRLR'' gene on chromosome 5p13-14. It is the receptor for prolactin (PRL). The PRLR can also bind to and be activated by growth hormone (GH) and human placental ...
and a weak agonist of the
growth hormone receptor Growth hormone receptor is a protein that in humans is encoded by the ''GHR'' gene. GHR orthologs have been identified in most mammals. Structure Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The recep ...
.


Prolactin-like activity

hPL has been found to bind to the prolactin receptor with equal affinity to that of prolactin in rabbit milk fat globule membrane, and hPL and prolactin have been found to possess very similar lactogenic activity ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' in mouse and rat
mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in ...
explant In biology, explant culture is a technique to organotypically culture cells from a piece or pieces of tissue or organ removed from a plant or animal. The term ''explant'' can be applied to samples obtained from any part of the organism. The extracti ...
s. In addition, hPL has been found to stimulate
DNA synthesis DNA synthesis is the natural or artificial creation of deoxyribonucleic acid (DNA) molecules. DNA is a macromolecule made up of nucleotide units, which are linked by covalent bonds and hydrogen bonds, in a repeating structure. DNA synthesis occurs ...
in human mammary fibroadenoma cells transplanted into mice, which suggests that hPL promotes the growth of the human mammary gland similarly to prolactin. 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. 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.


Growth hormone-like activity

hPL has weak actions, similar to those of
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
, causing the formation of
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
tissues in the same way that growth hormone, but 100 times more hPL than growth hormone is required to promote growth. However, hPL has a blood level of more than 50 times that of hGH, hence its effects must not be ignored. 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 Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...
methods have been found to be more reliable. Also, normal pregnancies have been reported with undetectable maternal levels of hPL.


See also

*
Placental lactogen Placental lactogen, also called chorionic somatomammotropin, is a polypeptide placental hormone, part of the somatotropin family. Its structure and function is similar to that of growth hormone. It modifies the metabolic state of the mother during ...
in other species *
Somatotropin family The Somatotropin family is a protein family whose titular representative is somatotropin, also known as growth hormone, a hormone that plays an important role in growth control. Other members include choriomammotropin (lactogen), its placental an ...


References

* *


Further reading

*


External links

* {{Prolactin receptor modulators Peptide hormones Hormones of the placenta Hormones of the pregnant female Human female endocrine system