Human placental lactogen

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chorionic somatomammotropin hormone 1 (human placental lactogen)
1Z7C.pdb.png
Crystal Structure of human placental lactogen. [1]
Identifiers
SymbolCSH1
NCBI gene 1442
HGNC 2440
OMIM 150200
RefSeq NM_001317
UniProt Q6PF11
Other data
Locus Chr. 17 q22-q24
Search for
Structures Swiss-model
Domains InterPro
chorionic somatomammotropin hormone 2
Identifiers
SymbolCSH2
NCBI gene 1443
HGNC 2441
OMIM 118820
PDB 1Z7C
RefSeq NM_020991
UniProt P01243
Other data
Locus Chr. 17 q22-q24
Search for
Structures Swiss-model
Domains InterPro

Human placental lactogen (hPL), also called human chorionic somatomammotropin (hCS) or human chorionic somatotropin, 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 energy supply to 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]

Contents

Structure

hPL molecular mass is 22125  Da 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. [3] Higher levels are noted in patients with multiple gestation. Little hPL enters the fetal circulation. Its biological half-life is 15 minutes. Some women with higher BMI show lower levels of placental lactogen, but whether prenatal health behaviors influence hPL levels or if hPL influences infant birth weight is uncertain. [4]

Physiologic function

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

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. [5]

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 mouse and rat mammary gland explants. [6] 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. [6] 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. [6] 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. [6]

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. [7] However, hPL has a blood level of more than 50 times that of hGH, [8] 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.[ citation needed ]

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.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Endocrine system</span> Hormone-producing glands of a body

The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems.

<span class="mw-page-title-main">Placenta</span> Organ that connects the fetus to the uterine wall

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 maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone that stimulates growth, cell reproduction and cell regeneration

Growth hormone (GH) or somatotropin, also known as human growth hormone 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 human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

<span class="mw-page-title-main">Prolactin</span> Protein family and hormone

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 pituitary gland in response to eating, mating, estrogen treatment, ovulation and nursing. It is secreted heavily in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the immune system and pancreatic development.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.

<span class="mw-page-title-main">Gestational hypertension</span> Medical condition

Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hypertension is defined as having a blood pressure greater than 140/90 on two occasions at least 6 hours apart.

<span class="mw-page-title-main">Diabetes and pregnancy</span> Effects of pre-existing diabetes upon pregnancy

For pregnant women with diabetes, some particular challenges exist for both mother and fetus. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.

<span class="mw-page-title-main">Syncytiotrophoblast</span> Embryonic cell of the placental surface

Syncytiotrophoblast is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother. It is a multinucleate, terminally differentiated syncytium, extending to 13 cm.

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 lactogen (hPL). The PRLR is expressed in the mammary glands, pituitary gland, and other tissues. It plays an important role in lobuloalveolar development of the mammary glands during pregnancy and in lactation.

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 pregnancy to facilitate the energy supply of the fetus.

Metabolic imprinting refers to the long-term physiological and metabolic effects that an offspring's prenatal and postnatal environments have on them. Perinatal nutrition has been identified as a significant factor in determining an offspring's likelihood of it being predisposed to developing cardiovascular disease, obesity, and type 2 diabetes amongst other conditions.

<span class="mw-page-title-main">Growth hormone 2</span> Variant of somatotropin produced by placenta

Growth hormone 2 (GH2), also known more commonly as placental growth hormone (PGH) or growth hormone variant (GH-V), is a protein that in humans is encoded by the GH2 gene. It is produced by and secreted from the placenta during pregnancy, and becomes the predominant form of growth hormone (GH) in the body during this time. Its cogener is growth hormone 1 (GH1), or pituitary growth hormone.

Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life.

<span class="mw-page-title-main">Circumvallate placenta</span> Medical condition

Circumvallate placenta is a rare condition affecting about 1-2% of pregnancies, in which the amnion and chorion fetal membranes essentially "double back" on the fetal side around the edges of the placenta. After delivery, a circumvallate placenta has a thick ring of membranes on its fetal surface. Circumvallate placenta is a placental morphological abnormality associated with increased fetal morbidity and mortality due to the restricted availability of nutrients and oxygen to the developing fetus.

<span class="mw-page-title-main">Maternal physiological changes in pregnancy</span>

Maternal physiological changes in pregnancy are the adaptations that take place during pregnancy that enable the accommodation of the developing embryo and fetus. These are normal physiological adaptations that cause changes in behavior, the functioning of the heart, blood vessels, and blood, metabolism including increases in blood sugar levels, kidney function, posture, and breathing. During pregnancy numerous hormones and proteins are secreted that also have a broad range of effects.

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 analogue; prolactin, which promotes lactation in the mammary gland, and placental prolactin-related proteins; proliferin and proliferin related protein; and somatolactin from various fishes. The 3D structure of bovine somatotropin has been predicted using a combination of heuristics and energy minimisation.

Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus during embryogenesis and the mother, including human chorionic gonadotropin (hCG) and progesterone (P4).

The fetal endocrine system is one of the first systems to develop during prenatal development of a human individual. The endocrine system arises from all three embryonic germ layers. The endocrine glands that produce the steroid hormones, such as the gonads and adrenal cortex, arise from the mesoderm. In contrast, endocrine glands that arise from the endoderm and ectoderm produce the amine, peptide, and protein hormones.

Maternal fetal stress transfer is a physiological phenomenon in which psychosocial stress experienced by a mother during her pregnancy can be transferred to the fetus. Psychosocial stress describes the brain's physiological response to perceived social threat. Because of a link in blood supply between a mother and fetus, it has been found that stress can leave lasting effects on a developing fetus, even before a child is born. According to recent studies, these effects are mainly the result of two particular stress biomarkers circulating in the maternal blood supply: cortisol and catecholamines.

The multigenic complex formed by the human growth hormone (hGH) and the human placental lactogen (hPL) takes part in the process of maternal and fetal metabolism regulation and the following growth and development of the fetus.

References

  1. 1 2 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 (4): 410–20. doi: 10.1210/endo-73-4-410 . PMID   14068826.
  3. Hicks, Paul (2000). "Gestational Diabetes in Primary Care". Medscape General Medicine . 2 (1): 2. PMID   10841628 . Retrieved 2018-03-23.
  4. Garay, Samantha M.; Sumption, Lorna A.; John, Rosalind M. (9 September 2022). "Prenatal health behaviours as predictors of human placental lactogen levels". Frontiers in Endocrinology. 13: 946539. doi: 10.3389/fendo.2022.946539 . PMC   9500170 . PMID   36157466.
  5. 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.
  6. 1 2 3 4 Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN   978-1-4613-3688-4.
  7. 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.
  8. "Growth Hormone: Reference Range, Interpretation, Collection and Panels". 2016-06-01.{{cite journal}}: Cite journal requires |journal= (help)

Further reading