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    Topic review

    Placental Lactogen

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    Submitted by: Rafał Sibiak

    Definition

    Placental lactogen (PL) is a peptide hormone classified as a member of a growth hormone gene family. PL is secreted throughout pregnancy by both animal and human specialized endocrine cells. It is involved in the regulation of a range of gestational adaptations.

    1. Introduction

    Placental lactogen, also known as chorionic somatotropin, is a peptide hormone produced during pregnancy, in humans and other animals, by specialized endocrine cells.

    More specifically, PL is synthesized by:

    • syncytiotrophoblast cells in humans,
    • trophoblast giant cells in rats and mice,
    • and trophoblastic binucleate cells in cows and sheep [1][2][3][4][5][6].

    PL is classified as a member of the somatotropin family, which also includes growth hormone (GH), prolactin (PRL), and placental growth hormone, mainly due to the similarities observed in their molecular structure [1][7][8][9]. More details about the PL family genes and encoded proteins have been described by Handwerger et al. in their excellent review [10]. In humans, PL mainly binds to prolactin receptors and with a much lower affinity to growth hormone receptors [10]. Moreover, specific PL receptors have been found in human fetal skeletal muscles [11]. Similar to humans, PL in ruminants binds with a high affinity to PRL receptors, but it also has a high affinity to GH receptors [7]. Mouse PL has a higher affinity to PRL receptors than GH receptors; however, in contrast to humans, in mice and rats, there are two types of active PL with distinct biological activity [9][12][13][14]. Due to the described differences, the results of studies performed in other species cannot be directly extrapolated to humans.

    PL is detectable in both umbilical cord blood samples and maternal blood from the first trimester of physiological pregnancy, and its concentrations increase in the later stages of fetal and placental development [8][11][15]. Although the PL expression is only present in placental tissue cells, it is considered to play a significant role in the regulation of both maternal and fetal metabolic adaptations throughout the pregnancy [9][16]. The secretion of PL, as well as other placental hormones, could promote the state of systemic insulin resistance and subsequently be responsible for the elevation of maternal blood glucose levels to facilitate the supply of energetic substrates to the fetus [17][18][19].

    2. Human Placental Lactogen (hPL)

    hPL is believed to be involved in the regulation of both maternal and fetal gestational adaptation. However, the majority of hPL is released into the maternal circulation. To compartmentalize the hPL release into maternal and fetal circulation, Linnemann et al. used the dual in vitro perfusion of an isolated cotyledon, with hPL concentrations measured in the perfusates and the placental tissue prior to and after perfusion. According to their results, only 0.05% of hPL is transferred to the developing fetus, with the remaining percentage being released into the maternal circulation [20]. hPL is also detectable in the amniotic fluid. However, its concentrations are generally lower compared with the maternal serum [21]. In a group of term newborns (40th week), those born via vaginal delivery had significantly lower levels of hPL in both the umbilical vein and umbilical artery compared with those born through cesarean section [22]. hPL blood concentrations in multiple pregnancies tend to rise compared with single pregnancies [23].

    Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the hPL secretion pattern. Whereas obesity is most often associated with lower placental hPL expression, diabetes results in increased hPL blood levels [24][25][26]. Disruptions in hPL secretion are reported to be associated with an increased prevalence of fetal growth abnormalities - growth retardation and fetal macrosomia [27][28].

    This entry is adapted from 10.3390/jcm9041142

    References

    1. Walter L. Miller; Norman L. Eberhardt; Structure and Evolution of the Growth Hormone Gene Family. Endocrine Reviews 1983, 4, 97-130, 10.1210/edrv-4-2-97.
    2. David Hill; Placental control of metabolic adaptations in the mother for an optimal pregnancy outcome. What goes wrong in gestational diabetes?. Placenta 2018, 69, 162-168, 10.1016/j.placenta.2018.01.002.
    3. Teresa N. Faria; Santanu Deb; Simon Kwok; Frank Talamantes; Michael J. Soares; Ontogeny of placental lactogen-I and placental lactogen-II expression in the developing rat placenta. Developmental Biology 1990, 141, 279-291, 10.1016/0012-1606(90)90384-u.
    4. M Yamaguchi; L Ogren; H Endo; G Thordarson; R M Bigsby; F Talamantes; Production of mouse placental lactogen-I and placental lactogen-II by the same giant cell.. Endocrinology 1992, 131, 1595-1602, 10.1210/endo.131.4.1396305.
    5. M.C. Lacroix; P. Bolifraud; D. Durieux; A. Pauloin; M. Vidaud; G. Kann; Placental growth hormone and lactogen production by perifused ovine placental explants: regulation by growth hormone-releasing hormone and glucose.. Biology of Reproduction 2002, 66, 555-561, 10.1095/biolreprod66.3.555.
    6. S. Handwerger; M. Freemark; The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development.. Journal of Pediatric Endocrinology and Metabolism 2000, 13, 343-356, 10.1515/jpem.2000.13.4.343.
    7. D. J. Hill; M. Freemark; A. J. Strain; S. Handwerger; R. D. G. Milner; Placental Lactogen and Growth Hormone Receptors in Human Fetal Tissues: Relationship to Fetal Plasma Human Placental Lactogen Concentrations and Fetal Growth*. The Journal of Clinical Endocrinology & Metabolism 1988, 66, 1283-1290, 10.1210/jcem-66-6-1283.
    8. Andrea V. Alvarez-Oxiley; Noelita M. De Sousa; Jean-François Beckers; Native and recombinant bovine placental lactogens.. Reproductive Biology 2008, 8, 85-106, 10.1016/s1642-431x(12)60006-0.
    9. William H. Walker; Susan L. Fitzpatrick; Hugo Barrera-Saldaña; Grady F. Saunders; Diana Reséndez-Pérez; The Human Placental Lactogen Genes: Structure, Function, Evolution and Transcriptional Regulation. Endocrine Reviews 1991, 12, 316-328, 10.1210/edrv-12-4-316.
    10. Stuart Handwerger; CLINICAL COUNTERPOINT: The Physiology of Placental Lactogen in Human Pregnancy*. Endocrine Reviews 1991, 12, 329-336, 10.1210/edrv-12-4-329.
    11. G Untergasser; Martin Hermann; Holger Rumpold; G Pfister; P Berger; An unusual member of the human growth hormone/placental lactogen (GH/PL) family, the testicular alternative splicing variant hPL-A2: recombinant expression revealed a membrane-associated growth factor molecule. Molecular and Cellular Endocrinology 2000, 167, 117-125, 10.1016/s0303-7207(00)00287-2.
    12. Peter Colosi; Frank Talamantes; Daniel I. H. Linzer; Molecular Cloning and Expression of Mouse Placental Lactogen I Complementary Deoxyribonucleic Acid. Molecular Endocrinology 1987, 1, 767-776, 10.1210/mend-1-11-767.
    13. P. Colosi; G. Marr; J. Lopez; L. Haro; L. Ogren; F. Talamantes; Isolation, purification, and characterization of mouse placental lactogen.. Proceedings of the National Academy of Sciences 1982, 79, 771-775, 10.1073/pnas.79.3.771.
    14. Toshio Harigaya; William C. Smith; Frank Talamantes; Hepatic Placental Lactogen Receptors During Pregnancy in the Mouse*. Endocrinology 1988, 122, 1366-1372, 10.1210/endo-122-4-1366.
    15. K. W. Kastrup; H. J. Andersen; P. Lebech; SOMATOMEDIN IN NEWBORNS AND THE RELATIONSHIP TO HUMAN CHORIONIC SOMATOTROPIN AND FETAL GROWTH. Acta Paediatrica 1978, 67, 757-762, 10.1111/j.1651-2227.1978.tb16257.x.
    16. Dorothee Newbern; Michael Freemark; Placental hormones and the control of maternal metabolism and fetal growth. Current Opinion in Endocrinology & Diabetes and Obesity 2011, 18, 409-416, 10.1097/med.0b013e32834c800d.
    17. Edmond A. Ryan; Louise Enns; Role of Gestational Hormones in the Induction of Insulin Resistance*. The Journal of Clinical Endocrinology & Metabolism 1988, 67, 341-347, 10.1210/jcem-67-2-341.
    18. Linda A. Barbour; Jianhua Shao; Liping Qiao; Leslie K. Pulawa; Dalan R. Jensen; Andrzej Bartke; Maureen Garrity; Boris Draznin; Jacob E. Friedman; Human placental growth hormone causes severe insulin resistance in transgenic mice.. American Journal of Obstetrics and Gynecology 2002, 186, 512-517, 10.1067/mob.2002.121256.
    19. Sharon Ladyman; R. A. Augustine; David R. Grattan; Hormone interactions regulating energy balance during pregnancy. Journal of Neuroendocrinology 2010, 22, 805-817, 10.1111/j.1365-2826.2010.02017.x.
    20. Knud Linnemann; Antoine Malek; Ruth Sager; Werner F. Blum; Henning Schneider; C. Fusch; Leptin Production and Release in the Dually in Vitro Perfused Human Placenta 1. The Journal of Clinical Endocrinology & Metabolism 2000, 85, 4298-4301, 10.1210/jcem.85.11.6933.
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    23. Paul E. Lebech; Birgit Borggaard; SERUM LEVELS OF HUMAN CHORIONIC SOMATOMAMMOTROPIN (HCS) IN NORMAL AND ABNORMAL PREGNANCIES. European Journal of Endocrinology 1974, 77, S35-S43, 10.1530/acta.0.075s035.
    24. Yan Jin; Hana Vakili; Song Yan Liu; Savas Menticoglou; Margaret E. Bock; Peter A. Cattini; Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity. American Journal of Physiology-Endocrinology and Metabolism 2018, 315, E435-E445, 10.1152/ajpendo.00042.2018.
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    26. N Soler; SERIAL DETERMINATIONS OF HUMAN PLACENTAL LACTOGEN IN THE MANAGEMENT OF DIABETIC PREGNANCY. The Lancet 1975, 306, 54-57, 10.1016/s0140-6736(75)90496-1.
    27. M Gardner; Rl Goldenberg; Sp Cliver; Lr Boots; HJ Hoffman; Maternal serum concentrations of human placental lactogen, estradiol and pregnancy specific β1 — glycoprotein and fetal growth retardation. American Journal of Obstetrics and Gynecology 1995, 172, 293, 10.1016/0002-9378(95)90801-3.
    28. Michael Small; Alan Cameron; C Burnett Lunan; Angus C MacCuish; Macrosomia in Pregnancy Complicated by Insulin-Dependent Diabetes Mellitus. Diabetes Care 1987, 10, 594-599, 10.2337/diacare.10.5.594.
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