Human placental lactogen (hPL)

July 31, 2022

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Human placental lactogen (hPL), also called human chorionic somatomammotropin (HCS), is a polypeptideplacental 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.
- ^{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. PMID14068826}

Structure

hPL molecular mass is 22 125 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.
- ^{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. 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 5–7 mg/L.
- ^{Hicks, Paul (2000). “Gestational Diabetes in Primary Care”. Medscape General Medicine. 2 (1): 2. PMID 10841628. Retrieved 2018-03-23.}
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 (insulin resistance), 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 mother as free fatty acids do not cross the placenta, so that relatively more glucose can be utilized by the fetus. With sustained fasting, maternal 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.
- ^{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.}

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.
- ^{Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN 978-1-4613-3688-4.}
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.
- ^{Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN 978-1-4613-3688-4.}
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.
- ^{Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN 978-1-4613-3688-4.}
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.
- ^{Margaret Neville (11 November 2013). Lactation: Physiology, Nutrition, and Breast-Feeding. Springer Science & Business Media. pp. 150–. ISBN 978-1-4613-3688-4.}

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.
- ^{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.}
However, hPL has a blood level of more than 50 times that of hGH,
- ^{“Growth Hormone: Reference Range, Interpretation, Collection and Panels”. 2016-06-01.}
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 methods have been found to be more reliable.^{[citation needed]} Also, normal pregnancies have been reported with undetectable maternal levels of hPL.

External links

Human+Placental+Lactogen at the US National Library of Medicine Medical Subject Headings (MeSH)

Hormones

GH/IGF-1 axis signaling modulators

Prolactin receptor modulators

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From Wikpedia where this page was last updated July 25, 2022