Endocrine - Placenta Development

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Pregnancy Test

For complete notes on placenta development and function see Placenta Development.

Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | pineal | hypothalamus‎ | pituitary | thyroid | parathyroid | thymus | pancreas | adrenal | endocrine gonad‎ | endocrine placenta | other tissues | Stage 22 | endocrine abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 1903 Pig Adrenal | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Adrenal | 1927 Hypophyseal fossa | 1930 Adrenal | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1935 Pineal | 1937 Pineal | 1935 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal

Lecture - Placenta Development

Placenta Links: placenta | Lecture - Placenta | Lecture Movie | Practical - Placenta | implantation | placental villi | trophoblast | maternal decidua | uterus | endocrine placenta | placental cord | placental membranes | placenta abnormalities | ectopic pregnancy | Stage 13 | Stage 22 | placenta histology | placenta vascular | blood vessel | cord stem cells | 2013 Meeting Presentation | Placenta Terms | Category:Placenta
Historic Embryology - Placenta 
1883 Embryonic Membranes | 1907 Development Atlas | 1909 | 1910 Textbook | 1917 Textbook | 1921 Textbook | 1921 Foetal Membranes |1921 human | 1921 Pig implantation | 1922 Single placental artery | 1923 Placenta Review | 1939 umbilical cord | 1943 human and monkey | 1944 chorionic villus and decidua parietalis | 1946 placenta ageing | 1960 first trimester placenta | 1960 monkey | 1972 Placental circulation | Historic Disclaimer
  • Human chorionic gonadotrophin (hCG) - like leutenizing hormone, supports corpus luteum in ovary, pregnant state rather than menstrual, maternal urine in some pregnancy testing
  • Human chorionic somatommotropin (hCS) - or placental lactogen stimulate (maternal) mammary development
  • Human chorionic thyrotropin (hCT)
  • Human chorionic corticotrophin (hCACTH)
  • progesterone and estrogens - support maternal endometrium
  • Progesterone-Associated Endometrial Protein (PAEP, pregnancy protein-14, PP14) - glycoprotein hormone from decidualized endometrium with possible immunoregulatory activities.
  • IGF binding protein-1 (IGFBP-1) peptide hormone from decidualized endometrium increases during the first trimester, peaks during the second trimester, falls briefly, and peaks a second time before term.[1]
  • Relaxin - corpus luteum then placenta in the first trimester, then declines in the second trimester. Binds to relaxin receptors on both the decidua and cytotrophoblasts.

  • Placenta - Maternal (decidua) and Fetal (trophoblastic cells, extra-embryonic mesoderm) components
  • Endocrine function - maternal and fetal precursors, synthesis and secretion
    • Protein Hormones - chorionic gonadotropin (hCG), chorionic somatomammotropin (hCS) or placental lactogen (hPL), chorionic thyrotropin (hCT), chorionic corticotropin (hCACTH)
      • hCG - up to 20 weeks, fetal adrenal cortex growth and maintenance
      • hCS – rise through pregnancy, stimulates maternal metabolic processes, breast growth
    • Steroid Hormones - progesterone (maintains pregnancy), estrogens (fetal adrenal/placenta)

Some Recent Findings

Model male second trimester androsterone synthesis
Model male second trimester androsterone synthesis[2]
  • Expression of steroidogenic enzymes in human placenta according to the gestational age[3] "Female sex steroid hormones, including estradiol (E2) and progesterone (P4), serve significant physiological roles in pregnancy. In particular, E2 and P4 influence placenta formation, maintain pregnancy and stimulate milk production. These hormones are produced by ovaries, adrenal glands and the placenta, of which the latter is a major endocrine organ during pregnancy. However, the mechanism of hormone production during pregnancy remains unclear. In the present study, the regulation of steroid hormones and steroidogenic enzymes was examined in human placenta according to gestational age. In human placental tissues, expression levels of steroidogenic enzymes were determined with reverse transcription‑quantitative polymerase chain reaction and western blotting. The mRNA and protein expression of CYP17A1, HSD17B3 and CYP19A1, which are associated with the synthesis of dehydroepiandrosterone (DHEA) and E2, was elevated at different gestational ages in human placenta. In addition, to evaluate the correlation between serum and placental‑produced hormones, steroid hormone levels, including pregnenolone (PG), DHEA, P4, testosterone (T) and E2, were examined in serum and placenta. Serum and placenta expression of DHEA and E2 increased with gestational age, whereas T and P4 were differently regulated in placenta and serum. To confirm the mechanism of steroidogenesis in vitro, placental BeWo cells were treated with E2 and P4, which are the most important hormones during pregnancy. The mRNA and protein expression of steroidogenic enzymes was significantly altered by E2 in vitro. These results demonstrated that concentration of steroid hormones was differently regulated by steroidogenic enzymes in the placenta depending on the type of the hormones, which may be critical to maintain pregnancy."
  • Alternative (backdoor) androgen production and masculinization in the human fetus[2] "Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. ...Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that placental progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans."
More recent papers  
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Search term: Endocrine Placenta

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Review - The endocrine function of human placenta: an overview[4] "During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications."
  • The feto-placental unit, and potential roles of dehydroepiandrosterone (DHEA) in prenatal and postnatal brain development[5] "Synthesis of dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental oestrogen production, and may also be important for modulating the effects of glucocorticoids on the developing brain. ... Together, the studies outlined in this review indicate that the androgen DHEA is an important hormone of adrenal and Central Nervous System (CNS) origin in the fetal and postnatal spiny mouse. Disturbance of the development of these fetal tissues, and/or of the relationship between the fetal adrenal gland and placenta during pregnancy, may have significant consequences for fetal development, placental function, and maturation of the brain. It is proposed that such disturbances of normal adrenal function could account for some of the neuropathologies that arise in juvenile and adult offspring following illness and stress experienced by the mother during pregnancy."
  • Human Chorionic Gonadotropin Induces Human Macrophages to Form Intracytoplasmic Vacuoles Mimicking Hofbauer Cells in Human Chorionic Villi[6] The most characteristic morphological feature of macrophages in the stroma of placental villi, known as Hofbauer cells, is their highly vacuolated appearance. They also show positive immunostaining for human chorionic gonadotropin (hCG)."
  • Serum biomarkers for predicting pregnancy outcome in women undergoing IVF[7] "This study was performed to assess the prognostic value of serum hCG, progesterone, and inhibin A levels measured at 11 days post-ET for predicting pregnancy outcome in women participating in IVF. Between May 2005 and April 2008, sera were obtained from 70 infertile women who underwent IVF-ET at 11 days post-ET and stored. HCG, progesterone, and inhibin A levels were measured by commercial enzyme-linked immunosorbent assay kits. The predictive accuracy of hCG, progesterone, and inhibin A levels for establishment of intrauterine pregnancy and ongoing pregnancy was calculated by receiver-operating characteristic curve analysis. For the prediction of intrauterine and ongoing pregnancy, serum hCG was better than progesterone and inhibin A. The predictive performance of progesterone and inhibin A was similar. The serum progesterone and inhibin A levels were significantly correlated each other (r=0.915, p=0.010)."

Human Chorionic Gonadotrophin

Trophoblast hCG function

Human chorionic gonadotrophin (hCG) like leutenizing hormone, supports corpus luteum in ovary, pregnant state rather than menstrual. Presence in the maternal urine is the basis of some pregnancy testing.

The level of the hyperglycosylated form (HCG-H) is high during the implantation phase and then decreases to the end of the first trimester.[8] In addition to the implantation role it has suggested immune cell modulation and endothelial functions.

Trophoblast cell hCG.jpg

Trophoblast cell hCG

hCG Links: hCG | Trophoblast hCG function | Trophoblast cell hCG | implantation | placenta | NIH - The History of the Pregnancy Test

Placental Estrogen

Maternal late pregnancy shows a large increase in estriol levels.[9]

  1. fetal adrenal - gland production of dehydroepiandrosterone sulphate (DHEAS)
  2. fetal liver - conversion to 16α-OH-DHEAS
  3. placenta - sulphate removal to allow aromatization to estriol.

Placental estrogen, mainly estriol, suppresses gonadotropin secretion from the maternal pituitary gland. Maternal estrogen levels are often a useful indicator of fetal well being.[10][11]

  • Uterus - stimulates growth of the myometrium, antagonizes the myometrial-suppressing activity of progesterone.
  • Mammary Gland - stimulates mammary gland ductal and alveolar growth.
  • Fetal Ovary - stimulates development of female fetal ovary.[12]

A second role for fetal adrenal DHEA-S is possible regulation of the effects of glucocorticoids on the developing brain.[5]

Links: adrenal

Placental Progesterone

The fetal placenta production of progesterone throughout the second and third trimesters is a key to maintaining the uterus in the non-menstral pregnant state.[13] A second identified immunological role is in modulation of cytokine production.[14]

Human Chorionic Somatommotropin

Human chorionic somatommotropin hormone (hCS, CSH) is also called placental lactogen, due to its role in stimulating maternal mammary development, there may be little growth (somatogen) effects of this hormone. The hormone is structurally similar to both growth hormone (GH) and prolactin (PRL} and binds strongly to PRL receptors but weakly to GH receptors.

Links: mammary gland

Cortiticotropin Releasing Hormone

The placenta synthesises urocortins (Ucn 1, Ucn 2, Ucn 3), cortiticotropin releasing hormone (CRH) analogues.[15] Appears to be produced by chorio-decidual cells.


The placenta and corpus luteum produce relaxin, a 6 kDa peptide hormone structurally similar to insulin. The hormone stimulates in early pregnancy both uterine growth and vascularization associated with implantation. It is also postulated to have other roles in the menstrual cycle[16]

Links: implantation

Other Factors

  • placental tachykinins
  • neurokinin B
  • endokinin


  1. Rutanen EM. (2000). Insulin-like growth factors in obstetrics. Curr. Opin. Obstet. Gynecol. , 12, 163-8. PMID: 10873115
  2. 2.0 2.1 O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, Savchuk I, Monteiro A, Soffientini U, Johnston ZC, Bellingham M, Hough D, Walker N, Filis P & Fowler PA. (2019). Alternative (backdoor) androgen production and masculinization in the human fetus. PLoS Biol. , 17, e3000002. PMID: 30763313 DOI.
  3. Hong SH, Kim SC, Park MN, Jeong JS, Yang SY, Lee YJ, Bae ON, Yang HS, Seo S, Lee KS & An BS. (2019). Expression of steroidogenic enzymes in human placenta according to the gestational age. Mol Med Rep , 19, 3903-3911. PMID: 30896833 DOI.
  4. Costa MA. (2016). The endocrine function of human placenta: an overview. Reprod. Biomed. Online , 32, 14-43. PMID: 26615903 DOI.
  5. 5.0 5.1 Quinn TA, Ratnayake U, Dickinson H, Castillo-Melendez M & Walker DW. (2016). The feto-placental unit, and potential roles of dehydroepiandrosterone (DHEA) in prenatal and postnatal brain development: A re-examination using the spiny mouse. J. Steroid Biochem. Mol. Biol. , 160, 204-13. PMID: 26485665 DOI.
  6. Yamaguchi M, Ohba T, Tashiro H, Yamada G & Katabuchi H. (2013). Human chorionic gonadotropin induces human macrophages to form intracytoplasmic vacuoles mimicking Hofbauer cells in human chorionic villi. Cells Tissues Organs (Print) , 197, 127-35. PMID: 23128164 DOI.
  7. Kim JH, Shin MS, Yi G, Jee BC, Lee JR, Suh CS & Kim SH. (2012). Serum biomarkers for predicting pregnancy outcome in women undergoing IVF: human chorionic gonadotropin, progesterone, and inhibin A level at 11 days post-ET. Clin Exp Reprod Med , 39, 28-32. PMID: 22563548 DOI.
  8. Evans J. (2016). Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor. Am. J. Reprod. Immunol. , 75, 333-40. PMID: 26676718 DOI.
  9. Raeside JI. (2017). A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine. Yale J Biol Med , 90, 449-461. PMID: 28955183
  10. Rainey WE, Rehman KS & Carr BR. (2004). The human fetal adrenal: making adrenal androgens for placental estrogens. Semin. Reprod. Med. , 22, 327-36. PMID: 15635500 DOI.
  11. Parker CR. (1999). Dehydroepiandrosterone and dehydroepiandrosterone sulfate production in the human adrenal during development and aging. Steroids , 64, 640-7. PMID: 10503722
  12. Albrecht ED & Pepe GJ. (2010). Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy. Int. J. Dev. Biol. , 54, 397-408. PMID: 19876841 DOI.
  13. Pavlicev M & Norwitz ER. (2018). Human Parturition: Nothing More Than a Delayed Menstruation. Reprod Sci , 25, 166-173. PMID: 28826363 DOI.
  14. Raghupathy R & Szekeres-Bartho J. (2016). Dydrogesterone and the immunology of pregnancy. Horm Mol Biol Clin Investig , 27, 63-71. PMID: 26812877 DOI.
  15. Fekete EM & Zorrilla EP. (2007). Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: ancient CRF paralogs. Front Neuroendocrinol , 28, 1-27. PMID: 17083971 DOI.
  16. Marshall SA, Senadheera SN, Parry LJ & Girling JE. (2017). The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy. Reprod Sci , 24, 342-354. PMID: 27365367 DOI.


Costa MA. (2016). The endocrine function of human placenta: an overview. Reprod. Biomed. Online , 32, 14-43. PMID: 26615903 DOI.

De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Tal R, Taylor HS, Burney RO, Mooney SB & Giudice LC. (2000). Endocrinology of Pregnancy. , , . PMID: 25905197

John RM. (2013). Epigenetic regulation of placental endocrine lineages and complications of pregnancy. Biochem. Soc. Trans. , 41, 701-9. PMID: 23697929 DOI.

Evain-Brion D & Malassine A. (2003). Human placenta as an endocrine organ. Growth Horm. IGF Res. , 13 Suppl A, S34-7. PMID: 12914725


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Endocrine Terms  
  • adrenocorticotropin - (ACTH or corticotropin) anterior pituitary, peptide hormone
  • antidiuretic hormone - (ADH) hypothalamus, peptide hormone
  • atrial natriuretic factor - (ANP) heart, , peptide hormone
  • corticosteroid binding globulin - (CBG) binds and transports glucocorticoids in the plasma. Globin is synthesised in the liver.
  • dehydroepiandrosterone - (DHEA, androstenolone) The fetal adrenal cortex produces dehydroepiandrosterone sulphate (DHEA-S) used by the placenta to produce estrogens. Postnatally an abundant circulating steroid produced in the adrenal gland. DHEA, androstenedione, and testosterone can be metabolized to epiandrosterone, and etiocholanolone. PMID 15635500]
  • growth hormone - (GH) pituitary, peptide hormone
  • human chorionic gonadotropin - (hCG) pancreas glycoprotein hormone with 2 subunits (alpha and beta joined non covalently). Similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents (regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG). PMID: 19171054 (More? Placenta Development)
  • lutenizing hormone - (LH) pituitary, protein hormone
  • melaocyte stimulating hormone - (MSH) pituitary, peptide hormone
  • Rathke's pouch - The transient folding surface ectoderm from roof of the oral cavity that will form the anterior pituitary (hypophysis). in later development the connection with the oral cavity is lost. Named after Martin Heinrich Rathke (1793 – 1860) a German embryologist and anatomist. (More? Pituitary Development)
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Cite this page: Hill, M.A. (2024, June 19) Embryology Endocrine - Placenta Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Placenta_Development

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