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Licensed Unlicensed Requires Authentication Published by De Gruyter August 29, 2016

The formation and transformation of hormones in maternal, placental and fetal compartments: biological implications

  • Jorge R. Pasqualini EMAIL logo and Gérard S. Chetrite

Abstract

The fetal endocrine system constitutes the earliest system developing in fetal life and operates during all the steps of gestation. Its regulation is in part dependent on the secretion of placental and/or maternal precursors emanating across the feto-maternal interface. Human fetal and placental compartments possess all the enzymatic systems necessary to produce steroid hormones. However, their activities are different and complementary: the fetus is very active in converting acetate into cholesterol, in transforming pregnanes to androstanes, various hydroxylases, sulfotransferases, while all these transformations are absent or very limited in the placenta. This compartment can transform cholesterol to C21-steroids, convert 5-ene to 4-ene steroids, and has a high capacity to aromatize C19 precursors and to hydrolyze sulfates. Steroid hormone receptors are present at an early stage of gestation and are functional for important physiological activities. The production rate of some steroids greatly increases with fetal evolution (e.g. estriol increases 500–1000 times in relation to non-pregnant women). Other hormones, such as glucocorticoids, in particular the stress hormone cortisol, adipokines (e.g. leptin, adiponectin), insulin-like growth factors, are also a key factor for regulating reproduction, metabolism, appetite and may be significant in programming the fetus and its growth. We can hypothesize that the fetal and placental factors controlling hormonal levels in the fetal compartment can be of capital importance in the normal development of extra-uterine life.

References

1. Westin B, Nyberg R, Enhorning G. A technique for perfusion of the previable human fetus. Acta Paediatr 1958;47:339–49.10.1111/j.1651-2227.1958.tb07643.xSearch in Google Scholar

2. Nyberg R, Westin B. An experimental study of the previable human foetus. J Obstet Gynaecol Br Emp 1962;69:831–5.10.1111/j.1471-0528.1962.tb01291.xSearch in Google Scholar

3. Pasqualini JR, Kincl FA, editors. Hormones and the fetus, vol. 1. Oxford: Pergamon Press, 1985:73–172.10.1016/B978-0-08-019708-1.50006-4Search in Google Scholar

4. Archer DF, Mathur RS, Wiqvist N, Diczfalusy E. Quantitative assessment of the de novo sterol and steroid synthesis in the human foeto-placental unit. 2. Synthesis and secretion of steroids and steroid sulphates by the midgestation foetus. Acta Endocrinol (Copenh) 1971;66:666–78.10.1530/acta.0.0660666Search in Google Scholar

5. Mathur RS, Archer DF, Wiqvist N, Diczfalusy E. Quantitiative assessment of the de novo sterol and steroid synthesis in the human foeto-placental unit. I. Synthesis and secretion of cholesterol and cholesterol sulphate. Acta Endocrinol (Copenh) 1970;65:663–74.10.1530/acta.0.0650663Search in Google Scholar

6. Carr BR, Simpson ER. Cholesterol synthesis in human fetal tissues. J Clin Endocrinol Metab 1982;55:447–52.10.1210/jcem-55-3-447Search in Google Scholar

7. Carr BR, Simpson ER. De novo synthesis of cholesterol by the human fetal adrenal gland. Endocrinology 1981;108: 2154–62.10.1210/endo-108-6-2154Search in Google Scholar

8. Pezzi V, Mathis JM, Rainey WE, Carr BR. Profiling transcript levels for steroidogenic enzymes in fetal tissues. J Steroid Biochem Mol Biol 2003;87:181–9.10.1016/j.jsbmb.2003.07.006Search in Google Scholar

9. Klak J, Hill M, Parizek A, Havlikova H, Bicikova M, Hampl R, Fait T, Sulcova J, Pouzar V, Kancheva R, Starka L. Pregnanolone isomers, pregnenolone and their polar conjugates around parturition. Physiol Res 2003;52:211–21.10.33549/physiolres.930317Search in Google Scholar

10. Meeker CI, DeCesaris V, Tulp O. Metabolism of 7- 3 H-pregnenolone in normal human placenta maintained in organ culture. Am J Obstet Gynecol 1971;111:840–5.10.1016/0002-9378(71)90497-2Search in Google Scholar

11. Thomas JL, Berko EA, Faustino A, Myers RP, Strickler RC. Human placental 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase: purification from microsomes, substrate kinetics, and inhibition by product steroids. J Steroid Biochem 1988;31:785–93.10.1016/0022-4731(88)90287-7Search in Google Scholar

12. Guichard A, de Ikonicoff LK, Cedard L. [Delta 5–3 beta hydroxysteroid dehydrogenase activity in the human full term placenta after culture: the effect of chorionic gonatropin]. C R Acad Sci Hebd Seances Acad Sci D 1975;280:1481–4.Search in Google Scholar

13. Tuckey RC. Progesterone synthesis by the human placenta. Placenta 2005;26:273–81.10.1016/j.placenta.2004.06.012Search in Google Scholar

14. Alfaidy N, Li W, MacIntosh T, Yang K, Challis J. Late gestation increase in 11beta-hydroxysteroid dehydrogenase 1 expression in human fetal membranes: a novel intrauterine source of cortisol. J Clin Endocrinol Metab 2003;88:5033–8.10.1210/jc.2002-021915Search in Google Scholar

15. Harada N, Yoshimura N, Honda S. Unique regulation of expression of human aromatase in the placenta. J Steroid Biochem Mol Biol 2003;86:327–34.10.1016/S0960-0760(03)00375-3Search in Google Scholar

16. Wang WS, Liu C, Li WJ, Zhu P, Li JN, Sun K. Involvement of CRH and hCG in the induction of aromatase by cortisol in human placental syncytiotrophoblasts. Placenta 2014;35:30–6.10.1016/j.placenta.2013.10.018Search in Google Scholar PubMed

17. Wang W, Li J, Ge Y, Li W, Shu Q, Guan H, Yang K, Myatt L, Sun K. Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway. Endocrinology 2012;153:2012–22.10.1210/en.2011-1626Search in Google Scholar PubMed

18. Takeyama J, Suzuki T, Hirasawa G, Muramatsu Y, Nagura H, Iinuma K, Nakamura J, Kimura KI, Yoshihama M, Harada N, Andersson S, Sasano H. 17Beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus. J Clin Endocrinol Metab 2000;85:410–6.10.1210/jcem.85.1.6323Search in Google Scholar

19. Tomi M, Eguchi H, Ozaki M, Tawara T, Nishimura S, Higuchi K, Maruyama T, Nishimura T, Nakashima E. Role of OAT4 in Uptake of estriol precursor 16alpha-hydroxydehydroepiandrosterone sulfate Into human placental syncytiotrophoblasts from fetus. Endocrinology 2015;156:2704–12.10.1210/en.2015-1130Search in Google Scholar PubMed

20. Aldemir O, Ozen S, Sanlialp C, Ceylaner S. Are low maternal estriol levels a predictor for pro-opiomelanocortin (POMC) deficiency caused by POMC mutation during pregnancy? Prenat Diagn 2013;33:1297–8.10.1002/pd.4226Search in Google Scholar PubMed

21. Alldred SK, Deeks JJ, Guo B, Neilson JP, Alfirevic Z. Second trimester serum tests for Down’s syndrome screening. Cochrane Database Syst Rev 2012;CD009925, DOI: 10.1002/14651858.10.1002/14651858Search in Google Scholar

22. Coelingh Bennink F, Holinka CF, Visser M, Coelingh Bennink HJ. Maternal and fetal estetrol levels during pregnancy. Climacteric 2008;11(Suppl 1):69–72.10.1080/13697130802056321Search in Google Scholar PubMed

23. Gurpide E, Schwers J, Welch MT, Vande Wiele RL, Lieberman S. Fetal and maternal metabolism of estradiol during pregnancy. J Clin Endocrinol Metab 1966;26:1355–65.10.1210/jcem-26-12-1355Search in Google Scholar PubMed

24. Hagen AA, Barr M, Diczfalusy E. Metabolism of 17-beta-oestradiol-4–14-C in early infancy. Acta Endocrinol (Copenh) 1965;49:207–20.10.1530/acta.0.0490207Search in Google Scholar

25. Schwers J, Eriksson G, Diczfalusy E. 15Alpha-hydroxylation: A new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta 1965;100:313–6.10.1016/0304-4165(65)90464-2Search in Google Scholar

26. Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig 2012;9:95–103.10.1515/hmbci-2012-0015Search in Google Scholar PubMed

27. Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valera MC, Gompel A, Gerard C, Pequeux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, Arnal JF. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med 2014;6:1328–46.10.15252/emmm.201404112Search in Google Scholar PubMed PubMed Central

28. Gerard C, Blacher S, Communal L, Courtin A, Tskitishvili E, Mestdagt M, Munaut C, Noel A, Gompel A, Pequeux C, Foidart JM. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation. J Endocrinol 2015;224:85–95.10.1530/JOE-14-0549Search in Google Scholar PubMed

29. Rhinehart EM. Mechanisms linking energy balance and reproduction: impact of prenatal environment. Horm Mol Biol Clin Investig 2016;25:29–43.10.1515/hmbci-2016-0004Search in Google Scholar PubMed

30. Hu XL, Feng C, Lin XH, Zhong ZX, Zhu YM, Lv PP, Lv M, Meng Y, Zhang D, Lu XE, Jin F, Sheng JZ, Xu J, Huang HF. High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth. J Clin Endocrinol Metab 2014;99:2217–24.10.1210/jc.2013-3362Search in Google Scholar PubMed

31. Mouzon SH, Lassance L. Endocrine and metabolic adaptations to pregnancy; impact of obesity. Horm Mol Biol Clin Investig 2015;24:65–72.10.1515/hmbci-2015-0042Search in Google Scholar PubMed

32. Aydin HI, Eser A, Kaygusuz I, Yildirim S, Celik T, Gunduz S, Kalman S. Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers. J Perinat Med 2016;44:669–76.10.1515/jpm-2014-0353Search in Google Scholar PubMed

33. Ahlgren M, Wohlfahrt J, Olsen LW, Sorensen TI, Melbye M. Birth weight and risk of cancer. Cancer 2007;110:412–9.10.1002/cncr.22773Search in Google Scholar PubMed

34. Barker DJ, Martyn CN, Osmond C, Hales CN, Fall CH. Growth in utero and serum cholesterol concentrations in adult life. Br Med J 1993;307:1524–7.10.1136/bmj.307.6918.1524Search in Google Scholar PubMed PubMed Central

35. Martyn CN, Barker DJ, Jespersen S, Greenwald S, Osmond C, Berry C. Growth in utero, adult blood pressure, and arterial compliance. Br Heart J 1995;73:116–21.10.1136/hrt.73.2.116Search in Google Scholar PubMed PubMed Central

36. Fowden AL, Forhead AJ. Glucocorticoids as regulatory signals during intrauterine development. Exp Physiol 2015;100: 1477–87.10.1113/EP085212Search in Google Scholar PubMed

37. Bolt RJ, van Weissenbruch MM, Lafeber HN, Delemarre-van de Waal HA. Glucocorticoids and lung development in the fetus and preterm infant. Pediatr Pulmonol 2001;32:76–91.10.1002/ppul.1092Search in Google Scholar PubMed

38. McKinlay CJ, Dalziel SR, Harding JE. Antenatal glucocorticoids: where are we after forty years? J Dev Orig Health Dis 2015;6: 127–42.10.1017/S2040174414000579Search in Google Scholar PubMed

39. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;CD004454.10.1002/14651858.CD004454.pub2Search in Google Scholar PubMed

40. Painter RC, Roseboom TJ, de Rooij SR. Long-term effects of prenatal stress and glucocorticoid exposure. Birth Defects Res C Embryo Today 2012;96:315–24.10.1002/bdrc.21021Search in Google Scholar PubMed

41. Murphy VE, Smith R, Giles WB, Clifton VL. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr Rev 2006;27:141–69.10.1210/er.2005-0011Search in Google Scholar PubMed

42. Stirrat LI, O’Reilly JR, Riley SC, Howie AF, Beckett GJ, Smith R, Walker BR, Norman JE, Reynolds RM. Altered maternal hypothalamic-pituitary-adrenal axis activity in obese pregnancy is associated with macrosomia and prolonged pregnancy. Pregnancy Hypertens 2014;4:238.10.1016/j.preghy.2014.03.028Search in Google Scholar PubMed

43. Stirrat LI, O’Reilly JR, Barr SM, Andrew R, Riley SC, Howie AF, Bowman M, Smith R, Lewis JG, Denison FC, Forbes S, Seckl JR, Walker BR, Norman JE, Reynolds RM. Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: associations with birthweight and gestation at delivery. Psychoneuroendocrinology 2016;63:135–43.10.1016/j.psyneuen.2015.09.019Search in Google Scholar PubMed

44. Nawathe AR, Christian M, Kim SH, Johnson M, Savvidou MD, Terzidou V. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clin Epigenetics 2016;8:11.10.1186/s13148-016-0178-5Search in Google Scholar PubMed PubMed Central

45. Lagiou P, Samoli E, Hsieh CC, Lagiou A, Xu B, Yu GP, Onoyama S, Chie L, Adami HO, Vatten LJ, Trichopoulos D, Williams MA. Maternal and cord blood hormones in relation to birth size. Eur J Epidemiol 2014;29:343–51.10.1007/s10654-014-9914-3Search in Google Scholar PubMed

46. Fowden AL, Forhead AJ. Endocrine regulation of feto-placental growth. Horm Res 2009;72:257–65.10.1159/000245927Search in Google Scholar PubMed

47. McDonald EA, Wolfe MW. Adiponectin attenuation of endocrine function within human term trophoblast cells. Endocrinology 2009;150:4358–65.10.1210/en.2009-0058Search in Google Scholar PubMed

48. Barbour LA, Shao J, Qiao L, Pulawa LK, Jensen DR, Bartke A, Garrity M, Draznin B, Friedman JE. Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol 2002;186:512–7.10.1067/mob.2002.121256Search in Google Scholar PubMed

49. McIntyre HD, Serek R, Crane DI, Veveris-Lowe T, Parry A, Johnson S, Leung KC, Ho KK, Bougoussa M, Hennen G, Igout A, Chan FY, Cowley D, Cotterill A, Barnard R. Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth. J Clin Endocrinol Metab 2000;85:1143–50.10.1210/jcem.85.3.6480Search in Google Scholar

50. Dos Santos E, Duval F, Vialard F, Dieudonne MN. The roles of leptin and adiponectin at the fetal-maternal interface in humans. Horm Mol Biol Clin Investig 2015;24:47–63.10.1515/hmbci-2015-0031Search in Google Scholar PubMed

51. Sooranna SR, Ward S, Bajoria R. Fetal leptin influences birth weight in twins with discordant growth. Pediatr Res 2001;49:667–72.10.1203/00006450-200105000-00010Search in Google Scholar PubMed

52. Forhead AJ, Fowden AL. The hungry fetus? Role of leptin as a nutritional signal before birth. J Physiol 2009;587:1145–52.10.1113/jphysiol.2008.167072Search in Google Scholar PubMed PubMed Central

53. Karowicz-Bilinska A. [Leptin concentration in women with normal pregnancy and intrauterine growth retardation]. Ginekol Pol 2004;75:10–4.Search in Google Scholar

54. Ibanez L, Sebastiani G, Lopez-Bermejo A, Diaz M, Gomez-Roig MD, de Zegher F. Gender specificity of body adiposity and circulating adiponectin, visfatin, insulin, and insulin growth factor-I at term birth: relation to prenatal growth. J Clin Endocrinol Metab 2008;93:2774–8.10.1210/jc.2008-0526Search in Google Scholar PubMed

55. Haghiac M, Basu S, Presley L, Serre D, Catalano PM, Hauguel-de Mouzon S. Patterns of adiponectin expression in term pregnancy: impact of obesity. J Clin Endocrinol Metab 2014;99:3427–34.10.1210/jc.2013-4074Search in Google Scholar PubMed PubMed Central

56. Palin MF, Bordignon VV, Murphy BD. Adiponectin and the control of female reproductive functions. Vitam Horm 2012;90: 239–87.10.1016/B978-0-12-398313-8.00010-5Search in Google Scholar

57. Duval F, Santos ED, Poidatz D, Serazin V, Gronier H, Vialard F, Dieudonne MN. Adiponectin inhibits nutrient transporters and promotes apoptosis in human villous cytotrophoblasts: involvement in the control of fetal growth. Biol Reprod 2016;94:111.10.1095/biolreprod.115.134544Search in Google Scholar

58. Pasqualini JR, Kincl FA, Sumida C. Receptors, mechanism of action and biological responses in the fetal, placental and maternal compartments. In: Pasqualini JR, Kincl FA, editors. Hormones and the fetus, vol. 2. Oxford: Pergamon Press, 1991:51–264.10.1016/B978-0-08-035720-1.50006-2Search in Google Scholar

59. Brandenberger AW, Tee MK, Lee JY, Chao V, Jaffe RB. Tissue distribution of estrogen receptors alpha (ER-alpha) and beta (ER-beta) mRNA in the midgestational human fetus. J Clin Endocrinol Metab 1997;82:3509–12.10.1210/jcem.82.10.4400Search in Google Scholar

60. Takeyama J, Suzuki T, Inoue S, Kaneko C, Nagura H, Harada N, Sasano H. Expression and cellular localization of estrogen receptors alpha and beta in the human fetus. J Clin Endocrinol Metab 2001;86:2258–62.10.1210/jcem.86.5.7447Search in Google Scholar

61. Sumida C, Pasqualini JR. Antiestrogens antagonize the stimulatory effect of epidermal growth factor on the induction of progesterone receptor in fetal uterine cells in culture. Endocrinology 1989;124:591–7.10.1210/endo-124-2-591Search in Google Scholar

62. Pasqualini JR. Growth factors during fetal life. In: Pasqualini JR, Scholler R, editors. Hormones and fetal pathophysiology. New York: Marcel Dekker, 1992:673–714.Search in Google Scholar

63. Allffrey VG. Molecular aspects of the regulation of eukaryotic transcription: nucleosomal proteins and their postsynthetic modifications in the control of DNA conformation and template function. In: Goldstein L, Prescott DM, editors. Cell biology, vol. 3. New York, London: Academic Press, 1980:347–437.10.1016/B978-0-12-289503-6.50015-1Search in Google Scholar

64. Pasqualini JR, Cosquer-Clavreul C, Vidali G, Allfrey VG. Effects of estradiol on the acetylation of histones in the fetal uterus of the guinea pig. Biol Reprod 1981;25:1035–9.10.1095/biolreprod25.5.1035Search in Google Scholar

65. Pasqualini JR, Sterner R, Mercat P, Allfrey VG. Estradiol enhanced acetylation of nuclear high mobility group proteins of the uterus of newborn guinea pigs. Biochem Biophys Res Commun 1989;161:1260–6.10.1016/0006-291X(89)91378-8Search in Google Scholar

66. Hendzel MJ, Kruhlak MJ, MacLean NA, Boisvert F, Lever MA, Bazett-Jones DP. Compartmentalization of regulatory proteins in the cell nucleus. J Steroid Biochem Mol Biol 2001;76:9–21.10.1016/S0960-0760(00)00153-9Search in Google Scholar

67. Shoulars K, Rodrigues MA, Crowley JR, Turk J, Thompson T, Markaverich BM. Nuclear type II [3H]estradiol binding sites: a histone H3-H4 complex. J Steroid Biochem Mol Biol 2005;96: 19–30.10.1016/j.jsbmb.2004.12.047Search in Google Scholar PubMed

68. Panchenko PE, Voisin S, Jouin M, Jouneau L, Prezelin A, Lecoutre S, Breton C, Jammes H, Junien C, Gabory A. Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice. Clin Epigenetics 2016;8:22.10.1186/s13148-016-0188-3Search in Google Scholar PubMed PubMed Central

69. Mendelson CR, Boogaram V. Hormonal and development regulation of the surfactant-associated proteins in fetal lung. In: Pasqualini JR, Scholler R, editors. Hormones and fetal pathophysiology. New York: Marcel Dekker, 1992:87–118.Search in Google Scholar

70. De Blasio MJ, Boije M, Kempster SL, Smith GC, Charnock-Jones DS, Denyer A, Hughes A, Wooding FB, Blache D, Fowden AL, Forhead AJ. Leptin matures aspects of lung structure and function in the ovine fetus. Endocrinology 2016;157:395–404.10.1210/en.2015-1729Search in Google Scholar PubMed PubMed Central

71. Olver RE, Walters DV, M Wilson S. Developmental regulation of lung liquid transport. Annu Rev Physiol 2004;66:77–101.10.1146/annurev.physiol.66.071702.145229Search in Google Scholar PubMed

72. Seckl JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 2004;151(Suppl 3):U49–62.10.1530/eje.0.151u049Search in Google Scholar PubMed

73. Freemark M. Placental hormones and the control of fetal growth. J Clin Endocrinol Metab 2010;95:2054–7.10.1210/jc.2010-0517Search in Google Scholar PubMed

74. Konstantakou P, Mastorakos G, Vrachnis N, Tomlinson JW, Valsamakis G. Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond. J Matern Fetal Neonatal Med 2016, [Epub ahead of print].10.3109/14767058.2016.1171308Search in Google Scholar PubMed

75. Dy J, Guan H, Sampath-Kumar R, Richardson BS, Yang K. Placental 11beta-hydroxysteroid dehydrogenase type 2 is reduced in pregnancies complicated with idiopathic intrauterine growth restriction: evidence that this is associated with an attenuated ratio of cortisone to cortisol in the umbilical artery. Placenta 2008;29:193–200.10.1016/j.placenta.2007.10.010Search in Google Scholar PubMed

76. Kajantie E, Dunkel L, Turpeinen U, Stenman UH, Wood PJ, Nuutila M, Andersson S. Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone shuttle in small preterm infants. J Clin Endocrinol Metab 2003;88:493–500.10.1210/jc.2002-021378Search in Google Scholar PubMed

77. Wachter R, Masarik L, Burzle M, Mallik A, von Mandach U. Differential expression and activity of 11beta-hydroxysteroid dehydrogenase in human placenta and fetal membranes from pregnancies with intrauterine growth restriction. Fetal Diagn Ther 2009;25:328–35.10.1159/000235879Search in Google Scholar PubMed

78. Cottrell EC, Seckl JR. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 2009;3:19.10.3389/neuro.08.019.2009Search in Google Scholar PubMed PubMed Central

79. Schoof E, Girstl M, Frobenius W, Kirschbaum M, Dorr HG, Rascher W, Dotsch J. Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia. J Clin Endocrinol Metab 2001;86:1313–7.10.1210/jcem.86.3.7311Search in Google Scholar

80. Chetrite GS, Cortes-Prieto J, Pasqualini JR. Effect of tibolone and its principal metabolites (3alpha- and 3beta-hydroxy, 3alpha-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue. Horm Mol Biol Clin Investig 2011;8:491–8.10.1515/HMBCI.2011.121Search in Google Scholar

81. Pasqualini JR. The selective estrogen enzyme modulators in breast cancer: a review. Biochim Biophys Acta 2004;1654:123–43.10.1016/j.bbcan.2004.03.001Search in Google Scholar PubMed

82. Pasqualini JR, Chetrite GS. Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications. Horm Mol Biol Clin Investig 2012;9:25–63.10.1515/hmbci-2012-0018Search in Google Scholar PubMed

83. Chetrite GS, Pasqualini JR. Inhibition of aromatase activity in MCF-7aro human breast cancer cells by the natural androgens testosterone and androstenedione. Horm Mol Biol Clin Investig 2010;1:147–53.10.1515/hmbci.2010.014Search in Google Scholar

84. Chetrite GS, Pasqualini JR. Nomegestrol acetate is an anti-aromatase agent in human MCF-7aro breast cancer cells. Horm Mol Biol Clin Investig 2010;3:417–24.10.1515/hmbci.2010.054Search in Google Scholar

85. Pasqualini JR, Chetrite GS. Biological responses of progestogen metabolites in normal and cancerous human breast. Horm Mol Biol Clin Investig 2010;3:427–35.10.1515/hmbci.2010.066Search in Google Scholar

86. Assicot M, Contesso G, Bohuon C. Catechol-O-methyltransferase in human breast cancers. Eur J Cancer 1977;13:961–6.10.1016/0014-2964(77)90173-6Search in Google Scholar

87. Pasqualini JR, Chetrite G. The selective Estrogen Enzyme Modulators (SEEM) in breast cancer. In: Pasqualini JR, editors. Breast cancer: prognosis, treatment and prevention. New York: Marcel Dekker, 2002:187–249.10.1201/b14039-8Search in Google Scholar

88. Zhu BT, Conney AH. Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Res 1998;58:2269–77.Search in Google Scholar

89. Lippert C, Seeger H, Mueck AO. The effect of endogenous estradiol metabolites on the proliferation of human breast cancer cells. Life Sci 2003;72:877–83.10.1016/S0024-3205(02)02305-6Search in Google Scholar

90. Merriam GR, MacLusky NJ, Picard MK, Naftolin F. Comparative properties of the catechol estrogens, I: methylation by catechol-O-methyltransferase and binding to cytosol estrogen receptors. Steroids 1980;36:1–11.10.1016/0039-128X(80)90062-8Search in Google Scholar

91. Liehr JG, Fang WF, Sirbasku DA, Ari-Ulubelen A. Carcinogenicity of catechol estrogens in Syrian hamsters. J Steroid Biochem 1986;24:353–6.10.1016/0022-4731(86)90080-4Search in Google Scholar

92. Mueck AO, Seeger H, Lippert TH. Estradiol metabolism and malignant disease. Maturitas 2002;43:1–10.10.1016/S0378-5122(02)00141-XSearch in Google Scholar

93. Osborne MP, Bradlow HL, Wong GY, Telang NT. Upregulation of estradiol C16 alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J Natl Cancer Inst 1993;85:1917–20.10.1093/jnci/85.23.1917Search in Google Scholar PubMed

94. Lewis JS, Thomas TJ, Klinge CM, Gallo MA, Thomas T. Regulation of cell cycle and cyclins by 16alpha-hydroxyestrone in MCF-7 breast cancer cells. J Mol Endocrinol 2001;27: 293–307.10.1677/jme.0.0270293Search in Google Scholar PubMed

95. Pasqualini JR. Fetus, pregnancy and breast cancer. In: Pasqualini JR, editors. breast cancer: prognosis, treatment and prevention. New York: Marcel Dekker, 2002:19–71.10.1201/b14039-3Search in Google Scholar

Received: 2016-7-17
Accepted: 2016-7-26
Published Online: 2016-8-29
Published in Print: 2016-7-1

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