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Steroid metabolome and multiple pregnancy


Authors: A. Černý 1 ;  Laštůvka Z. 1;  M. Hill 2 ;  A. Pařízek 1
Authors place of work: Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze 1;  Oddělení steroidů a proteofaktorů, Endokrinologický ústav v Praze 2
Published in the journal: Ceska Gynekol 2022; 87(3): 217-223
Category: Review Article
doi: https://doi.org/10.48095/cccg2022217

Summary

Steroid biosynthesis occurs in adrenal, gonadal, brain, liver, and placental tissues. Depending on the location of their activity, steroids can be divided into two groups – intracellular and extracellular. Intracellular ones act as transcription factors, suppressing or activating gene expression – they have a so-called genomic effect and therefore their onset of action is slow. Steroids acting extracellularly (non-genome effect) bind to neurotransmitter receptors located on the cytoplasmic cell membrane and thus affect the permeability of the ion channels, the effect of which is much faster, and we refer to them as neuroactive steroids or neurosteroids. While neuroactive steroids can be produced in different tissues of the body, or can be administered externally, neurosteroids are synthetized in cells of the nervous system. Some neuroactive steroids whose levels are extremely elevated in pregnancy (progesterone and its metabolites) are crucial in stabilizing pregnancy and changes in their concentration may influence the onset of parturition. Steroidogenic disorders may be involved in a number of pregnancy pathologies such as premature birth, pre-eclampsia, intrahepatic cholestasis in pregnancy, etc. Our research in collaboration with the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague also focuses on the investigation of multiple pregnancies in terms of biosynthesis, transport, and the effects of steroids. Studies available in the literature so far have not provided a comprehensive analysis of the steroidome in children and mothers in multiple pregnancies. The aim of our research is therefore to clarify the relationships between fetuses and mothers and between fetuses from the point of view of steroid synthesis and transport as well as the physiology and pathophysiology of human pregnancy and childbirth.

Keywords:

multiple pregnancy – fetomaternal steroidome – neuroactive steroids – pregnancy complication


Zdroje

1. Strauss JF, Barbieri RB. Yen & Jaffe’s reproductive endocrinology physiology, pathophysiology, and clinical management. 8th ed. Philadelphia: Elsevier 2019: 367.

2. Rupprecht R, Reul JM, Trapp T et al. Progesterone receptor-mediated effects of neuroactive steroids. Neuron 1993; 11(3): 523–530. doi: 10.1016/ 0896-6273(93)90156-I.

3. Tuem KB, Atey TM. Neuroactive steroids: receptor interactions and responses. Front Neurol 2017; 8: 442. doi: 10.3389/ fneur.2017.00442.

4. Mitchell BF, Mitchell JM, Chowdhury J et al. Metabolites of progesterone and the pregnane X receptor: a novel pathway regulating ute rine contractility in pregnancy? Am J Obstet Gynecol 2005; 192(4): 1304–1315. doi: 10.1016/ j. ajog.2005.01.040.

5. Pasqualini JR, Chetrite GS. The formation and transformation of hormones in maternal, placental and fetal compartments: bio logical implications. Horm Mol Biol Clin Investig 2016; 27(1): 11–28. doi: 10.1515/ hmbci-2016-0036.

6. Hill M, Parizek A, Cibula D et al. Steroid metabolome in fetal and maternal body fluids in human late pregnancy. J Steroid Biochem Mol Biol 2010; 122(4): 114–132. doi: 10.1016/ j. jsbmb.2010.05.007.

7. Krone N, Hughes BA, Lavery GG et al. Gas chromatography/ mass spectrometry (GC/ MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/ MS/ MS). J Steroid Biochem Mol Biol 2010; 121(3–5): 496–504. doi: 10.1016/ j. jsbmb.2010.04.010.

8. Haneef J, Shaharyar M, Husain A et al. Application of LC–MS/ MS for quantitative analysis of glucocorticoids and stimulants in bio logical fluids. J Pharm Anal 2013; 3(5): 341–348. doi: 10.1016/ j.jpha.2013.03.005.

9. Marcos J, Renau N, Casals G et al. Investigation of endogenous corticosteroids profi les in human urine based on liquid chromatography tandem mass spectrometry. Anal Chim Acta 2014; 812: 92–104. doi: 10.1016/ j.aca.2013.12.030.

10. Dušková M, Kolátorová L, Šimková M et al. Steroid diagnostics of 21st century in the light of their new roles and analytical tools. Physiol Res 2020; 69(Suppl 2): S193–S203. doi: 10.33549/ physiolres.934517.

11. Yuan TF, Le J, Wang ST et al. An LC/ MS/ MS method for analyzing the steroid metabolome with high accuracy and from small serum samples. J Lipid Res 2020; 61(4): 580–586. doi: 10.1194/ jlr.D119000591.

12. Hill M, Hána V Jr, Velíková M et al. A method for determination of one hundred endogenous steroids in human serum by gas chromatography – tandem mass spectrometry. Physiol Res 2019; 68(2): 179–207. doi: 10.33549/ physiolres. 934124.

13. Pašková A. Úloha neuroaktivních steroidů v těhotenství a jejich význam v prenatální diagnostice. Disertační práce. Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze 2013.

14. Adamcová K, Kolátorová L, Škodová T et al. Steroid hormone levels in the peripartum period – differences caused by fetal sex and deli very type. Physiol Res 2018; 67(Suppl 3): S489–S497. doi: 10.33549/ physiolres.934019.

15. Ellis MJ, Livesey JH, Inder WJ et al. Plasma corticotropin-releasing hormone and unconjugated estriol in human pregnancy: gestational patterns and ability to predict preterm delivery. Am J Obstet Gynecol 2002; 186(1): 94–99. doi: 10.1067/ mob.2002.119188.

16. Hill M, Parizek A, Kancheva R et al. Steroid metabolome in plasma from the umbilical artery, umbilical vein, maternal cubital vein and in amniotic fluid in normal and preterm labor. J Steroid Biochem Mol Biol 2010; 121(3–5): 594– 610. doi: 10.1016/ j.jsbmb.2009.10.012.

17. McLean M, Smith R. Corticotrophin-releasing hormone and human parturition. Reproduction 2001; 121(4): 493–501. doi: 10.1530/ rep. 0.1210493.

18. Ravanos K, Dagklis T, Petousis S et al. Factors implicated in the initiation of human parturition in term and preterm labor: a review. Gynecol Endocrinol 2015; 31(9): 679–683. doi: 10.3109/ 09513590.2015.1076783.

19. Linton EA, Woodman JR, Asboth G et al. Corticotrophin releasing hormone: its potential for a role in human myometrium. Exp Physiol 2001; 86(2): 273–281. doi: 10.1113/ eph8602183.

20. Grammatopoulos D, Thompson S, Hillhouse EW. The human myometrium expresses multiple isoforms of the corticotropin-releasing hormone receptor. J Clin Endocrinol Metab 1995; 80(8): 2388–2393. doi: 10.1210/ jcem.80.8.7629235.

21. Zhu P, Tao FB, Jiang XM et al. Effect of intrahepatic cholestasis of pregnancy on the functions of hypothalamic-pituitary-adrenocortical axis and adrenal cortex in normal neonates. Zhongguo Dang Dai Er Ke Za Zhi 2010; 12(1): 5–8.

22. Pařízek A, Dušková M, Vítek L et al. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy. Physiol Res 2015; 64(Suppl 2): S203–S209. doi: 10.33549/ physiolres.933117.

23. Pařízek A, Hill M, Dušková M et al. A comprehensive evaluation of steroid metabolism in women with intrahepatic cholestasis of pregnancy. PLoS One 2016; 11(8): e0159203. doi: 10.1371/ journal.pone.0159203.

24. Šimják P, Pařízek A, Vítek L et al. Fetal complications due to intrahepatic cholestasis of pregnancy. J Perinat Med 2015; 43(2): 133–139. doi: 10.1515/ jpm-2014-0089.

25. Parker CR Jr, Everett RB, Quirk JG Jr et al. Hormone production during pregnancy in the primigravid patient. I. Plasma levels of progesterone and 5-alpha-pregnane-3,20-dione throughout pregnancy of normal women and women who developed pregnancy-induced hypertension. Am J Obstet Gynecol 1979; 135(6): 778–782.

26. Luisi S, Petraglia F, Benedetto C et al. Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients. J Clin Endocrinol Metab 2000; 85(7): 2429–2433. doi: 10.1210/ jcem.85.7.6675.

27. Berkane N, Liere P, Oudinet JP et al. From pregnancy to preeclampsia: a key role for estrogens. Endocr Rev 2017; 38(2): 123–144. doi: 10.1210/ er.2016-1065.

28. Baud O, Berkane N. Hormonal changes associated with intra-uterine growth restriction: impact on the developing brain and future neurodevelopment. Front Endocrinol (Lausanne) 2019; 10: 179. doi: 10.3389/ fendo.2019.00 179.

29. Hirst JJ, Kelleher MA, Walker DW et al. Neuroactive steroids in pregnancy: key regulatory and protective roles in the foetal brain. J Steroid Biochem Mol Biol 2014; 139: 144–153. doi: 10.1016/ j.jsbmb.2013.04.002.

30. Hirst JJ, Palliser HK, Yates DM et al. Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies. Neurochem Int 2008; 52(4–5): 602–610. doi: 10.1016/ j.neuint.2007.07.018.

31. Hirst JJ, Yawno T, Nguyen P et al. Stress in pregnancy activates neurosteroid production in the fetal brain. Neuroendocrinology 2006; 84(4): 264–274. doi: 10.1159/ 000097990.

32. Deligiannidis KM, Kroll-Desrosiers AR, Mo S et al. Peripartum neuroactive steroid and -ami nobutyric acid profiles in women at-risk for postpartum depression. Psychoneuroendocrinology 2016; 70: 98–107. doi: 10.1016/ j. psyneuen.2016.05.010.

33. McEvoy K, Payne JL, Osborne LM. Neuroactive steroids and perinatal depression: a review of recent literature. Curr Psychiatry Rep 2018; 20(9): 78. doi: 10.1007/ s11920-018-09 37-4.

34. Hellgren C, Comasco E, Skalkidou A et al. Allopregnanolone levels and depressive symptoms during pregnancy in relation to single nucleotide polymorphisms in the allopregnanolone synthesis pathway. Horm Behav 2017; 94: 106–113. doi: 10.1016/ j.yhbeh.2017.06. 008.

35. Todorovic SM, Pathirathna S, Brimelow BC et al. 5beta-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2+ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo. Mol Pharmacol 2004; 66(5): 1223–1235. doi: 10.1124/ mol.104.002402.

36. Zorumski CF, Paul SM, Covey DF et al. Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond. Neurobio l Stress 2019; 11: 100196. doi: 10.1016/ j. ynstr.2019.100196.

37. Belelli D, Hogenkamp D, Gee KW et al. Reali sing the therapeutic potential of neuroactive steroid modulators of the GABAA receptor. Neurobio l Stress 2019; 12: 100207. doi: 10.1016/ j.ynstr.2019.100207.

38. Anker JJ, Carroll ME. The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research. Neurosci Biobehav Rev 2010; 35(2): 315–333. doi: 10.1016/ j.neubio rev.2010.04. 003.

39. Good clinical practice network. Studie brexanolonu pro akutní syndrom respirační tísně v důsledku covid-19. 2021 [online]. Available from: https:/ / ichgcp.net/ cs/ clinical-trials-registry/ NCT04 537806.

40. Shaw JC, Dyson RM, Palliser HK et al. Neurosteroid replacement therapy using the allopregnanolone- analogue ganaxolone following preterm birth in male guinea pigs. Pediatr Res 2019; 85(1): 86–96. doi: 10.1038/ s41390-018-01 85-7.

41. Karasu T, Marczylo TH, Maccarrone M et al. The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility. Hum Reprod Update 2011; 17(3): 347–361. doi: 10.1093/ humupd/ dmq058.

42. Santoro A, Mele E, Marino M et al. The complex interplay between endocannabinoid system and the estrogen system in central nervous system and periphery. Int J Mol Sci 2021; 22(2): 972. doi: 10.3390/ ijms22020 972.

43. Chauhan SP, Scardo JA, Hayes E et al. Twins: prevalence, problems, and preterm births. Am J Obstet Gynecol 2010; 203(4): 305–315. doi: 10.1016/ j.ajog.2010.04.031.

44. Sentilhes L, Oppenheimer A, Bouhours AC et al. Neonatal outcome of very preterm twins: policy of planned vaginal or cesarean delivery. Am J Obstet Gynecol 2015; 213(1): 73.e1–73.e7. doi: 10.1016/ j.ajog.2015.02.020.

45. Townsend R, Khalil A. Fetal growth restriction in twins. Best Pract Res Clin Obstet Gynaecol 2018; 49: 79–88. doi: 10.1016/ j.bpobgyn.2018.02.004.

46. Bamberg C, Hecher K. Update on twin-to-twin transfusion syndrome. Best Pract Res Clin Obstet Gynaecol 2019; 58: 55–65. doi: 10.1016/ j.bpobgyn.2018.12.011.

47. Canpolat FE, Yurdakök M, Korkmaz A et al. Birthweight discordance in twins and the risk of being heavier for respiratory distress syndrome. Twin Res Hum Genet 2006; 9(5): 659–663. doi: 10.1375/ 183242706778553372.

48. Tapp AL, Maybery MT, Whitehouse AJ. Evaluating the twin testosterone transfer hypothesis: a review of the empirical evidence. Horm Behav 2011; 60(5): 713–722. doi: 10.1016/ j.yhbeh.2011.08.011.

49. Cohen-Bendahan CC, van Goozen SH, Buitelaar JK et al. Maternal serum steroid levels are unrelated to fetal sex: a study in twin pregnancies. Twin Res Hum Genet 2005; 8(2): 173–177. doi: 10.1375/ 1832427053738764.

50. Talia C, Raja EA, Bhattacharya S et al. Testing the twin testosterone transfer hypothesis-intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland. Hum Reprod 2020; 35(7): 1702–1710. doi: 10.1093/ humrep/ deaa091.

51. Kuijper EA, Twisk JW, Korsen T et al. Midpregnancy, perinatal, and neonatal reproductive endocrinology: a prospective cohort study in twins and singleton control subjects. Fertil Steril 2015; 104(6): 1527–1534. doi: 10.1016/ j. fertnstert.2015.08.016.

52. Thomas HV, Murphy MF, Key TJ et al. Pregnancy and menstrual hormone levels in mothers of twins compared to mothers of singletons. Ann Hum Biol 1998; 25(1): 69–75. doi: 10.1080/ 03014469800005432.

53. Pašková A, Pařízek A, Hill M et al. Steroid metabolome in the umbilical cord: is it necessary to differentiate between arterial and venous blood? Physiol Res 2014; 63(1): 115–126. doi: 10.33549/ physiolres.932624.

54. Doporučený postup České gynekologicko- porodnické společnosti. Vedení porodu vícečetného těhotenství. 2013 [online]. Dostupné z: https:/ / www.lekaridnes.cz/ wp-content/ uploads/ 2016/ 08/ p-2013-vedeni-poroduvicecetneho- tehotenstvi.pdf.

Štítky
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine

Článok vyšiel v časopise

Czech Gynaecology

Číslo 3

2022 Číslo 3
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