Progesterone neuroactive metabolites in human pregnancy

Česká verzia

Authors: M. Klímková ¹; A. Pařízek ¹; M. Velíková ³; M. Hill ²; A. Pašková ¹; Z. Žižka ¹; R. Kancheva ³; M. Kalousová ³; M. Koucký ¹; A. Germanová ¹; Z. Hájek ¹; L. Stárka ³
Authors place of work: Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha, přednosta prof. MUDr. A. Martan, DrSc. ¹; Endokrinologický ústav, Praha, ředitel doc. MUDr. V. Hainer, CSc. ²; Ústav klinické biochemie a laboratorní diagnostiky, 1. LF UK a VFN, Praha, přednosta prof. MUDr. T. Zima, DrSc., MBA ³
Published in the journal: Ceska Gynekol 2010; 75(1): 9-15

Summary

Objective:
Review of the physiological role of neuroactive and neuroprotective steroids in human pregnancy.

Design:
A review article.

Setting:
Gynecological-Obstetrical Clinic, 1^st Medical Facult, Charles University and General Hospital, Prague.

Conclusion:
Human parturition is a multi-factorial process. Various mechanisms related to the onset of labor were suggested. Estrogens show accelerating increase in late pregnancy, which probably reflect the increasing activity of fetal zone of the fetal adrenal. This zone is stimulated by progressive increase of placental CRH resulting in excessive production of conjugated 3β-hydroxy-5-en-steroids, which are transported by circulation to placenta and further metabolized to active hormones. Some progesterone metabolites probably participate in pregnancy sustaining via modulation of ligand-gated ion channels in the CNS and periphery. In this review, the question was addressed whether the catabolism of pregnancy sustaining progesterone metabolites accelerate like the estrogen formation.

Key words:
neuroactive steroids, initiation of parturition, pregnancy.

Zdroje

1. Angioni, S., Petralgia, F., Gallinelli, A., et al. Corticotropin-releasing hormone modulates cytokines release in cultured human peripheral blood mononuclear cells. Life Sci,1993, 53, p. 1735-1742.

2. Backstrom, T., Mattsson, B. Correlation of symptoms in pre-menstrual tension to oestrogen and progesterone concentrations in blood plasma. A preliminary study. Neuropsychobiology, 1975, 1, p. 80-86.

3. Corpechot, C., Leclerc, P., Baulieu, E., et al. Neurosteroids: regulatory mechanisms in male rat brain during heterosexual exposure. Steroids, 1985, p. 229-234.

4. Corpechot, C., Robel, P., Axelson, M., et al. Characterization and measurement of dehydroepiandrosterone sulfate in rat brain. Proc Natl Acad Sci USA, 1981, 78, p. 4704-4707.

5. Dombroski, RA., Casey, ML., Macdonald, PC. 5-alpha-dihydroprogesterone formation in human placenta from 5alpha-pregnan-3beta/alpha-ol-20-ones and 5-pregnan-3beta-yl-20-one sulfate. J Steroid Biochem Mol Biol, 1997, 63, p. 155-163.

6. Genazzani, AR., Petraglia, F., Bernardi, F., et al. Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab, 1998, 83, p. 2099-2103.

7. Gilbert Evans, SE., Ross, LE., Sellers, EM., et al. 3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period. Gynecol Endocrinol, 2005, 21, p. 268-279.

8. Harrison, NL., Simmonds, MA. Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res, 1984, 323, p. 287-292.

9. Hercz, P. Quantitative changes in steroid and peptide hormones in the maternal-fetoplacental system between the 28th-40th weeks of pregnancy. Acta Med Hung, 1985, 42, p. 29-39.

10. Hill, M., Bicikova, M., Parizek, A., et al. Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers. J Steroid Biochem Mol Biol, 2001, 78, p. 51-57.

11. Hill, M., Parizek, A., Bicikova, M., et al. Neuroactive steroids, their precursors, and polar conjugates during parturition and postpartum in maternal and umbilical blood: 1. Identification and simultaneous determination of pregnanolone isomers. J Steroid Biochem Mol Biol, 2000, 75, p. 237-244 .

12. Hill, M., Popov, P., Havlikova, H., et al. Altered profiles of serum neuroactive steroids in premenopausal women treated for alcohol addiction. Steroids, 2005, 70, p. 515-524.

13. Jones, SA., Challis, JR. Local stimulation of prostaglandin production by corticotropin-releasing hormone in human fetal membranes and placenta. Biochem Biophys Res Commun, 1989, 159, p. 192-199.

14. Kawahara, FS., Berman, ML., Green, OC. Conversion of progesterone-1,2-3-H to 5beta-pregnane-3,20-dione by brain tissue. Steroids, 1975, 25, p. 459-463.

15. Le Goascogne, C., Robel, P., Gouezou, M., et al. Neurosteroids: cytochrome P-450 scc in rat brain. Science, 1987, 237, p. 1212-1215.

16. Lisboa, BP., Holtermann, M. Metabolism of 20beta-hydroxy-4-pregnen-3-one in uterine tissue of non-pregnant rats in vitro. Acta Endocrinol (Copenh), 1976, 83, p. 604-620.

17. Majewska, MD., Bisserbe, JC., Eskay, RL. Glucocorticoids are modulators of GABA receptors in brain. Brain Res, 1985, 339, p. 178-182.

18. Majewska, MD., Vaupel, DB. Steroid control of uterine motility via gamma-aminobutyric acidA receptors in the rabbit: a novel mechanism? J Endocrinol, 1991, 131, p. 427-434.

19. Mclean, M., Smith, R. Corticotrophin-releasing hormone and human parturition. Reproduction, 2001, 121, p. 493-501.

20. Mesiano, S., Chan, EC., Fitter, JT., et al. Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metab, 2002, 87, p. 2924-2930.

21. Milewich, L., Gant, NF., Schwarz, BE., et al. Initiation of human parturition. IX. Progesterone metabolism by placentas of early and late human gestation. Obstet Gynecol, 1978, 51, p. 278-280.

22. Mitchell, BF., Mitchell, JM.,Chowdhury, J., et al. Metabolites of progesterone and the pregnane X receptor: a novel pathway regulating uterine contractility in pregnancy? Am J Obstet Gynecol, 2005, 192, p. 1304-1313, discussion 1313-1315.

23. Nappi, C., Meo, R., Di Carlo, C., et al. Reduced fertility and neuroendocrine dysfunction in women with epilepsy. Gynecol Endocrinol, 1994, 8, p. 133-145.

24. Ottander, U., Poromaa, IS., Bjurulf, E., et al. Allopregnanolone and pregnanolone are produced by the human corpus luteum. Mol Cel Endocrinol, 2005, 239, p. 37-44.

25. Parizek, A., Hill, M., Kancheva, M., et al. Neuroactive pregnanolone isomers during pregnancy. J Clin Endocrinol Metab, 2005, 90, p. 395-403.

26. Pearson Murphy, BE., Allison, CM. Determination of progesterone and some of its neuroactive ring A-reduced metabolites in human serum. J Steroid Biochem Mol Biol, 2000, 74, p. 137-142.

27. Petraglia, F., Florio, P., Nappi, C., et al. Peptide signaling in human placenta and membranes: autocrine, paracrine, and endocrine mechanisms. Endocr Rev, 1996, 17, p. 156-186.

28. Putnam, CD., Brann, DW., Kolbeck, RC., et al. Inhibition of uterine contractility by progesterone and progesterone metabolites: mediation by progesterone and gamma amino butyric acidA receptor systems. Biol Reprod, 1991, 45, p. 266-272.

29. Saitoh, H., Hirato, K., Tahara, R., et al. Enhancement of human amniotic phospholipase A2 activity by steroid-sulphate derived from the foeto-placental unit. Acta Endocrinol (Copenh), 1984, 107, p. 420-424.

30. Sheehan, PM., Rice, GE., Moses, EK., et al. 5beta-dihydroprogesterone and steroid 5 beta-reductase decrease in association with human parturition at term. Mol Hum Reprod, 2005, 11, p. 495-501.

31. Schreiber, V. Neuropeptides and neurosteroids. Čas Lék čes, 1980, 119, p.656-659.

32. Schumacher, M., Akwa, Y., Guennoun, R., et al. Steroid synthesis and metabolism in the nervous system: trophic and protective effects. J Neurocytol, 2000, 29, p. 307-326.

33. Schumacher, M., Weill-Engerer, S., Liere, P., et al. Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol, 2003, 71, p. 3-29.

34. Sirrianni, R., Mayhew, BA., Carr, BR., et al. Corticotropin-releasing hormone (CRH) and urocortin act through type 1 CRH receptors to stimulate dehydroepiandrosterone sulfate production in human fetal adrenal cells. J Clin Endocrinol Metab, 2005, 90, p. 5393-5400.

35. Sirrianni, R., Rehman, KS., Carr, BR., et al. Corticotropin-releasing hormone directly stimulates cortisol and the cortisol biosynthetic pathway in human fetal adrenal cells. J Clin Endocrinol Metab, 2005, 90, p. 279-285.