IMMUNOREGULATION OF BLOOD SERUM ESTRADIOL AND PROGESTERONE LEVELS IN POSTMENOPAUSAL WOMEN

Specific antibodies against estradiol (Es) and progesterone (Pg) are known to modulate blood serum concentrations of these hormones and their biological effects after immunization of animals. It was suggested that specific IgA-Es and IgA-Pg could influence on Es and Pg levels in human blood serum. The purpose of this study was to identify the suggested correlations between serum Es and Pg and specific IgA-Es and IgA-Pg in postmenopausal healthy women (HW) and breast cancer patients (BCP). The serum levels of Es, Pg, IgA-Es and IgA-Pg were studied in 226 HW and 633 BCP by means of solid-phase immunoassay. The following results were obtained. The levels of Es in BCP (0.25 nmol/l) were higher than in HW (0.16; р < 0.0001). The levels of Pg were lower (0.79 vs 0.87; р < 0.0001), and individual Pg/Es ratios were lower (3.19 vs 6.64; р < 0.0001). Individual IgA-Pg/IgA-Es ratios correlated with decrease of Es (r_s = -0.15; p = 0.029), with increase in Pg (r_s = 0.38; р < 0.0001), and with increased Pg/Es ratio (r_s = 0.29; р < 0.0001) in healthy women. Similar correlations were determined in BCP (correspondingly: r_s = -0.14, р < 0.001; r_s = 0.1, р = 0.009; r_s = 0.15, р < 0.0001). The decrease of Es and increase of Pg and Pg/Es in BCP were less significant than in HW: the a quotients in regression у = ах+b (y = hormones levels and x = antibodies levels) in BCP were 3 to 4-fold lower than in HW. These peciliarities of interrelations between hormones and specific antibody levels were revealed only in ER⁺/PR⁺ BCP but not in ER⁺/PR^- and ER^-/PR^- BCP. In conclusion, we have confirmed a suggestion about participation of specific antibodies in regulation of steroids levels in human blood serum. The immune regulation of hormonal status was weakened in BCP.

1. Gladkova K.A., Menzhinskaya I.V., Sukhikh G.T., Sidelnikova V.M. Sensitization role of progesterone in the clinical presentation of miscarriage. Problemy reproduktsii = Russian Journal of Human Reproduction, 2007, Vol. 13, no. 6, pp. 95-98. (In Russ.)

2. Glushkov A.N., Krasilnikova K.S., Polenok E.G., Kostyanko M.V., Olennikova R.V., Nersesyan S.L. Combined effect of antibodies to benzo[a]pyrene, estradiol and progesterone upon sex hormone concentrations in blood serum of pregnant women congenital malformations of fetus. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 5, pp. 647-656. (In Russ.) doi :10.15789/1563-0625-2018-5-647-656.

3. Glushkov A.N., Polenok E.G., Anosova T.P., Savchenko Ya.A., Bakanova M.L., Minina V.I., Mun S.A., Larin S.A., Kostyanko M.V. Serum antibodies to benzo[a]pyrene and chromosomal aberrations in lymphocytes peripheral blood at the workers of coal processing enterprise. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2011, Vol. 5 (14), no. 1, pp. 39-44. (In Russ.)

4. Glushkov A.N., Polenok E.G., Kostyanko M.V., Antonov A.V., Verzhbitskaya N.E., Vafin I.A., Ragozhina S.E. Antibodies and anti-antibodies to steroid hormones, and breast cancer risk. Meditsinskaya immunologiya = Medical Immunology (Russia), 2017, Vol. 19, no. 5, pp. 577-584. (In Russ.) doi: 10.15789/1563-0625-2017-5-577-584.

5. Glushkov A.N., Polenok E.G., Kostyanko M.V., Rogozin A.I., Antonov A.V., Verzhbitskaya N.E. Combination effects of antibodies to benzo[a]pyrene, estradiol and progesterone onto concentrations of female sex hormones in blood serum of the breast cancer patients risks. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2018, Vol. 12, no. 21, pp. 40-45. (In Russ.)

6. Fedotcheva Т.A., Shimahovsky N.L. Role of gestagens and antigestagens in the regulation of proliferate activity of breast cancer cells. Voprosy biologicheskoy, meditsinskoy i farmatsevticheskoy khimii = Problems of Biological, Medical and Pharmaceutical Chemistry, 2005, no. 3, pp. 3-11. (In Russ.)

7. Bochskanl R., Thie M., Kirchner C.J. Active immunization of rabbits against progesterone: increase in hormone levels, and changes in metabolic clearance rates and in genital tract tissues. J. Steroid Biochem., 1989, Vol. 33, no. 3, pp. 349-355.

8. Caldwell B.V., Tillson S.A., Esber H., Thorneycroft I.H. Survival of tumors after immunization against oestrogens. Nature, 1971, Vol. 231, no. 5298, pp. 118-119.

9. Chang C.F., Roberts A.J., Reeves J.J. Increased luteinizing hormone secretion and ovarian function in Heifers actively immunized against estrogen and progesterone J. Anim. Sci., 1987, Vol. 65, no. 3, pp. 771-776.

10. Dray F., Csapo A.I., Erdos T. Effects of antibodies to estradiol 17 beta and to progesterone on the placental weight and pregnancy in rats – a quantitative study. J. Steroid Biochem., 1975, Vol. 6, no. 3-4, pp. 547-548.

11. Elsaesser F. Effects of active immunization against oestradiol-17 beta, testosterone or progesterone on receptivity in the female rabbit and evaluation of specificity. J. Reprod. Fertil., 1980, Vol. 58, no. 1, pp. 213-218.

12. Fernandez S.V., Russo I.H., Russo J. Estradiol and its metabolites 4-hydroxyestradiol and 2-hydroxyestradiol induce mutations in human breast epithelial cells. Int. J. Cancer., 2006, Vol. 118, no. 8, pp. 1862-1868.

13. French L.R., Spennetta B. Effects of antibodies to progesterone on reproduction of ewes. Theriogenology, 1981, Vol. 16, no. 4, pp. 407-418.

14. García-Ortega P., Scorza E. Progesterone autoimmune dermatitis with positive autologous serum skin test result. Obstet. Gynecol., 2011, Vol. 117, no. 2, Pt 2, pp. 495-498.

15. Itsekson A.M., Seidman D.S., Zolti M., Alesker M., Carp H.J. Steroid hormone hypersensitivity: Clinical presentation and management. Fertil. Steril., 2011, Vol. 95, no. 8, pp. 2571-2573.

16. Itsekson A.M., Seidman D.S., Zolti M., Lazarov A., Carp H.J. Recurrent pregnancy loss and inappropriate local immune response to sex hormones. Am. J. Reprod. Immunol., 2007, Vol. 57, no. 2, pp. 160-165.

17. Kaushansky A., Bauminger S., Koch Y., Lindner H.R., Endocrine and reproductive repercussions of immunization against progesterone and oestradiol in female rats. Acta Endocrinol. (Copenh), 1977, Vol. 84, no. 4, pp. 795-803.

18. Kim J.Y., Han W., Moon H.G., Ahn S.K., Kim J., Lee J.W., Kim M.K., Kim T., Noh D.Y. Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer. BMC Cancer, 2013, Vol. 13, p. 503.

19. Martin T.E., Henricks D.M., Hill J.R. Jr, Rawlings N.C. Active immunization of the cow against oestradiol-17beta. J. Reprod. Fertil., 1978, Vol. 53, no. 1, pp. 173-178.

20. Rawlings N.C., Kennedy S.W., Henricks D.M. The active immunization of the cyclic ewe against an estrone protein conjugates. Theriogenology, 1979, Vol. 12, no. 3, pp. 139-151.

21. Roby R.R., Richardson R.H., Vojdani A. Hormone allergy. Am. J. Reprod. Immunol., 2006, Vol. 55, no. 4, pp. 307-313.

22. Sundaram K., Tsong Y.Y., Hood W., Brinson A. Effect of immunization with estrone-protein conjugate in rhesus monkeys. Endocrinology, 1973, Vol. 93, no. 4, pp. 843-847.

23. Thomas G.B., Oldham C.M., Hoskinson R.M., Scaramuzzi R.J., Martin G.B. Effect of immunization against progesterone on oestrus, cycle length, ovulation rate, luteal regression and LH secretion in the ewe. Aust. J. Biol. Sci., 1987, Vol. 40, no. 3, pp. 307-313.

24. Wotiz H.H., Scublinsky A., Walker C. Effect of estrogen antibodies on pregnancy in the rat. Gynecol. Invest., 1972, Vol. 3, no. 1, pp. 124-125.