{"paper_id":"7a6bc0a4-0fef-43ee-80dc-01d0ad9ba271","body_text":"Abstract\nEndometriosis is an estrogen-dependent disease affecting women during their reproductive years. An abnormal immune function and, in particular, a decreased natural killer (NK) cell activity have been found in endometriosis, suggesting a role of the immune system in the pathophysiology of the disease. We have recently evidenced a significant inverse relationship between 17-ß-estradiol plasma levels and NK cytotoxicity in endometriosis patients. In this study we have investigated the combined role of 17-ß-estradiol (E2) and prolactin (PRL) in the regulation of NK cell activity during the progression of endometriosis, by evaluating the correlation among E2, PRL., and other immunomodulating neurohormones on both the cytotoxic activity and the number of NK cells in women at different stages of endometriosis. The early stages (I/II) of endometriosis are characterized by increased plasma levels of either E2 or PRL without significant alterations of NK cell activity in comparison with healthy subjects. The progression to advanced stages (III/IV) of the disease is associated with a further increase of E2 levels, a decrease of PRL plasma concentrations (with an increase of E2/PRL ratio), and an impairment of NK cytotoxicity. The plasma levels of both E2 and PRL and the E2/PRL ratio are significantly correlated with the values of NK cytotoxicity in advanced stages of endometriosis. Either the absolute number or the relative percentage of CD16+ or CD56+ peripheral lymphocytes are not significantly different between patients at either stages I/II or III/IV and healthy controls. Plasma levels of progesterone (P) and luteinizing hormone (LH), are not significantly changed in different stages of endometriosis with respect to healthy controls. The significant decrease of follicle-stimulating hormone (FSH) plasma levels found in either stages I/II or III/IV endometriosis patients is not correlated with the NK cell activity. In conclusion, at advanced stages of endometriosis the impairment of NK cell activity occurs with increased E2, and decreased PRL plasma levels. Additional studies are required to determine whether the E2/PRL ratio represents a possible biochemical marker of endometriosis.\nSimilar content being viewed by others\nReferences\nBarbieri R.L. Etiology and epidemiology of endometriosis. Am. J. Obstet. Gynecol. 162:565, 1990.\nJanne O., Kaupilla A., Kokko E. Estrogen and progestin receptors in endometriosis lesions: comparison with endometrial tissue. Am. J. Obstet. Gynecol. 141:562, 1981.\nSteele R.W., Dmowsky W.P., Marmer D.J. Immunologic aspects of human endometriosis. Am. J. Reprod. Immunol. 6:33, 1984.\nOosterlynch D.J., Cornillie F.J., Waer M., Vandeputte M., Koninckx P.R. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fert. Steril. 56:45, 1991.\nLotzovà E. Definition and functions of natural killer cells. Nat. Immun. Cell Growth Regul. 12:169, 1993.\nLotzovà E., Herberman R.B. Immunobiology of natural killer cells. CRC Press, Boca Raton, 1986; Vol. I and II.\nPollack S.B. Production and differentiation of NK lineage cells in bone marrow. Nat. Immun. 12.177,1993.\nGarzetti G.G., Ciavattini A., Provinciali M., Fabris N., Cignitti M., Romanini C. Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity. Obstet. Gynecol. 81:665, 1993.\nFabris N., Provinciali M. Natural Immunity. In: Nelson D.S. (Ed.), Hormones. Academic Press, Sydney, 1989, p. 306.\nAcien P., Lloret M., Graells M. Prolactin and its response to the luteinizing hormone releasing hormone, thyrotropin release hormone test in patients with endometriosis before, during and after treatment with danazole. Fert. Steril. 51:774, 1989.\nRadwanska E., Henig I., Dmowski W.P. Nocturnal prolactin levels in infertile women with endometriosis. J. Reprod. Med. 32:605, 1987.\nWallace A.M., Lees D.A.R., Roberts A.D.G. Danazol and prolactin status in patients with endometriosis. Acta Endocrinol. (Copenh.) 107:445, 1984.\nCross R.J., Roszman T.L. Neuroendocrine modulation of immune function: the role of prolactin. Prog in Neuroendocrinimmunol. 2:17, 1989.\nBernton E.W. Prolactin and immune host defenses. Prog. Neuroendocrinimmunol. 2:21, 1989.\nMatera L., Bellone G., Cesano A. Prolactin and the neuroimmune network. Adv. Neuroimmunol. 1:158, 1991.\nMatera L., Muccioli G., Cesano A., Bellussi G., Genazzani E. Prolactin receptors on large granular lymphocytes: dual regulation by cyclosporin A. Brain Behav. Immun. 2:1, 1988.\nMatera L., Cesano A., Muccioli G., Veglia F. Modulatory effect of prolactin on the DNA synthesis rate and NK activity of large granular lymphocytes. Int. J. Neurosci. 51:265, 1990.\nMatera L., Cesano A., Bellone G., Oberholtzer E. Modulatory effect of prolactin on the resting and mitogen-induced activity of T, B, and NK lymphocytes. Brain Behav. Immun. 5:409, 1992.\nThe American Fertility Society. Revised American Fertility Society Classification of endometriosis: 1985. Fertil. Steril. 43:351, 1985.\nProvinciali M., Di Stefano G., Fabris N. Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluorescein diac-etate (cFDA) and comparison with conventional 51 Cr release assay. J. Immunol. Methods 155:19, 1992.\nHiestand P.C., Meckler P., Nordmann R., Grieder A. Permmongkol C. Prolactin as a modulator of lymphocyte responsive-ness provides a possible mechanism of action for cyclosporin. Proc. Natl. Acad. Sci. USA 83:2599, 1986.\nGerli R., Rambotti P., Nicoletti I., Orlandi S., Migliorati G., Riccardi C. Reduced number of natural killer cells in patients with pathological hyperprolaetinemia. Clin. Exp. Immunol. 64:399, 1986.\nMatera L., Ciccarelli E., Cesano A., Veglia F., Miola C., Camanni F. Natural killer activity in hyperprolactinemic patients. Immunopharmacol. 18:143, 1989.\nMaurer RA. Relationship between estradiol, ergocriptine and thyroid hormone: effects on prolactin synthesis and prolactin messenger ribonucleic acid levels. Endocrinology 110:1515, 1982.\nEvans W.S., Carlsen E., Key Y. Prolactin and its disorders. In: Kenneth L. Becker (Ed.), Principles and practice of endocrinology and metabolism. JB Lippincott Company, Philadelphia, 1990, p. 134.\nAuthor information\nAuthors and Affiliations\nRights and permissions\nAbout this article\nCite this article\nProvinciali, M., Di Stefano, G., Muzzioli, M. et al. Relationship between 17-ß-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis. J Endocrinol Invest 18, 645–652 (1995). https://doi.org/10.1007/BF03349783\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/BF03349783","source_license":"CC0","license_restricted":false}