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In vivo antiestrogenic activity of mifepristone in the rat

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Abstract

The aim of this study was to find out whether mifepristone, known mainly as a substance with an antiprogesterone and antiglucocorticoid effect, also has an in vivo antiestrogenic activity on the adenohypophysis of the rat. Male Wistar rats were given chronically either estradiol-benzoate (EB, 1 mg s.c. twice a week) for a period of 12 days, or the non steroidal antiestrogen tamoxifen (1 mg/day/rat), or mifepristone (1 mg/day/rat), or EB together with mifepristone or tamoxifen. The hypertrophic effect of the EB on the weight of the adenohypophysis (AP) was significantly suppressed both by tamoxifen and by mifepristone. Mifepristone and tamoxifen reduced the increased content of PRL in the estrogenized adenohypophysis. Mifepristone but not tamoxifen significantly increased the content of the LH in the adenohypophysis of estrogen treated rats. Mifepristone and tamoxifen suppressed the increased concentration of cyclic nucleotides cAMP and cGMP in the estrogenized adenohypophysis. Mifepristone given alone increased serum levels of corticosterone, but when given together with EB deepened inhibiting effect EB on them. The results of our preliminary study show that mifepristone exerts a weak antiestrogenic activity on the level of hypophysis, however the pharmacology is not identical to tamoxifen.

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References

  1. Kawai S., Nieman L.K., Brandon D.D., Udelsman R., Loriaux D.L., Chrousos G.P. Pharmacokinetic properties of the antiglucocortiocoid and antiprogesterone steroid RU 486 in man. J. Pharmacol. Exp. Ther. 241: 401, 1987.

    PubMed  CAS  Google Scholar 

  2. Jellinck P.H., Newcombe A.M., Lyttle C.R. Antiandrogenic property of RU 486: enhancement of estrogen-induced uterine peroxidase activity in the rat. J. Steroid biochem. Mol. Biol. 45: 303, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Moguilewsky M., Philibert D. Biochemical profile of RU 486. In: E.E. Baulieu, S.J. Segal (Ed.), The Antiprogestin Steroid RU 486 and Human Fertility Control. Plenum Publ. Corp., p. 87.

  4. Wolf J.P., Hsiu J.G., Anderson T.L., Ulman A., Baulieu E.E., Hodgen G.D. Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen-stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrate monkeys. Fert. Steril. 52: 1055, 1989.

    CAS  Google Scholar 

  5. Slayden O.D., Brenner R.M. RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatta). J. Clin. Endocrinol. Metab. 78: 440, 1994.

    PubMed  CAS  Google Scholar 

  6. McDonell D.P., Goldman M.E. RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism. J. Biol. Chem. 269: 11945, 1994.

    Google Scholar 

  7. Nedvídková J., Pacák K., Nedvídek J., Goldstein D.S., Schreiber V. Triiodothyronine attenuates estradiol-induced increases in dopamine D-2 receptor number in rat antwrior pituitary. Brain Res. 712: 148, 1996.

    Article  PubMed  Google Scholar 

  8. Bauer-Dantoin A.C., Tabesh B., Norgle J.R., Levine J.E. RU486 administration blocks neuropeptide Y potentiation of luteinizing hormone (LH)-releasing hormone-induced LH surges in proestrous rats. Endocrinology 133: 2418, 1993.

    PubMed  CAS  Google Scholar 

  9. Kling M.A., Demitrack M.A., Whitfield H.J., Kalogeras K.T., Listwak S.J., DeBellis M.D., Chrousos G.P., Gold P.W., Brandt H.A. Effects of the glucocorticoid antagonist RU 486 on pituitary-adrenal function in patients with anorexia nervosa and health volunteers: Enhancement of plasma ACTH and Cortisol secretion in underweight patients. Neuroendocrinology 57: 1082, 1993.

    Article  PubMed  CAS  Google Scholar 

  10. Li Z., Huang Ch., Klindt J., Anderson L.L. Stimulation of prolactin’secretion in the pig: Central effects of Relaxin and the antiprogesterone RU 486. Endocrinology 133: 1205, 1993.

    PubMed  CAS  Google Scholar 

  11. Stevenson J.S., Cox N.M., Britt J.H. Role of the ovary in controlling luteinizing hormone, follicle stimulating hormone and prolactin secretion during and after lactation in pigs. Biol. Reprod. 24: 341, 1981.

    Article  PubMed  CAS  Google Scholar 

  12. Schreiber V., Nedvídková J., Jahodová J. Anterior pituitary weight, cAMP, cGMP and prolactin levels after combined treatment with estradiol and methylene blue. Physiol. Res. 42: 171, 1993.

    CAS  Google Scholar 

  13. Fuentes M.A., Muldoon T.G., Mahesh V.B. Inhibitory effect of progesterone on occupied estrogen receptors of the anterior pituitary and uterus in adult rats. J. Neuroendocrinol. 2: 517, 1990.

    Article  PubMed  CAS  Google Scholar 

  14. Rao I.M., Mahesh V.B. Role of progesterone in the modulation of the preovulatory surge of gonadotropins and ovulation in the pregnant marens serum gonadotropin-primed immature rat and the adult rat. Biol. Reprod. 35: 1154, 1986.

    Article  PubMed  CAS  Google Scholar 

  15. Shoupe D., Mishell Jr D.R., Lahteenmaki P., Heikinheimo O., Birgerson L., Madkour H., Spitz I.M. Effects of the antiprogesterone RU 486 in normal women. I. Single-dose administration in the midluteal phase. Amer. J. Obstet. Gynecol. 157: 1415, 1987.

    Article  CAS  Google Scholar 

  16. van der Schoot P., Uilenbroek J.T., Slappendel E.J. Effect of the progesterone antagonist mifepristone on the hypothalamo-hypophyseal-ovarian axis in rats. J. Endocrinol. 124: 425, 1990.

    Article  PubMed  Google Scholar 

  17. Sanchez-Criado J.E., Uilenbroek J.T., Karels B. Different effects of the antiprogesterone RU 486 on progesterone secretion by the corpus luteum of rats with 4- and 5- day oestrous cycles. J. Endocrinol. 132: 115, 1992.

    Article  PubMed  CAS  Google Scholar 

  18. Brann D.W., Rao I.M., Mahesh V.B. Antagonism of estrogen induced PRL release by progesterone. Biol. Reprod. 39: 1067, 1988.

    Article  PubMed  CAS  Google Scholar 

  19. Caron R.W., Salicioni A.M., Deis R.P. Mifepristone treatment demonstrates the participation of adrenal glucocorticoids in the regulation of oestrogen-induced prolactin secretion in ovarectomized rats. J. Steroid. Biochem. Mol. Biol. 48: 385, 1994.

    Article  PubMed  CAS  Google Scholar 

  20. Gautvik K.M., Iversen J.E., Sand O. On the role of extracellular Ca2+ for protein release and adenosine 3, 5-monophosphate formation induced by thyreoliberin in cultured rat pituitary cells. Life Sci. 26: 995, 1980.

    Article  PubMed  CAS  Google Scholar 

  21. Swenen L., Bass M., Denef C. Beta-adrenergic stimulation of adenosine-3, 5-monophosphate (cAMP) accumulation and of prolactin and growth hormone secretion in rat anterior pituitary cell cultures. Neuroendocrinology 40: 72, 1985.

    Article  Google Scholar 

  22. Nedvídková J., Schreiber V. The increase in cAMP and cGMP levels in the oestrogenized rat hypophysis. Physiol. Res. 41: 279, 1992.

    PubMed  Google Scholar 

  23. Labrie F., Pelletier G., Lemay A., Borgeat P., Barden N., Dupont A., Savary M., Cote I., Boucher R. Control of protein synthesis in anterior pituitary gland. Karolinska symposia on research methods in reproductive endocrinology. 6th Symposium: Protein Synthesis in Reproductive Tissues. Karolinska Institute, Stockholm, 1973.

  24. Gordon N.D. Editorial comments: Cyclic nucleotides and cellular events related to cell growth. In: Hamet P., Sands H. (Ed.), Advances in cyclic nucleotide research. Raven Press, New York, 1980, Vol. 12, p. 147.

    Google Scholar 

  25. Ortmann O., Hansemann K., Knuppen R., Emons G. Modulatory actions of the new antiprogestins ZK 98.299 and ZK 98.734 and of RU 486 on luteinizing hormone secretion and progesterone effects in pituitary gonadotrophs. J. Steroid. Biochem. 36: 431, 1990.

    Article  PubMed  CAS  Google Scholar 

  26. Lesoon L.A., Mahesh V.B. Stimulatory and inhibitory effects of progesterone on FSH secretion by the anterior pituitary. J. Steroid. Biochem. Mol. Biol. 42: 479, 1992.

    Article  PubMed  CAS  Google Scholar 

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Nedvídková, J., Schreiber, V. & Stárka, L. In vivo antiestrogenic activity of mifepristone in the rat. J Endocrinol Invest 20, 225–229 (1997). https://doi.org/10.1007/BF03346908

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