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Disease relevance of Feminization


Psychiatry related information on Feminization


High impact information on Feminization

  • Loss-of-function mutations in the X-linked gene xol-1 cause the feminization and death of XO animals (normally males) by shifting the sex determination and dosage compensation pathways toward their hermaphrodite modes [8].
  • Gibberellins, steroid-like plant hormones, appear to play a pivotal role in the stamen abortion process and the feminization of floral tissues [9].
  • DDT-induced feminization of gull embryos [10].
  • In summary, ERbeta is essential for the pubertal feminization of the cortical bone in female mice but is not required for the protective effect of estrogens on trabecular BMD [11].
  • Since sufficient estrogen is produced in normal men to induce breast enlargement in the absence of adequate amounts of circulating androgens, it has been generally assumed that androgens exert an antiestrogenic action to prevent feminization in normal men [12].

Chemical compound and disease context of Feminization


Biological context of Feminization


Anatomical context of Feminization


Gene context of Feminization

  • Feminization of the germline depends upon the constitutively expressed transformer-2 (tra-2) gene, but does not seem to require a functional dsx gene [24].
  • Severe alleles of fem-2 also cause complete feminization of XX animals at all temperatures, but feminization of fem-2 XO animals is temperature-sensitive: complete at 25 degrees, incomplete at 20 degrees [27].
  • Mutations in fem-3 resemble alleles of fem-1 (previously characterized): putative null alleles result in complete feminization of XX and XO animals, transforming them into fertile females [27].
  • We recently identified an XY intersex patient carrying a chromosomal duplication of the WNT4 locus and proposed that this patient's feminization arises from an increased dosage of WNT4 [28].
  • Thus, ERalpha appears to play a key role in the mechanism that inhibits nuclear localization of Stat5b in female mice, leading to feminization of a ERalpha-GH-Stat5b pathway and Cyp expression [29].

Analytical, diagnostic and therapeutic context of Feminization

  • Passive immunization during 4 days by multiple injections of an antiserum generated against somatostatin resulted in a partial feminization of the male rat liver [30].
  • Castration of adult (9-month-old) male rats caused a decrease in drug metabolism, but did not result in complete feminization of the profiles of drug metabolism as was observed in old male rats, indicating that neonatally imprinted male pattern of drug metabolism was still retained in the absence of testosterone in adult male rats [31].
  • Furthermore, the fact that ovariectomy was effective as late as day 16, while TP treatment on day 8 or later had no effect, suggests that masculinization and feminization of this structure constitute separate processes with distinct sensitive periods [32].
  • Reproductive and ultrasonographic evaluation, testosterone assays, and karyotyping confirmed a diagnosis of androgen insensitivity syndrome (64, XY--testicular feminization) [33].
  • BACKGROUND: Most girls with Turner syndrome (TS) need estrogen replacement treatment (ERT) to induce and maintain feminization and prevent osteoporosis [34].


  1. The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats. Stauber, R.E., Rosenblum, E., Eagon, P.K., Gavaler, J.S., Van Thiel, D.H. Gastroenterology (1991) [Pubmed]
  2. Hypogonadism precedes liver feminization in chronic alcohol-fed male rats. Tadic, S.D., Elm, M.S., Subbotin, V.M., Eagon, P.K. Hepatology (2000) [Pubmed]
  3. Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: role of IL-6. Morales-Montor, J., Baig, S., Mitchell, R., Deway, K., Hallal-Calleros, C., Damian, R.T. J. Immunol. (2001) [Pubmed]
  4. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. Skogseid, B., Larsson, C., Lindgren, P.G., Kvanta, E., Rastad, J., Theodorsson, E., Wide, L., Wilander, E., Oberg, K. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  5. Interstitial cell tumor. Profile of hormone-producing tumor. Herwig, K.R., Vinson, R.K. Urology (1978) [Pubmed]
  6. Estradiol and para-chlorophenylalanine downregulate the expression of brain aromatase and estrogen receptor-alpha mRNA during the critical period of feminization in tilapia (Oreochromis mossambicus). Tsai, C.L., Wang, L.H., Fang, L.S. Neuroendocrinology (2001) [Pubmed]
  7. Can alcohol promote aromatization of androgens to estrogens? A review. Purohit, V. Alcohol (2000) [Pubmed]
  8. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Miller, L.M., Plenefisch, J.D., Casson, L.P., Meyer, B.J. Cell (1988) [Pubmed]
  9. The sex determination process in maize. Dellaporta, S.L., Calderon-Urrea, A. Science (1994) [Pubmed]
  10. DDT-induced feminization of gull embryos. Fry, D.M., Toone, C.K. Science (1981) [Pubmed]
  11. Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERbeta(-/-) mice. Windahl, S.H., Vidal, O., Andersson, G., Gustafsson, J.A., Ohlsson, C. J. Clin. Invest. (1999) [Pubmed]
  12. Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. Casey, R.W., Wilson, J.D. J. Clin. Invest. (1984) [Pubmed]
  13. Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy. Hemsell, D.L., Edman, C.D., Marks, J.F., Siiteri, P.K., MacDonald, P.C. J. Clin. Invest. (1977) [Pubmed]
  14. Feminization of the alcoholic: the estrogen/testosterone ratio (E/T). Lester, R., Eagon, P.K., Van Thiel, D.H. Gastroenterology (1979) [Pubmed]
  15. Effect of spironolactone and potassium canrenoate on cytosolic and nuclear androgen and estrogen receptors of rat liver. Francavilla, A., Di Leo, A., Eagon, P.K., Polimeno, L., Guglielmi, F., Fanizza, G., Barone, M., Starzl, T.E. Gastroenterology (1987) [Pubmed]
  16. Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila. Belgacem, Y.H., Martin, J.R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans. Wang, S., Kimble, J. EMBO J. (2001) [Pubmed]
  18. Effect of cis-platinum on heme, drug, and steroid metabolism pathways: possible involvement in nephrotoxicity and infertility. Maines, M.D. Crit. Rev. Toxicol. (1990) [Pubmed]
  19. Hydroxylated polychlorinated biphenyl metabolites are anti-estrogenic in a stably transfected human breast adenocarcinoma (MCF7) cell line. Kramer, V.J., Helferich, W.G., Bergman, A., Klasson-Wehler, E., Giesy, J.P. Toxicol. Appl. Pharmacol. (1997) [Pubmed]
  20. Partial demasculinization and feminization of sex behavior in male rats by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin is not associated with alterations in estrogen receptor binding or volumes of sexually differentiated brain nuclei. Bjerke, D.L., Brown, T.J., MacLusky, N.J., Hochberg, R.B., Peterson, R.E. Toxicol. Appl. Pharmacol. (1994) [Pubmed]
  21. Peptide hormones versus steroid hormones: case studies from snail and turtle populations. Oberdorster, E. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  22. Specification of male development in Caenorhabditis elegans: the fem genes. Kimble, J., Edgar, L., Hirsh, D. Dev. Biol. (1984) [Pubmed]
  23. Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Imperato-McGinley, J., Sanchez, R.S., Spencer, J.R., Yee, B., Vaughan, E.D. Endocrinology (1992) [Pubmed]
  24. Sex determination in the Drosophila germline is dictated by the sexual identity of the surrounding soma. Waterbury, J.A., Horabin, J.I., Bopp, D., Schedl, P. Genetics (2000) [Pubmed]
  25. Inhibition of testicular development and feminization of the male genitalia by neonatal estrogen treatment in a marsupial. Fadem, B.H., Tesoriero, J.V. Biol. Reprod. (1986) [Pubmed]
  26. Pretranslational down-regulation of male specific hepatic P450s after portal bypass. Jiang, X.M., Cantrill, E., Farrell, G.C., Murray, M. Biochem. Pharmacol. (1994) [Pubmed]
  27. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Hodgkin, J. Genetics (1986) [Pubmed]
  28. Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy. Jordan, B.K., Shen, J.H., Olaso, R., Ingraham, H.A., Vilain, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Developmental action of estrogen receptor-alpha feminizes the growth hormone-Stat5b pathway and expression of Cyp2a4 and Cyp2d9 genes in mouse liver. Sueyoshi, T., Yokomori, N., Korach, K.S., Negishi, M. Mol. Pharmacol. (1999) [Pubmed]
  30. Possible role of somatostatin in the regulation of the sexually differentiated steroid metabolism and prolactin receptor in rat liver. Norstedt, G., Mode, A., Hökfelt, T., Eneroth, P., Elde, R., Ferland, L., Labrie, F., Gustafsson, J.A. Endocrinology (1983) [Pubmed]
  31. Alteration of plasma sex hormone levels associated with old age and its effect on hepatic drug metabolism in rats. Fujita, S., Chiba, M., Ohta, M., Kitani, K., Suzuki, T. J. Pharmacol. Exp. Ther. (1990) [Pubmed]
  32. Corpus callosum: ovarian hormones and feminization. Fitch, R.H., Cowell, P.E., Schrott, L.M., Denenberg, V.H. Brain Res. (1991) [Pubmed]
  33. Androgen insensitivity syndrome in a thoroughbred mare (64, XY--testicular feminization). Howden, K.J. Can. Vet. J. (2004) [Pubmed]
  34. The importance of estrogen replacement in young women with Turner syndrome. Hanton, L., Axelrod, L., Bakalov, V., Bondy, C.A. Journal of women's health (2002) (2003) [Pubmed]
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