Disease relevance of Feminization

• Signs of feminization are seen in men with cirrhosis of alcoholic but also of nonalcoholic origin even in the absence of markedly increased plasma estrogen levels [1].
• Men who chronically abuse alcohol may display a spectrum of endocrine abnormalities including hypogonadism and feminization, with elevated serum estradiol and low serum testosterone [2].
• Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: role of IL-6 [3].
• The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements [4].
• The feminization and psychologic changes most likely reflect production of estrogen by the interstitial cell tumor [5].

Psychiatry related information on Feminization

• 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) [6].
• Increased aromatization may be a mechanism for feminization of some male alcoholics, as well as for the reported increases in plasma estrogen levels in postmenopausal women subjected to moderate alcohol consumption [7].

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

• Feminization in men occurs when the effective ratio of androgen to estrogen is lowered [12].
• Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy [13].
• Feminization of the alcoholic: the estrogen/testosterone ratio (E/T) [14].
• The administration of spironolactone frequently leads to feminization, which has been noted less frequently with the use of potassium canrenoate, a salt of the active metabolite of spironolactone [15].
• Finally, feeding males with fluvastatin, a juvenile hormone (JH) inhibitor, also led to start/stop feminization, and this effect is reversible by the simultaneous application of methoprene, a JH analog, suggesting the existence of a neuroendocrine control, by JH, of such behavioral dimorphism [16].

Biological context of Feminization

• The functional importance of the TRA-1-TRA-2 physical interaction is supported by genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra-1 gene dose from two copies to one copy enhances the tra-2(mx) feminization phenotype, but has no apparent somatic effect [17].
• In the liver, a feminization of the cytochromes P-450 profile is produced, and hence the biotransformation of endogenous steroids as well as that of exogenous chemicals is affected [18].
• OHCBs have been associated with inhibition of vitamin A and thyroxin transport, estrogenicity in a mouse uterotrophic assay, and feminization of male turtle sexual development [19].
• 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 [20].
• Steroid hormones play a role in feminization of oviparous vertebrates [21].

Anatomical context of Feminization

• Mutation of the gene fem-2 causes feminization of both sexes: hermaphrodites make no sperm, and males produce oocytes in an intersexual somatic gonad [22].
• In flutamide-treated animals, complete feminization of the genitalia occurred at 24 mg/kg.day in all animals [23].
• However, feminization of XY germ cells by Tra(F) can be blocked by the male form of the Dsx protein (Dsx(M)) [24].
• Inhibition of testicular development and feminization of the male genitalia by neonatal estrogen treatment in a marsupial [25].
• Thus, the endocrine effects of portal bypass result in biochemical demasculinization, but not feminization, of hepatic enzymes involved in steroid biotransformation [26].

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].

References