Disease relevance of Genitalia

• Male and female Ftz-F1 null mice had female internal genitalia, despite complete gonadal agenesis [1].
• Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH [2].
• Consequently, impairment of AR function can result in undermasculinized genitalia that vary from a completely female appearance to isolated hypospadias [3].
• Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate [4].
• Multiple lentigines/LEOPARD syndrome (LS) is a rare, autosomal dominant disorder characterized by Lentigines, Electrocardiogram abnormalities, Ocular hypertelorism, Pulmonic valvular stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness [5].

Psychiatry related information on Genitalia

• The proband, an 18 year old boy, showed mental retardation, severe dysmorphic features, hypogonadotrophic hypogonadism (HHG), and hypoplastic external genitalia [6].
• Males carrying a hypomorphic mutation in lig fail to withdraw their genitalia upon termination of copulation, but display no overt abnormalities in their genitalia [7].
• Critical period of induction by tamoxifen of genital organ abnormalities in female mice [8].

High impact information on Genitalia

• Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia [9].
• Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin [9].
• Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group [10].
• Long duration androgen treatments masculinized both behavior and genitalia suggesting that socializing responses to the females' male-like appearance may have produced the behavioral changes [11].
• In a third family, the external genitalia were predominantly male at birth, and sex-of-rearing has been male: their codon 839 has mutated to cysteine [12].

Chemical compound and disease context of Genitalia

• We have studied a kindred in which two parts of siblings, maternal first cousins, have a form of "minimal" androgen insensitivity that permits morphogenesis of unambiguous male external genitalia, but interferes with normal virilization at puberty [13].
• Testosterone is essential for the correct development of male internal and external genitalia; hence, deleterious mutations in the HSD17B3 gene give rise to a rare form of male pseudohermaphroditism termed 17betaHSD deficiency [14].
• In the disorder familial incomplete male pseudohermphroditism, type 2, deficient dihydrotestosterone formation is associated with a selective failure of virilization of the urogenital sinus and external genitalia, whereas the wolffian duct derivatives develop normally [15].
• These results confirm the genotoxicity of zearalenone and its ability to induce hepatocellular adenomas, rather than tumours of genital organs, in mice [16].
• Guinea pigs were infected intravaginally with HSV-2 and treated both intravaginally and topically on the external genitalia four times a day with 1% or 5% 2-DG in miconazole nitrate cream [17].

Biological context of Genitalia

• Our large survey of patients with ABS shows that individuals with an ABS-like phenotype and normal steroidogenesis have FGFR mutations, whereas those with ambiguous genitalia and disordered steroidogenesis should be recognized as having a distinct new disease: POR deficiency [18].
• The SRY gene of five subjects with 46,XY complete gonadal dysgenesis (46,XY karyotype, completely female external genitalia, normal Müllerian ducts, and streak gonads) was evaluated for possible mutations in the coding region by using both single-strand conformation polymorphism (SSCP) assay and DNA sequencing [19].
• The phenotypic expression of TDF in the presence of two X chromosomes is a male habitus, dysgenetic scrotal testes and no ambiguity of the genitalia [20].
• Requirement of Abdominal-A and Abdominal-B in the developing genitalia of Drosophila breaks the posterior downregulation rule [21].
• The male gonad, in turn, normally produces hormones such as testosterone and Mullerian inhibiting substance (MIS) that regulate differentiation of the internal and external genitalia, thus determining phenotypic sex [22].

Anatomical context of Genitalia

• Nuclear transfer of androgen receptors (AR) and glucocorticoid receptors (GR) was determined in cultured genital skin fibroblasts from 10 normal controls and eight patients with abnormalities of the external genitalia [23].
• Loss of both spalt and spalt-related function in flies yields morphological defects in the testes, genitalia, and the antenna [24].
• X-linked lissencephaly with absent corpus callosum and ambiguous genitalia is a newly recognized syndrome responsible for a severe neurological disorder of neonatal onset in boys [25].
• We have studied the function of Abdominal-B in the formation of Drosophila genitalia, and show here that absence of Abdominal-B in the genital disc of Drosophila transforms male and female genitalia into leg or, less frequently, into antenna [26].
• The MK gene was, therefore, widely expressed in neoplastic cells originating from genital organs, intestinal tract, liver, mammary gland, and urinary tract, and the expression was not restricted to adenocarcinomas, but was also observed in other types of tumor cells [27].

Associations of Genitalia with chemical compounds

• Diagnosis of the enzymatic defect is based on the clinical picture of ambiguous genitalia and salt-losing crisis in infancy, together with high urinary delta5-pregnenetriol and plasma dehydroepiandrosterone when the patient was taken off replacement corticoid treatment [28].
• We report a 46,XY infant with an M807T mutation in his androgen receptor that abrogated cellular responses to testosterone, but not to dihydrotestosterone (DHT), resulting in ambiguous genitalia [29].
• Ambiguous genitalia in infant exposed to tamoxifen in utero [30].
• The arachidonic acid cascade is involved in the masculinizing action of testosterone on embryonic external genitalia in mice [31].
• Longer polyglutamine tracts in the androgen receptor are associated with moderate to severe undermasculinized genitalia in XY males [3].

Gene context of Genitalia

• In the male A9, some Abd-B m(-)r(-) or Abd-B r(-) clones activate Distal-less and transform part of the genitalia into leg or antenna [21].
• Unique functions of Sonic hedgehog signaling during external genitalia development [32].
• Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation [33].
• However, the abnormal external genitalia development of Fgf10(-/-) perinatal mice suggested the importance of Fgf10 in the development of the glans penis and the glans clitoridis [33].
• We show that the gene dachshund (dac) is differentially expressed in the male and female genital discs, and plays sex-specific roles in the development of the genitalia [34].

Analytical, diagnostic and therapeutic context of Genitalia

• Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs [35].
• The progestin treatment resulted in a lowering of plasma levels of testosterone, androstenedione, and LH, as well as in a reduction of epididymal sperm counts and accessory sex organ weights [36].
• The accumulation of dihydrotestosterone in accessory sex organ nuclei was saturable, inhibited by perfusion of excess testosterone or cyproterone acetate, and associated with binding to 3S salt-extractable molecules [37].
• Orchiectomy and pretreatment with ethinyl estradiol resulted in a moderate to slight decrease in binding in the accessory sex organs [38].
• Proliferative response of rat accessory sex organs to dietary sex hormones after castration or initial dietary administration of estrogen [39].

References