Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In C3H mice, a major component of susceptibility to the diabetogenic action of an obesity mutation (diabetes, db) is male gender associated. We tested whether increased male susceptibility was an androgen receptor mediated process. C3H.SW/Lt-derived db/db males were rendered androgen-receptor function-deficient by introducing the testicular feminization (Tfm) mutation of the X-linked androgen receptor gene. The db/db Tfm/Y males (phenotypically female in appearance) developed severe diabetes indistinguishable from that observed in standard db/db X + Y males. Castration of standard C3H.SW/Lt-db/db males (producing mutants with normal androgen receptors but reduced serum testosterone) also failed to block the gender-enhanced susceptibility. In contrast, female db/db littermates exhibited a milder hyperglycemia, and were more resistant to pancreatic beta cell necrosis and islet atrophy than any of the groups of db/db males. Although these data indicated that male-enhanced sensitivity to diabetogenic stress was independent of circulating androgens, the possibility that the gender dimorphism is predicated upon tissue ratios of active estrogens to androgens in glucose-producing tissues such as liver is discussed.
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PMID:Effect of androgen insensitivity on diabetogenesis in db/db male mice with testicular feminization (Tfm). 187 72

Controversy concerning the most appropriate treatment guidelines for intersex children currently exists. This is due to a lack of long-term information regarding medical, surgical, and psychosexual outcome in affected adults. We have assessed by questionnaire and medical examination the physical and psychosexual status of 14 women with documented complete androgen insensitivity syndrome (CAIS). We have also determined participant knowledge of CAIS as well as opinion of medical and surgical treatment. As a whole, secondary sexual development of these women was satisfactory, as judged by both participants and physicians. In general, most women were satisfied with their psychosexual development and sexual function. Factors reported to contribute to dissatisfaction were sexual abuse in one case and marked obesity in another. All of the women who participated were satisfied with having been raised as females, and none desired a gender reassignment. Although not perfect, the medical, surgical, and psychosexual outcomes for women with CAIS were satisfactory; however, specific ways for improving long-term treatment of this population were identified.
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PMID:Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. 1094 63

An androgen receptor (AR) null mutant mice line was generated by means of a Cre-lox P system. The male (AR(L-/Y)) (KO) mice exhibited typical features of testicular feminization mutant (Tfm) disease in external reproductive organs with growth retardation. The growth curve of the male AR KO mice was similar to that of the wild-type female littermates until the 10th week of age, but thereafter a drastic increase in the growth was observed with development of obesity. Clear increase in the wet weights of white adipose tissues, but not of brown adipose tissue, was found in the 30-week-old male AR KO mice. However, no significant alteration in serum lipid parameters and food intake was observed. Thus, the present results suggest that AR may serve as a negative regulator of adipose development in adult males.
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PMID:Late onset of obesity in male androgen receptor-deficient (AR KO) mice. 1248 May 37

The androgen receptor (AR) is a ligand-dependent transcription factor involved in the regulation of many different physiological processes. AR dysfunction causes a diverse range of clinical conditions, including testicular feminization mutation (Tfm) syndrome, prostate cancer, and motor neuron disease (Kennedy's disease). However, due to lack of genetic models, the molecular basis of the AR in these disorders remains largely unknown. Using a conditional targeting technique based on the Cre-loxP system, we successfully generated null AR mutant (ARKO) mice. ARKO males exhibited normal healthy growth, but showed typical Tfm abnormalities. Hormonal assay of ARKO males revealed that while serum androgen levels were very low, estrogen levels were normal. Another hallmark of ARKO males was late-onset obesity, with marked accumulation of white adipose tissue. To clarify the role of human AR (hAR) mutants with expanded polyQ stretches as observed in neurodegenerative disease, we also established a Drosophila model in which either wild-type or polyQ-expanded hAR were ectopically expressed. Although no overt phenotype was detected in adult fly-eye neurons expressing mutant hAR, the ingestion of androgen caused marked neurodegeneration.
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PMID:Androgen receptor functions from reverse genetic models. 1294 92

Clinical and experimental data suggest that androgen receptor (AR) signaling plays a role on body composition, glucose homeostasis and lipid metabolism. The effect of AR disruption on such parameters was not extensively investigated in human people. A group of young to middle-age adult women with complete androgen insensitivity syndrome (CAIS, n = 18, age 32.2 +/- 9.3 years; women with testes removed n = 14) was investigated for body mass index (BMI), body composition (dual energy X-ray absorptiometry), serum glucose levels, insulin sensitivity (HOMA-IR) and lipid profile. Mean BMI (24.2 +/- 7.4 kg/m(2)) was not significantly increased (T-score 1.0 +/- 2.5, p = NS vs Italian female reference values), but prevalence of obesity was higher in women with CAIS than that reported in age-related Italian females (16.7% vs 3.6%, respectively). The majority of obese individuals with CAIS was in the subgroup with intact testes (3/4). DXA assessment (n = 15) demonstrated values of total free fat mass similar to that of 46,XX female controls. Increased body fat was found in CAIS women in comparison with both female and male controls. Abnormal values of cholesterol (total and LDL) and HOMA-IR were present in a large subset of patients. Our data suggest that in women with CAIS disruption of AR signaling may increase body fat and affect some metabolic parameters. Assessment of body composition, metabolic profile and, likely, cardiovascular risk seems to be advisable with ageing in these individuals.
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PMID:Body composition and metabolic profile in women with complete androgen insensitivity syndrome. 1975 98

The androgen receptor (AR) is a ligand-dependent transcription factor involved in the regulation of many different physiological processes. Dysfunction of AR causes diverse clinical conditions, such as testicular feminization mutation (Tfm) syndrome and prostate cancer. However, the molecular basis of the AR in these disorders largely remains unknown, as a result of a lack of genetic models. Using conditional targeting technique with Cre-loxP system, we successfully generated null AR mutant (ARKO) mice. The ARKO males grew healthily, but they showed typical Tfm abnormalities. The ARKO males exhibited late onset of obesity with impaired bone metabolism and sexual behaviors. No overt abnormality was found in female ARKO mice, but a premature ovarian failure-like phenotype was found with impaired folliculogenesis. Thus, andorogen/AR system supports normal reproduction as well as normal female reproduction. (Reprod Med Biol 2007; 6: 11-17).
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PMID:Androgen receptor functions in male and female reproduction. 2969 61