Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042755 (masculinization)
2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found.
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PMID:The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. 17 81

We have previously described a group of young females with virilization, acanthosis nigricans, insulin resistance, and markedly decreased binding of insulin to its receptor (syndrome of insulin resistance and acanthosis nigricans type A). The present report concerns a 15-yr-old female with clinical features indistinguishable from the type A patients, including virilization, acanthosis nigricans, and extreme resistance to endogenous and exogenous insulin. Insulin levels were 400-650 microU/ml while fasting and were over 2200 microU/ml when stimulated. Proinsulin was less than 10% of the total immunoassayable insulin. In distinct contrast to the type A patients, insulin receptors on cells from this patient were entirely normal on the basis of specificity, negative cooperativity, affinity, concentration, and interaction with antiinsulin receptor antibodies. These findings suggest the presence of an intracellular defect as the cause of the observed insulin resistance.
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PMID:Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect. 40 Jul 28

We describe the case of a 74-year-old woman with a fifteen-year old history of virilism and with a Type-II-diabetes mellitus treated with insulin. After the removal of the ovaries, the formerly elevated serum-testosterone levels normalised and the signs of virilism gradually abated. The histological finding of stromal thecosis in the ovaries is discussed in relation to hyperinsulinaemia and other potential stimuli for ovarian stromal hyperplasia.
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PMID:[Postmenopausal virilization in thecosis of the ovaries]. 131 96

In a single practice during the 21 years 1971-1991, the incidence of gestational diabetes in pregnancies in which norethisterone was prescribed was 32.4% (22 of 69) in comparison with 7.1% in pregnancies in which the women did not take norethisterone (137 of 1,684) (p < 0.001). Gestational diabetes was no less severe (degree of hyperglycaemia, need for insulin therapy) when associated with norethisterone. However, follow-up revealed that gestational diabetes when associated with norethisterone had a lesser risk of emerging diabetes mellitus and impaired glucose tolerance. Masculinization of a female fetus occurred in 5 of 39 (12.8%) exposed to norethisterone; all were cases of clitoral hypertrophy not requiring surgical treatment. Norethisterone in these 69 pregnancies accounted for 33.3% (5 of 15) cases of clitoral hypertrophy diagnosed in 100,756 consecutive births.
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PMID:Norethisterone and gestational diabetes. 144 34

Previous reports have suggested a relationship between hyperinsulinemia and increased androgen secretion leading to female virilization, but no report has been made of the effects of insulin on androgen receptors. The authors tested the in vitro effect of insulin on the binding of methyltrienolone (R1881) to androgen receptors of cultured genital skin fibroblasts preincubated with serum-free medium in the absence and presence of insulin (100 ng/mL, ie, 2600 microU/mL) for 18 hours at 37 degrees C. Insulin increased specific binding of R1881 by 35% (range, 13% to 75%). Scatchard analysis of androgen receptor binding demonstrated a similar increase in the number of binding sites, whereas binding affinity remained unchanged. The increase in androgen receptors was dose dependent (maximum effect at 25 ng insulin/mL) and time dependent (maximum effect occurring after 12 hours). DNA measurements indicated that insulin increased binding sites per cell rather than altering the cell number. Insulin increased total protein concentration to an extent similar to that observed for the increase in androgen receptor binding sites. Cycloheximide, but no actinomycin D, inhibited the effect of insulin on androgen receptor binding. The authors' data suggest that insulin induces an increase in the number of androgen receptors per cell as part of a general anabolic effect on cellular protein content.
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PMID:Binding of methyltrienolone to androgen receptors in human skin fibroblasts is enhanced by insulin. 160 43

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.
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PMID:Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance. 195 1

Hirsutism as a sign of hyperandrogenism is a common endocrinological disorder in women. Its spectrum varies from mild forms with dominating psychic component to severe forms associated with virilization. The severity should be assessed by semiobjective scoring systems, the use of which also allows the systematic follow-up of the results of treatment. An increase in serum androgen levels or an increased turnover of androgens can be detected in most patients. Enhanced peripheral conversion of androgens to locally acting androgen also leads to hirsutism. The thorough investigation of the endocrinological milieu is required to rule out androgen producing neoplasms. In most patient, however, disturbances are functional, among which polycystic ovary syndrome is the commonest. It is a disorder exhibiting a complexity of changes in endocrinological interactions. Besides inappropriate gonadotropin secretion insulin and insulin like growth factor are also involved. The opioidergic system also seems to be affected. Polycystic ovary syndrome is also associated with obesity and infertility, both of which require attention.
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PMID:Hirsutism: definitions and etiology. 219 64

Thirteen patients with the syndrome of acanthosis nigricans and insulin resistance are described. They all had a combination of dermatoses related to hyperandrogenism (cutaneous virilism): hirsuties (II), acne vulgaris (6), hidradenitis suppurativa (5) and androgenic alopecia (4). In addition, 9 out of 13 had keratosis pilaris. The patients had raised fasting plasma insulin levels compared with matched normal controls (P less than 0.01) and increased insulin resistance (P less than 0.02). Insulin resistance correlated with total serum testosterone (rs = 0.65; P less than 0.02).
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PMID:Acanthosis nigricans, insulin resistance and cutaneous virilism. 329 47

The authors administered to six transsexual women at three-month intervals androgenic depot preparations: testosterone undecanoate (Andriol-Organon) by the oral route and testosterone isobutyrate (Agovirin depot-Spofa) in injections. The achieved changes were evaluated by clinical and laboratory examinations, i.e. somatic changes as well as changes of hormonal indicators in plasma, urine and saliva, changes in the TeBG binding capacity, the effect of the administered hormones on liver functions, glucose metabolism and secretory insulin response. The high plasma androgen level did not vary substantially. After Andriol administration, a significant decrease of plasma TeBG was achieved, and an increase of the free testosterone fraction in saliva which was retained three months after discontinuation of the treatment. Both preparations caused the required virilization, whereby the action of Agovirin depot-Spofa in the selected dose was, as regards the speed of onset and intensity of the androgenization symptoms, more effective. The gonadotropin levels were not changed significantly during short-term administration. No interference with liver functions and glucose metabolism was observed. The patients tolerated both preparations well.
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PMID:Androgen administration to transsexual women. II. Hormonal changes. 355 12

Nine women with acanthosis nigricans and masculinization, who did not appear to have any of the reported syndromes associated with acanthosis nigricans, were studied to characterize the clinical, biochemical, and ovarian morphologic features of their disorders. These patients had the clinical and biochemical profiles of polycystic ovarian disease. All acanthosis nigricans subjects had significant insulin resistance when insulin binding to both circulating monocytes and erythrocytes was compared to the control subjects. Microscopic examination of the ovaries revealed no evidence of recent normal ovulation, sclerosis of the ovarian cortex, follicle cysts, and stromal hyperthecosis. The authors conclude that ovarian stromal hyperthecosis and insulin resistance are consistent findings in the present type of patient. This study provides further evidence supporting a relationship between insulin resistance and human ovarian function.
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PMID:Clinical, biochemical, and ovarian morphologic features in women with acanthosis nigricans and masculinization. 390 Aug 41


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