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)

Congenital adrenal hyperplasia results from 21-hydroxylase deficiency in more than ninety percent of cases. The classical form of 21-hydroxylase deficiency presents in the neonatal period with virilization or adrenal insufficiency, with or without concurrent salt wasting. We report on a rare case of classic 21-hydroxylase deficiency diagnosed in late adulthood. A 39-year-old male patient presented for workup of infertility. Urologic investigation revealed small testes, bilateral testicular masses, and asthenozoospermia. The patient's steroid metabolism showed markedly increased levels of adrenal androgens, in particular of 17-hydroxyprogesterone amd 21-deoxycortisol. The gas chromatographic-mass spectrometric (GC-MS) urinary steroid profile was dominated by metabolites of 17-hydroxyprogesterone, while the endogenous glucocorticoid production was subnormally low. ACTH levels in plasma were elevated. These hormonal findings were consistent with 21-hydroxylase deficiency. Therapy with dexamethasone was initiated. The CTP21A2 gene analysis revealed the mutation I172N (ATC --> AAC) in exon 4 of allele 1 and a large gene deletion in allele 2. Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, clinicians should be alert of this possibility.
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PMID:Late diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1670 55

Gonadotrophin resistance is caused by inactivating mutations in receptors (Rs) of the two gonadotrophins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), presenting as hypergonadotrophic hypogonadism and infertility/subfertility in both sexes. These conditions are extremely rare, but must be kept in mind upon differential diagnosis of disorders of sexual maturation, hypogonadism and infertility. In 46,XY individuals inactivation of LHR causes a disturbance in male-type sexual differentiation that ranges from male pseudohermaphroditism (complete lack of genital masculinization) to mild conditions such as cryptorchidism and hypospadias, depending on completeness of the receptor inactivation. In women, the phenotype is milder, presenting mainly as anovulatory amenorrhoea and hypo-oestrogenization. Inactivation of FSHR causes in otherwise normally masculinized men small testis size and variably reduced spermatogenesis, but not azoospermia or absolute infertility. In women the phenotype is more severe, with primary or early secondary amenorrhoea, arrested follicular maturation and anovulatory infertility. Incomplete forms with milder phenotype and partial responsiveness to FSH have also been described. Although gonadotrophin resistance is a very rare condition, its correct diagnosis is important for the selection of adequate treatment.
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PMID:Gonadotrophin resistance. 1716 32

During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency, are to prevent salt loss and virilization and to achieve normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. Indeed, long-term evaluation of adult CAH patients enables the identification of multiple clinical, hormonal and metabolic abnormalities as bone mineral density alteration, overweight and disturbed reproductive functions. In women with classic CAH, low fertility rate is reported, and is probably the consequence of multiple factors, including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. These patients should therefore be carefully followed-up, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens, by multidisciplinary teams who have knowledge of CAH.
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PMID:Hormonal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1768 81

During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization and to attain normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. The aims here are to review the multiple clinical, hormonal and metabolic abnormalities that could be found in adult CAH patients as such a decrease in bone mineral density, overweight and disturbed reproductive functions. In women with classic CAH, a low fertility rate is reported, and is probably the consequence of multiple factors including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. Therefore a multidisciplinary team with knowledge of CAH should carefully follow up these patients, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens.
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PMID:Classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults. 1820 67

Roles for oestrogens in brain masculinization/sexual behaviour, regulation of follicle-stimulating hormone (FSH)secretion and Leydig cell development and function are well established. However, the widespread distribution of oestrogen receptors alpha and beta in reproductive and other tissues of the male, and findings from human males or transgenic animals in which the genes coding for these receptors or for aromatase are non-functional, are changing our perception of the roles of oestrogen in the male. Aspects of pubertal development in boys (growth of the long bones, their mineralization and epiphyseal closure) attributed to the actions of androgens are now recognized as being mediated in part by oestrogens. Oestrogens also play a role (probably vasodilatatory) in the cardiovascular system of the male. Within the reproductive system, oestrogens have been shown to play a role in the regulation of fluid resorption from the efferent ducts and appear to be important in the structural and functional development of the Wolffian/excurrent duct system, as well as that of the prostate; inappropriately low or high oestrogen exposure during development can cause permanent changes to these tissues, which may lead to disorders of spermatogenesis and infertility. Sertoli cells and certain germ cells in the testis are also targets for oestrogen action. Many other tissues (adipose, kidney, thymus/immune system, skin, gut and muscle) are oestrogen targets in the male. Based on these findings and the widespread distribution of aromatase, it is argued that many of the effects of oestrogens in the male might stem from its local production and action and, furthermore, that the balance in action between androgens and oestrogens might be of central importance at many oestrogen target sites.
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PMID:The roles of oestrogen in the male. 1840 8

Patients with congenital adrenal hyperplasia arising from mutations of 11beta-hydroxylase, the final enzyme in the glucocorticoid biosynthetic pathway, exhibit glucocorticoid deficiency, adrenal hyperplasia driven by unsuppressed hypothalamo-pituitary-adrenal activity, and excess mineralocorticoid activity caused by the accumulation of deoxycorticosterone. A mouse model, in which exons 3-7 of Cyp11b1 (the gene encoding 11beta-hydroxylase) were replaced with cDNA encoding enhanced cyan fluorescent protein, was generated to investigate the underlying disease mechanisms. Enhanced cyan fluorescent protein was expressed appropriately in the zona fasciculata of the adrenal gland, and targeted knock-out was confirmed by urinary steroid profiles and, immunocytochemically, by the absence of 11beta-hydroxylase. The null mice exhibited glucocorticoid deficiency, mineralocorticoid excess, adrenal hyperplasia, mild hypertension, and hypokalemia. They also displayed glucose intolerance. Because rodents do not synthesize adrenal androgens, changes in reproductive function such as genital virilization of females were not anticipated. However, adult homozygote females were infertile, their ovaries showing an absence of corpora lutea and a central proliferation of disorganized steroidogenic tissue. Null females responded normally to superovulation, suggesting that raised systemic progesterone levels also contribute to infertility problems. The model reveals previously unrecognized phenotypic subtleties of congenital adrenal hyperplasia.
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PMID:Cyp11b1 null mouse, a model of congenital adrenal hyperplasia. 1902 89

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations.
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PMID:Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists. 1922 39

A 29-year-old woman presented with secondary amenorrhea, primary infertility, and virilization, which had developed over the past 2 years was suspected to have a virilizing tumor at her left ovary. Her serum testosterone level was markedly elevated (380 ng/dL). Left salpingoophorectomy was performed, and histopathological examination revealed a thecoma of the left ovary. The postoperative serum testosterone level returned to 65 ng/dL. The patient did not have regression of virilism soon. However, the patient had a normal menstruation 29 days after surgery and gave birth to a baby 13 months after surgery.
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PMID:Ovarian thecoma with virilizing manifestations. 1925 67

Hypogonadism in men is defined as a complex of signs and symptoms due to testosterone deficiency or inappropriate production, which occurs in about 1-2%. Symptoms of hypogonadism depend primarily on the age of the male patients at the time of development of the hypogonadism (pre- or postpubertal). The dominant findings are: impaired puberty, decrease of virilization, infertility or decrease of spermatogenesis, impotence and gynecomastia. Classically hipogonadism is divided into primary (hypergonadotropic) and secondary (hypogonadotropic). The most common causes of primary hypogonadism is Klinefelter's syndrome, while secondary--pituitary tumors. "Peripheral" hypogonadism results from androgen receptor polymorphism. The role of therapy of hypogonadism is to restore or maintain proper spermatogenesis as well as testosterone replacement therapy. Gonadotropin and testosterone therapy is available in treatment of hypogonadism in men. The treatment strategy depends on the age of patient and the goals of therapy (restore of fertility and/or produce and maintain of virilization). The gonadototropins and GnRH are useful in spermetogenesis stimulation. The testosterone replacement therapy is efficacious and safe. Testosterone esters and gels are widely applied.
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PMID:[Pathogenesis, evaluation and treatment of hypogonadism in men]. 1956 24

Mutations in the GnRH receptor gene (GNRHR) can result in hypogonadotropic hypogonadism in humans. Unlike most mammals, mice lack a second form of GnRH (GnRH2) and a type 2 GnRH receptor. To determine whether the GnRH receptor is critical at all stages of reproduction and whether this receptor has additional physiological functions in developing and adult mice, we have generated mice from an embryonic stem cell line containing a retroviral vector with multiple stop codons inserted into intron 1 of the Gnrhr gene. This gene trap insertion resulted in the disruption of exon 2 and exon 3 of the Gnrhr gene. The insertion also contained a lacZ gene that was used as a reporter for GnRH receptor expression in these mice. This model has a similar phenotype to the clinical syndrome of hypogonadotropic hypogonadism. Null Gnrhr mice had small sexual organs, low levels of FSH, LH, and steroid hormones, failure of sexual maturation, infertility, and inability to respond to exogenous GnRH. However, the defective GnRH receptor did not prevent morula/blastocyst development, implantation, masculinization of fetal male mice, or maintenance of early pregnancy. The phenotype of this null Gnrhr mouse was more severe than models in the literature, including the N-ethyl-N-nitrosourea-induced Gnrhr mutant, the kisspeptin (Kiss1) knockout, and the kisspeptin receptor (Gpr54) knockout. In terms of gonadal morphology, adult gene trap-Gnrhr null mice demonstrate a complete cessation of reproduction and serve as an important model for understanding GnRH/GnRHR physiology.
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PMID:Disruption of the single copy gonadotropin-releasing hormone receptor in mice by gene trap: severe reduction of reproductive organs and functions in developing and adult mice. 2006 10


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