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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The X-linked androgen receptor (AR) gene contains two polymorphic trinucleotide repeat segments that code for polyglutamine and polyglycine tracts in the N-terminal trans-activation domain of the AR protein. Changes in the lengths of these polymorphic repeat segments have been associated with increased risk of prostate cancer, an androgen-dependent tumor. Expansion of the polyglutamine tract causes a rare neuromuscular disease, spinal bulbar muscular atrophy, that is associated with low virilization, reduced sperm production, testicular atrophy, and infertility. As spermatogenesis is exquisitely androgen dependent, it is plausible that changes in these two repeat segments could have a role in some cases of male infertility associated with impaired spermatogenesis. To test this hypothesis, we examined the lengths of the polyglutamine and polyglycine repeats in 153 patients with defective sperm production and compared them to 72 normal controls of proven fertility. There was no significant association between the polyglycine tract and infertility. However, patients with 28 or more glutamines (Gln) in their AR had more than 4-fold (95% confidence interval, 4.9-3.2) increased risk of impaired spermatogenesis, and the more severe the spermatogenic defect, the higher the proportion of patients with a longer Gln repeat. Concordantly, the risk of defective spermatogenesis was halved when the polyglutamine tract was short (< or = 23 Gln). Whole cell transfection experiments using AR constructs harboring 15, 20, and 31 Gln repeats and a luciferase reporter gene with an androgen response element promoter confirmed an inverse relationship between Gln number and trans-regulatory activity. Immunoblot analyses indicated that the reduced androgenicity of the AR was unlikely to be due to a change in AR protein content. The data indicate a direct relation between length of the AR polyglutamine tract and the risk of defective spermatogenesis that is attributable to the decreased functional competence of AR with longer glutamine tracts.
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PMID:Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. 936 May 40

Technical advances in magnetic resonance imaging (MRI), notably in high-resolution MRI, have opened up new diagnostic applications in male pelvic pathology. A major indication is the preoperative staging of prostate cancer, where MRI is more reliable than other imaging modalities in differentiating between localized and advanced disease. In monitoring local recurrence after radical prostatectomy MRI is also valuable in differentiating scar tissue from new growth. In benign prostate disease, MRI effectively displays the congenital cysts that may be associated with infertility. Other disease, however - notably benign prostatic hyperplasia - is generally an incidental finding. Ultrasound remains the imaging modality of choice for evaluation of pathologies of the penis, testis and scrotum, e. g. in differentiating malignant from benign scrotal masses or in diagnosing acute scrotum due to testicular torsion or rupture. In isolated cases, MRI is also a valuable diagnostic aid in conditions of these organs, e. g. in the preoperative localization of ectopic testes in cryptorchidism or if US findings are equivocal.
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PMID:CT and MRI of the male genital tract: radiologic-pathologic correlation. 993 74

Some pathologies of the pituitary-gonadal function have recently been found to be due to mutations of the gonadotropin or gonadotropin receptor genes. Although these conditions are extremely rare, they are very informative, by elucidating some less well characterized facets of normal gonadotropin function and the molecular pathogenesis of disturbances in sexual differentiation and fertility. In contrast, there is a common polymorphism in the Luteinizing Hormone (LH) beta-subunit gene, where two point mutations cause two alterations in the amino acid sequence (Trp8 --> Arg and Ile15 --> Thr) and introduce an extra glycosylation signal to Asn13. The carriers of this variant gene are largely healthy, but certain mild differences in their gonadal function have been found, as reflected by alterations in gonadal steroidogenesis, pubertal development and predisposition to diseases such as infertility, polycystic ovarian syndrome, and breast and prostatic cancer. The purpose of this chapter is to review the current knowledge of the occurrence, special functional features and clinical correlates of this LH variant.
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PMID:Alterations in gonadal steroidogenesis in individuals expressing a common genetic variant of luteinizing hormone. 1041 3

Considerable advances have occurred in the sonographic imaging of small parts over recent years, including improved transducer technology and Doppler imaging. After reviewing briefly prostatic anatomy, including McNeal's concept of zonal anatomy, the techniques used for examining the prostate gland sonographically and for performing biopsy are discussed. Ultrasound (US) findings in the normal gland, in benign prostatic hyperplasia, and in prostatic cancer are described, with an emphasis on cancer. The role of targeted and random biopsy is assessed, as is the role of color Doppler in detecting prostatic cancer. An overview of the findings in inflammation and infertility also is provided. The technique used for examining the scrotum and testicles is discussed after a short review of scrotal anatomy. The sonographic appearances of the normal scrotal contents are described, followed by a discussion of findings in tumors, inflammatory conditions, and testicular torsion. A synopsis of the appearances of cysts and microlithiasis also is provided. Both the increased use and expectations by surgeons of US in the assessment of the prostate and testicles make it imperative to understand the techniques, range of findings, new developments, and limitations involved in using this modality.
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PMID:Ultrasound of the prostate and testicles. 1063 47

Hyperandrogenism is currently thought to be central to the pathogenesis of polycystic ovarian syndrome (PCOS), a common endocrine disorder in premenopausal women characterized by irregular menstruation and anovulatory infertility. Although hyperandrogenism is characteristic, some women with PCOS have normal serum androgen levels. All androgens act through the X-linked androgen receptor (AR), the N-terminal domain of which contains a polyglutamine tract encoded by a highly polymorphic CAG trinucleotide repeat tract. Recently, variations in this CAG microsatellite tract, while remaining within the normal polymorphic range (11-38 CAGs), have been inversely correlated with receptor activity. Thus, short tracts are associated with high intrinsic AR activity and increased severity and earlier age of onset of the androgen-regulated tumor prostate cancer, whereas longer CAG tracts are associated with low AR activity and oligospermic infertility. To investigate the role of the CAG repeat tract in PCOS, we measured its length in 91 patients with ultrasound diagnosis of polycystic ovaries, irregular menstrual cycles, and anovulatory infertility and compared them to 112 control subjects of proven fertility with regular menses. Fluorescent-labeled DNA fragments containing the CAG repeat tract were amplified from leucocytic DNA, and their lengths were compared with internal size markers on an automated DNA Sequencer. There were no differences in the mean CAG length between patients and controls when both alleles were considered together or separately. Because there is a subset of PCOS patients whose serum androgens are normal, we compared differences in CAG length between patients whose serum testosterone (T) levels were below the normal laboratory mean, to those that were higher. There was a trend for a lower mean CAG biallelic length among anovulatory patients with T less than 1.73 nmol/L compared with those whose T was more than 1.73 nmol/L (22.47 +/- 0.36 vs. 23.25 +/- 0.29). This difference in CAG length between patients with low and high T levels (20.38 +/- 0.51 vs. 21.98 +/- 0.29) was highly significant (P = 0.004) when only the shorter allele of each individual was considered. Ethnic differences were also evident in our data; Indian subjects had a significantly shorter AR-CAG length compared with Chinese, being 22.08 +/- 0.50 and 23.16 +/- 0.17, respectively. Our data indicate an association between short CAG repeat length and the subset of anovulatory patients with low serum androgens, suggesting that the pathogenic mechanism of polycystic ovaries in these patients could be due to the increased intrinsic androgenic activity associated with short AR alleles.
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PMID:Androgen receptor gene CAG trinucleotide repeats in anovulatory infertility and polycystic ovaries. 1099 52

Androgens are important steroid hormones for expression of the male phenotype. They have characteristic roles during male sexual differentiation, during development and maintenance of secondary male characteristics, and during the initiation and maintenance of spermatogenesis. The two most important androgens in this respect are testosterone and 5 alpha-dihydrotestosterone. Each androgen has its own specific role during male sexual differentiation, testosterone is involved in the development and differentiation of Wolffian duct derived structures, whereas 5 alpha-dihydrotestosterone, a metabolite of testosterone, is the active ligand in the urogenital sinus and tubercle and their derived structures. The actions of androgens are mediated by the androgen receptor. This ligand dependent transcription factor belongs to the superfamily of nuclear receptors, including those for the other steroid hormones. The androgen receptor gene is located on the X-chromosome at Xq11--12 and codes for a protein with a molecular mass of approximately 110 kDa. Only one androgen receptor cDNA has been identified sofar, despite two different ligands. It is generally accepted that defects in the androgen receptor gene prevent the normal development of both internal and external male structures in 46, XY individuals. The end-organ resistance to androgens has been designated as androgen insensitivity syndrome (AIS) and is distinct from other forms of male pseudohermaphroditism like 17 beta-hydroxy-steroid dehydrogenase type 3 deficiency, leydig cell hypoplasia due to inactivating LH receptor mutations or 5 alpha-reductase type 2 deficiency. Furthermore, two additional pathological situations are associated with abnormal androgen receptor structure and function -- spinal and bulbar muscular atrophy (SBMA, or Kennedy's disease) and prostate cancer. In the AR gene, four different types of mutations have been detected in DNA from individuals with AIS -- (i) single point mutations resulting in amino acid substitutions or premature stopcodons; (ii) nucleotide insertions or deletions most often leading to a frame shift and premature termination; (iii) complete or partial gene deletions; and (iv) intronic mutations in either splice donor or acceptor sites, which affect the splicing of AR RNA. The main phenotypic characteristics of individuals with the complete androgen insensitivity syndrome (CAIS) are, female external genitalia, a short, blind ending vagina, the absence of Wolffian duct derived structures, the absence of a prostate, development of gynecomastia and the absence of pubic and axillary hair. Usually testosterone levels are elevated at the time of puberty, while also elevated LH levels are found. In the partial androgen insensitivity syndrome (PAIS) several different phenotypes are evident, ranging from individuals with predominantly a female appearance to persons with ambiguous genitalia, or individuals with a predominantly male phenotype. At puberty, elevated LH, testosterone and estradiol levels are observed. Individuals with mild symptoms of undervirilization (mild androgen insensitivity syndrome (MAIS)) and infertility have been described as well. Phenotypic variation between individuals in different families has been described for several mutations. However, in cases of CAIS no phenotypic variation has been described within one single family, in contrast to families with individuals with PAIS. In general AIS, can be routinely analyzed and more than 150 different mutations have been reported now. Differential diagnosis of AIS is possible with syndromes presenting with almost similar phenotypes but with a completely different molecular cause.
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PMID:Molecular basis of androgen insensitivity. 1142 Jan 35

In France, 12 to 15% of couples experience procreation difficulties. A disorder of spermatogenesis (oligospermia, azoospermia) is responsible in 1/3 of cases. These forms of infertility, labelled idiopathic, probably have a genetic component, like microdeletions of the Y chromosome. The normal rate of circulating androgens suggests the implication, in some cases, of an abnormality from the receptor to the androgens (RA) of these male infertilities, whose number remains to be defined. Point mutations on exons of the gene encoding the AR cannot account for all cases of infertility due to idiopathic disorders of spermatogenesis. Expansion of the number of CAG triplets of exon 1 of the AR gene, already demonstrated in a fatal degenerative neuropathy (Kennedy's disease, in which more than 50% of patients are infertile), has been detected in these cases of idiopathic infertility and would be responsible for AR dysfunction. The number of these triplets is also decreased in patients with androgen-dependent prostate cancer. The polymorphism of repetition of CAG triplets would therefore be responsible for fine adjustment of the AR between excessive and insufficient function. ICSI. (Intra-Cytoplasmic Sperm Injection) is currently proposed in these cases of infertility, but the consequences of transmission of these abnormalities to the offspring are unknown.
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PMID:[Idiopathic male infertility and androgen receptors]. 1176 79

Sexually transmitted diseases (STDs) threaten men's reproductive health, but they are preventable. When the means to prevent STDs are unknown, unavailable, unused, or fail, STDs can threaten the health and fertility of both men and their sex partners. Other threats, such as environmental toxins which may affect men's offspring or reduce sperm count and consequently fertility, have not been consistently identified. If these latter threats exist, they may be preventable. Other reproductive system conditions, such as prostate and testicular cancer, may or may not be preventable, but they pose no risk to others. Since the advent of AIDS, greater attention has been focused upon STDs as primary reproductive health threats. STDs, STD-related infertility, how male reproductive health status affects family health, environmental threats to male fertility, prostate cancer, and testicular cancer are discussed.
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PMID:Men's reproductive health risks. 1229 37

Since the last in a series of childbirth education classes discusses contraception, educators must know about various family planning methods. Oral contraceptives (OCs) comprise combined OCs, phasic OCs, and minipills. Combined OCs inhibit secretion of gonadotropin-releasing hormone, which in turn keeps the follicle-stimulating hormone from inducing the ovarian follicle to grow and keeps luteinizing hormones from activating ovulation. They also thicken cervical mucus. Minipills also thicken cervical mucus and render the endometrium unreceptive to fertilized egg implantation. They do not always inhibit ovulation, however. OCs can induce side effects, such as nausea, hypertension, increased risk of atherosclerosis, and fatigue. The IUD prevents pregnancy either by inhibiting implantation of a fertilized egg or by an inflammatory reaction of the endometrium resulting in a release of macrophages which may destroy sperm. The no-longer-produced Dalkon Shield IUD increased the risk of pelvic inflammatory disease and damaged the reputation of other IUDs. Rare IUD complications are uterine perforation, salpingitis, tubal scarring, pelvic inflammatory disease, and infertility. Diaphragms, cervical film, and condoms serve as barriers between the egg and sperm. The main problem with barrier methods is the increased risk of developing toxic shock syndrome. Spermicide increase the effectiveness of diaphragms, cervical caps, and condoms. Vasectomy keeps sperm from arriving at storage sites. Shortterm side effects are swelling, discomfort, and occasional rejoining of the cut ends of the vas. Research hints at a link between vasectomy and prostate cancer. Some complications of tubal ligation are urinary tract infections, accidental electrical burns, and pelvic infections. Natural family planning methods include withdrawal, the rhythm method, and the sypto-thermal method. Controversial injectable contraceptives are Depo-Provera (medroxyprogesterone acetate) and Noristerate (norethisterone enanthate).
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PMID:Birth control update for childbirth educators. 1234 29

The human Y chromosome encodes genes that are essential for male sex determination, spermatogenesis and protection against Turner stigmata. In recent years mutations have been identified in Y-chromosome genes associated with these phenotypes and a series of microdeletions of the long arm of the Y have been defined that are specifically associated with male infertility. In parallel, the discovery of polymorphic markers on the Y, comprising of both slow-mutating binary markers and rapidly-mutating microsatellites, has enabled the high resolution definition of a large number of paternal lineages (haplogroups). These Y-chromosome haplogroups have been extensively used to trace population movements and understand human origins and histories, but recently a growing number of association studies have been performed aimed at assessing the relationship between the Y-chromosome background and Y-linked phenotypes such as infertility and male-specific cancers. These preliminary studies, comparing haplogroup distributions between case and control populations, are promising and suggest an association between different Y-chromosome lineages, sperm counts and prostate cancer. However, we highlight the need to extend these studies to other world populations. Increased sample numbers and a better haplogroup resolution using additional binary markers in association studies are necessary. By these approaches novel associations between Y-chromosome haplotypes and disease may be revealed and the degree to which selection is acting on the human Y chromosome may be determined.
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PMID:Male reproductive function and the human Y chromosome: is selection acting on the Y? 1293 May 68


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