Male Genital Self-Image Scale (MGSIS): Cutoff Point, Cultural Adaptation and Validation of Measurement Properties in Brazilian Men.

BACKGROUND: Concerns about genital self-image (GSI) can influence sexual function and quality of life, and instruments that assess male GSI, such as the Male Genital Self-Image Scale (MGSIS), need to be adapted and validated in different cultures. AIMS: To culturally adapt and validate the measurement properties of MGSIS in Brazilian men, according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline, and to create a cutoff point for satisfaction with male GSI. METHODS: We assessed the validity of content through a committee of experts and cognitive interviews. The internal consistency and test-retest reliability were assessed using Cronbach's α and Intraclass Correlation Coefficient (ICC). We also calculate measurement errors using the Bland and Altman graph. The structural validity was investigated through exploratory and confirmatory factor analysis. The hypothesis test for construct validity was assessed using Spearman correlation from MGSIS with the International Index of Erectile Function (IIEF), Body Appreciation Scale (BAS-2) and Rosenberg Self-Esteem Scale (RSES). To create a cutoff point for satisfaction with the GSI, the item response theory and the classic test theory were used. OUTCOMES: Male's (i) GSI, (ii) sexual function, (iii) body appreciation, and (iv) self-esteem were assessed. RESULTS: In this study, 518 men with a mean age of 33.90 (±13.83) years participated. The Brazilian version of MGSIS demonstrated good content validity and a single factor that explained 64.57% of the variance. Cronbach's α and ICC values were 0.905 and 0.806, respectively. By assessing measurement errors, we found no systematic bias in the sample. MGSIS showed a moderate to weak correlation with IIEF, BAS-2 and RSES. A cut-off point of 23 in the MGSIS total score was found to rate satisfaction with the GSI. CLINICAL TRANSLATION: MGSIS is a valid and reliable measurement instrument for measuring male GSI in Brazil. STRENGTHS AND LIMITATIONS: This study evaluated the measurement properties of MGSIS according to COSMIN, which is a powerful and useful guideline for measurement properties. However, due to the lack of a gold standard for measuring the GSI, we have not assessed the criterion validity. CONCLUSION: MGSIS is valid, reliable and can be useful to assess the GSI and classify the satisfaction with the GSI of Brazilian men. de Arruda GT, da Silva EV, Braz MM. Male Genital Self-Image Scale (MGSIS): Cutoff Point, Cultural Adaptation and Validation of Measurement Properties in Brazilian Men. J Sex Med 2021;18:1759-1767.

A wet dressing for male genital surgery: A phase II clinical trial.

PURPOSE: This study was to confirm the safety and efficacy of BC dressing when used in surgical male wound healing at the urogenital area. METHODS: Open, non-controlled clinical study of phase II. A total of 141 patients, among those children, adolescents and adults with hypospadias (112), epispadias (04), phymosis (13) and Peyronie's disease (12) that had a BC dressing applied over the operated area after surgery. A written informed consent was obtained from all participants. Study exclusion criteria were patients with other alternative treatment indications due to the severity, extent of the injury or the underlying disease. The outcomes evaluated were efficacy, safe and complete healing. The costs were discussed. RESULTS: In 68% patients, the BC dressing fell off spontaneously. The BC was removed without complications in 13% of patients at the outpatient clinic during the follow-up visit and 17% not reported the time of removal. In 3% of the cases, the dressing fell off early. Complete healing was observed between 8th and 10th days after surgery. The BC dressings have shown a good tolerance by all the patients and there were no reports of serious adverse events. CONCLUSION: The bacterial cellulose dressings have shown efficacy, safety and that can be considered as a satisfactory alternative for postoperative wound healing in urogenital area and with low cost.

Does SARS-CoV-2 Affect the Prostate? A Molecular Analysis from a Case Series of COVID-19 Patients.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 that has been spreading worldwide since December 2019. Viral entry into cells requires expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on the surface of the host cell. The male reproductive system, including the prostate, was supposed to be a potential target for SARS-CoV-2 since the presence of ACE and TMPRS2 receptors. This paper investigated for the first time the presence of SARS-CoV-2 mRNA in the prostatic tissue of a patient with active infection. In addition, we searched for the virus in the prostate of five patients after their recovery from COVID-19. The SARS-CoV-2 RNA was not detected in any of the prostate tissues tested even during the acute phase of infection. As case series have limitations, causality cannot be excluded and sporadic evidence of prostatic tissue invasion by SARS-CoV-2 may be detectable.

Characterization of a novel deep-intronic variant in DYNC2H1 identified by whole-exome sequencing in a patient with a lethal form of a short-rib thoracic dysplasia type III.

Biallelic pathogenic variants in DYNC2H1 are the cause of short-rib thoracic dysplasia type III with or without polydactyly (OMIM #613091), a skeletal ciliopathy characterized by thoracic hypoplasia due to short ribs. In this report, we review the case of a patient who was admitted to the Neonatal Intensive Care Unit (NICU) of Indiana University Health (IUH) for respiratory support after experiencing respiratory distress secondary to a small, narrow chest causing restrictive lung disease. Additional phenotypic features include postaxial polydactyly, short proximal long bones, and ambiguous genitalia were noted. Exome sequencing (ES) revealed a maternally inherited likely pathogenic variant c.10322C > T p.(Leu3448Pro) in the DYNC2H1 gene. However, there was no variant found on the paternal allele. Microarray analysis to detect deletion or duplication in DYNC2H1 was normal. Therefore, there was insufficient evidence to establish a molecular diagnosis. To further explore the data and perform additional investigations, the patient was subsequently enrolled in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM). The investigators at the URDC performed a reanalysis of the ES raw data, which revealed a paternally inherited DYNC2H1 deep-intronic variant c.10606-14A > G predicted to create a strong cryptic acceptor splice site. Additionally, the RNA sequencing of fibroblasts demonstrated partial intron retention predicted to cause a premature stop codon and nonsense-mediated mRNA decay (NMD). Droplet digital RT-PCR (RT-ddPCR) showed a drastic reduction by 74% of DYNCH2H1 mRNA levels. As a result, the intronic variant was subsequently reclassified as likely pathogenic resulting in a definitive clinical and genetic diagnosis for this patient. Reanalysis of ES and fibroblast mRNA experiments confirmed the pathogenicity of the splicing variants to supplement critical information not revealed in original ES or CMA reports. The NICU and URDC collaboration ended the diagnostic odyssey for this family; furthermore, its importance is emphasized by the possibility of prenatally diagnosing the mother's current pregnancy.

Immunological effects of thermal injury. I. Inhibition of spermatogenesis in guinea pigs.

PIP: In the present study, controlled burns of 1 testis have induced the formation of testis-specific antibodies in Hartley guinea pigs. The antibodies reacted with autologous as well as homologous testicular extracts. In addition, pathological changes have been noted in the germinal components of the contralateral testis, which were similar to those observed after the induction of experimental allergic orchitis by active immunization with testicular tissue. Results of the study indicate that thermal injury to guinea pig testes can induce an autoimmune response similar to that observed after immunization with autologous or homologous testicular tissue. The antibodies formed were organ-and species-specific against a testicular antigen. Thermal injury may be associated with autoimmunization of the host by the injured organ.^ieng

Basal Cell Carcinoma of the External Genitalia: A Population-Based Analysis.

INTRODUCTION: Basal cell carcinoma (BCC) located on the genitalia is rare; data on the clinicopathologic features and survival outcomes are only available through case reports and small case series studies. PURPOSE: This study aimed to explore the epidemiology and identify the prognostic factors of genital BCCs. METHODS: We queried the 18 registries of the Surveillance, Epidemiology, and End Results database for patients with primary BCCs of the genital skin from 2000 through 2017. The primary endpoint was overall survival (OS) and disease specific survival (DSS). Kaplan-Meier survival analysis was conducted to assess the impact of clinicopathological variables on OS and DSS. Multivariate Cox proportional hazards model was performed to evaluate risk factors for OS. RESULTS: A total of 1,607 cases of genital BCCs were identified. The cohort was composed of 1,352 women (84.1%) and 255 men (15.9%). The median (P25, P75) age of the entire cohort was 73(63-82)years. White patients accounted for 87.2% of the cases. For women and men, the most common site of involvement was the labia majora (89.6%) and scrotum (74.5%), respectively. The majority of patients with genital BCC had localized disease (75.5%). Kaplan-Meier survival analysis showed that female genital BCCs experienced better DSS than men (209.1 months vs 194.8 months); for men, BCCs located on the scrotum had better DSS and OS than those on the penis (P < 0.05 for both endpoints). All patients with distant disease died of disease-specific death, and the average survival time was 8.2 months. Multivariate analysis revealed that age, primary site, and stage were independent determinants of OS for men, while tumor size, histologic subtype, and race were not. For women, factors associated with worse OS included increasing age, tumor size more than 2 cm, and distant disease; factors associated with a decreased risk included "other" and "unknown" races. CONCLUSION: The prognosis of genital BCCs is excellent, while the survival of distant disease is very poor. Despite similar clinicopathologic features and overall survival outcomes, men and women should be treated as two different entities when making survival predictions.

On the taxonomy of the subgenera Cyabarda Karisch, 2013, Idiovulpecula Karisch, 2013 and Paravulpeculella Karisch, 2013 of the genus Cyana Walker, 1854, with descriptions of three new species from africa (Lepidoptera, Erebidae, Arctiinae, Lithosiini).

The identification of the male of Cyana (Cyabarda) torrida (Holland, 1893) is corrected, the male is illustrated for the first time. Cyana suessmuthi Karisch, 2013 is transferred to the subgenus Cyabarda Karisch, 2013, its female adult and female genitalia are illustrated and diagnosed for the first time. A new species Cyana (Cyabarda) nambi sp. nov. similar to C. torrida is described from Uganda. Cyana torrida maculata Karisch, 2013 is upgraded to species rank and transferred to the subgenus Idiovulpecula Karisch, 2013: C. (Idiovulpecula) maculata Karisch, 2013, stat. nov. Two new species of the subgenus Idiovulpecula are described: C. (Idiovulpecula) lowa sp. nov. (Democratic Republic of the Congo) and C. (Idiovulpecula) foya sp. nov. (Liberia). Adults and genitalia of new and related species are illustrated.

Study on moths of the Herminia decipiens complex (Lepidoptera, Erebidae, Herminiinae) with descriptions of three new species.

Asian herminiine moths of the Herminia decipiens complex are revised and five allopatric species are recognized, i.e. Herminia decipiens (Hampson, 1898) in Nilgiri Hills, Khasi Hills, South China, Indochina, Malay Peninsula, H. terminalis (Wileman, 1915) in Taiwan, H. yuksam sp. nov. in East Nepal, Sikkim, H. borneo sp. nov. in Borneo and H. amamioshima sp. nov. in Amami-oshima Is., Shimo-Koshikijima Is. and South Kyushu (Kagoshima). Key to all species is given.

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.

Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pipeline and the Exomiser variant prioritization tool, at an academic children's hospital with an ethnically diverse pediatric patient population. We achieved a 41% molecular diagnostic rate for 66 duo-, quad-, or trio-WES cases, and 28% for 40 singleton-WES cases. Preliminary results were returned to ordering physicians within 1 wk for 12 of 38 (32%) probands with positive findings, which were instrumental in guiding the appropriate clinical management for a variety of patients, especially in critical care settings. The semiautomated and streamlined WES workflow also enabled us to identify novel variants in candidate disease genes in patients with developmental delay and autism and immune disorders and cancer, including ANK2, BPTF, BCL11A, FOXN1, PLAA, ATRX, DNAJC21, and RAD50 Together, we demonstrated the implementation of a streamlined WES workflow that was successfully applied for both clinical and research purposes.

Factores de riesgo asociados a defectos congénitos de genitales externos y gónadas masculinas

Introducción: Los defectos congénitos del tracto urogenital se encuentran entre las anomalías más encontradas en el feto o neonato, lo que da una idea de su extraordinaria importancia clínica, unido a las escasas investigaciones en la provincia Camagüey, sobre factores de riesgo asociados a los defectos congénitos de genitales externos y gónadas masculinas. Objetivo: Determinar los factores de riesgo asociados a defectos congénitos de genitales externos y gónadas masculinas. Métodos: Se realizó un estudio correlacional del tipo retrospectivo en el Hospital Pediátrico Eduardo Agramonte Piña en el periodo de enero de 2013 a diciembre de 2020. El universo se conformó por los 96 pacientes que fueron intervenidos quirúrgicamente por presentar defectos congénitos de los genitales externos y gónadas masculinas. Para determinar la asociación de los factores de riesgo con la aparición de defectos congénitos se empleó la prueba de independencia, en caso de p<0,05 se consideró asociación significativa. Para medir la magnitud de la asociación estadística entre las variables se utilizó el coeficiente Phi, se consideró mientras más fuerte a uno fuera su valor, más correlacionadas se encontraron las variables estudiadas. Resultados: La criptorquidia fue la forma clínica con mayor número de pacientes, seguida de la hipospadias y la hidrocele. La asociación entre los padres trabajadores agrícolas y la hipospadias y la criptorquidia con padres trabajadores industriales, resultaron significativas. El hecho que la madre fuera fumadora pasiva, constituyó una variable con asociación significativa, tanto para la aparición de hipospadias como de criptorquidia. El ser fumadora pasiva fue el factor de riesgo que tuvo mayor correlación con la aparición de los defectos congénitos. Conclusiones: Existieron factores de riesgo con asociación significativa a la aparición de defectos congénitos de genitales externos y gónadas masculinas.

Introduction: Congenital defects of the urogenital tract are among the anomalies most found in the fetus or neonate, which gives an idea of ​​their extraordinary clinical importance, together with the few investigations in the Camagüey province, on risk factors associated with congenital defects of external genitalia and male gonads. Objective: To determine the risk factors associated with congenital defects of the external genitalia and male gonads. Methods: A retrospective correlational study was carried out at the Eduardo Agramonte Piña Pediatric Hospital from January 2013 to December 2020. The universe was made up of the 96 patients who underwent surgery for presenting congenital defects of the external genitalia and male gonads. To determine the association of the risk factors with the appearance of congenital defects, the independence test was used; in case of p<0.05, a significant association was considered. To measure the magnitude of the statistical association between the variables, the Phi coefficient was used, it was considered that the stronger its value was, the more correlated the studied variables were found. Results: Cryptorchidism was the clinical form with the highest number of patients, followed by hypospadias and hydrocele. The association between farm worker parents and hypospadias and cryptorchidism with industrial worker parents was significant. The fact that the mother was a passive smoker was a variable with a significant association, both for the appearance of hypospadias and cryptorchidism. Being a passive smoker was the risk factor that had the highest correlation with the appearance of birth defects. Conclusions: There were risk factors with a significant association with the appearance of congenital defects of the external genitalia and male gonads.

Estrogen exposure during gestation and risk of testicular cancer.

In this case--control study of 108 cases of testicular cancer in men under 30 years of age, cryptorchidism was a major risk factor [relative risk (RR) = 9.0]. Low birth weight was also associated with increased risk (RR = 3.2). Having severe acne at puberty was protective (RR = 0.37). Interviews with mothers of cases revealed that exposure of the mother to exogenous estrogen during pregnancy created a significant risk in the son (RR = 8.0). In first pregnancies, excessive nausea indicated an increased risk of testicular cancer (RR = 4.2). Increased body weight in the mother also increased the risk. The relation between these factors and testicular hypoplasia is discussed. Severe perimenopausal menorrhagia was a factor in the mother associated with reduced risk of testicular cancer in the son (RR = 0.10). A modified hormonal milieu in the mother appears to be important in the later development of testicular cancer in her sons.

Experts confer on vasectomy and prostate cancer risk.

PIP: In March 1993, physicians attended a US National Institutes of Health (NIH) conference on a possible association between vasectomy and prostate cancer. Participants learned that some studies have found an association while others have not. The strongest evidence of an association is a small association. The inconsistency of the results of various studies and the lack of a convincing biological mechanism satisfied participants that no need exists to recommend changes in clinical and public health practice. 2 recent, well-controlled studies, conducted by researchers at Brigham and Women's Hospital in Boston, Massachusetts, published in the Journal of the American Medical Association found around a 60% increase in risk of developing prostate cancer in men with vasectomies. It found a decreased risk for overall mortality among vasectomized men, however. These studies prompted a call for this NIH conference. Studies prior to these Boston studies had methodological flaws, especially detection bias. Specifically, urologists are more likely to examine men with vasectomies and, therefore, diagnose prostate cancer. A well-controlled, large-scale, case control study in California published in 1991 and its follow-up study did not find an increased risk of prostate cancer in vasectomized men. The follow-up study found a decreased risk for overall mortality among men with vasectomies. The lack of knowledge about the etiology of prostate cancer is the biggest roadblock to understanding the link between vasectomy and prostate cancer. Suggested mechanisms explaining vasectomy's ability to increase prostate cancer risk include changes in hormone levels, immunologic responses, and changes in levels of cancer-promoting growth factors or inhibitors of these factors.^ieng

Vasectomy and prostate cancer: results from a multiethnic case-control study.

BACKGROUND: Vasectomy, a widely used form of contraception, has been associated in some studies with increased prostate cancer risk. PURPOSE: We assessed this association on the basis of data collected in a large multiethnic case-control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). METHODS: In home interviews conducted with newly diagnosed prostate cancer case patients and population control subjects, we obtained information on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed, as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of sex hormones and sex hormone-binding globulin. RESULTS: The present analysis was based on 1642 prostate cancer patients and 1636 control subjects. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.83-1.3), whites (OR = 0.94; 95% CI = 0.69-1.3), blacks (OR = 1.0; 95% CI = 0.59-1.8), or Chinese-Americans (OR = 0.96; 95% CI = 0.42-2.2). Among Japanese-Americans, the OR was 1.8 (95% CI = 0.97-3.4), but the statistically nonsignificant elevation in risk was limited to more educated men and those with localized cancers. ORs did not vary significantly by age at vasectomy or years since vasectomy. We found a lower serum concentration of sex hormone-binding globulin and a higher ratio of dihydrotestosterone to testosterone among vasectomized control subjects than among nonvasectomized control subjects. CONCLUSIONS: The findings of this study do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects seen in this cross-sectional comparison warrant further evaluation in longitudinal studies.

PIP: Vasectomy has been associated in some studies with increased prostate cancer risk. This association was assessed on the basis of data collected in a large multiethnic case control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). In home interviews conducted with newly diagnosed prostate cancer case patients (diagnosed between January 1, 1989 and December 31, 1991 as well as January 1, 1987 and December 31, 1988) and control subjects, information was obtained on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of total testosterone, percent of free testosterone, percent of bioavailable testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) using an automated, polyclonal-monoclonal immunochemiluminometric prostate-specific antigen (PSA) assay. The analysis was based on 1642 prostate cancer patients and 1636 control subjects. The analysis of PSA, androgens, and SHBG by vasectomy status was based on 850 control subjects with normal PSA concentrations. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; Whites OR = 0.94; Blacks OR = 1.0; or Chinese-Americans OR = 0.96). Among Japanese-Americans, the OR was 1.8, but the statistically significant elevation in risk (OR = 4.1) was limited to more educated men with a history of vasectomy and those with localized cancers (OR = 5.3). ORs did not vary significantly by age at vasectomy or years since vasectomy. Lower serum concentration of SHBG and a higher ratio of DHT to testosterone was found among vasectomized control subjects than among nonvasectomized control subjects. The findings do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects warrant further evaluation in longitudinal studies.

Are dietary fat and vasectomy risk factors for prostate cancer?

PIP: Prostate cancer is the most commonly diagnosed malignancy among US males. Its incidence, however, varies markedly from 2 per 100,000 per year in Shanghai, China, to 62 and 82, respectively, for US Whites and Blacks. Mortality due to prostate cancer is twice as high among US Blacks than among US Whites. A familial component is important in determining prostate cancer risk, but does not appear to explain the variation in rates between US Blacks and Whites. Dietary fat, the consumption of which varies on a national basis in parallel with prostate cancer rates, may be a major risk factor for the disease. A study by Whittemore et al. involved more than 1500 cases and controls including Whites, Blacks, Chinese-Americans, and Japanese-Americans in five cities in the US and Canada. On the basis of detailed dietary interviews, Whittemore shows that prostate cancer risk increases with higher intake of saturated fat. The effect holds true for both younger and older men. The risk was significantly elevated for Asian-Americans, and less pronounced for Blacks and Whites, yet nonetheless consistent with an overall excess. Risk was unrelated to the intake of other macronutrients, intake of vitamin A, intake of fruits and vegetables, body mass, or physical activity. Among Asian-Americans, long-term residents in the US were at greatest risk of prostate cancer independent of dietary fat intake. A study by John et al. has found vasectomy to not be related to the development of prostate cancer. Reasons why the finding of this study is opposite from the general body of evidence supporting an increased risk of prostate cancer following vasectomy are not apparent.^ieng

Vasectomy linked to increased risk for prostate cancer.

PIP: 2 case control studies conducted at Brigham and Women's Hospital in Boston, Massachusetts, showed an increased risk of developing prostate cancer in men who had undergone a vasectomy. The prospective study followed 37,800 nonvasectomized men and 10,055 vasectomized men between 1986 and 1990 and revealed a 66% increased risk of prostate cancer among vasectomized men. This increased risk was even greater in men who had had a vasectomy at least 22 years earlier (85%). A retrospective study examined 14,607 vasectomized men and 14,607 nonvasectomized men and found a 56% increase in prostate cancer risk. Like to prospective study, the risk as higher after 20 years (89%). Most other studied examining an association between vasectomy and prostate cancer had small numbers of subjects. They found either no association or a weak association. One study did have large numbers, however. In this study, researchers followed 5332 vasectomized cases and 15,996 nonvasectomized controls for almost 7 years and did not find an increased risk for prostate cancer. Nevertheless, the chief investigator of the case control studies emphasized that cumulative epidemiologic data, the apparent absence of bias and confounding, and the effect vasectomy has a prostatic function and the immune system suggest a causal link. An epidemiologist at the National Cancer Institute cautions, however, that, even though the findings from these studies are important, the biologic basis for a causal connection is not known, thus, further studies are needed. The increased risk of prostate cancer in men who had a vasectomy more than 20 years age or were 40 year old at time of vasectomy suggests that physicians should conduct an annual digital rectal exam and determine the serum prostate specific antigen level in these men. The retrospective study did not find an increase overall death rate in vasectomized men and neither study found an increase risk of death from prostate cancer after vasectomy.^ieng

Distinct testicular 17-ketosteroid reductases, one in interstitial tissue and one in seminiferous tubules. Differential modulation by testosterone and metabolites of testosterone.

The final step in the biosynthesis of testosterone is the reduction of androstenedione, which is catalyzed by the microsomal enzyme 17-ketosteroid reductase. Evidence is presented which suggests that there are two distinct 17-ketosteroid reductases in rat testes, one in interstitial tissue and one in seminiferous tubules. The two enzymes have different pH optima, 5.6 for the one from interstitial tissue and 6.5 for the one from seminiferous tubules. At the optimum pH, a 70-fold difference in Km values was observed, 17 muM for the interstitial tissue enzyme and 0.25 muM for the enzyme from seminiferous tubules. Testosterone and metabolites of testosterone have very different effects of each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several 5alpha-reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5alpha-androstane-3alpha, 17beta-diol, followed by 17beta-estradiol approximately equal to dihydrotestosterone greater than testosterone greater than estrone greater than estriol. 5alpha-Androstane-3alpha, 17beta-diol and 17beta-estradiol were shown to act by competitive inhibition with apparent Ki values of 2.2 and 3.7 muM, respectively. In contrast, it was demonstrated that among the above steroids, only dihydrotestosterone inhibits the 17-ketosteroid reductase activity of seminiferous tubules and this inhibition was only observed at very high concentrations of inhibitor. Testosterone stimulated the 17-ketosteroid reductase activity of seminiferous tubules. 5alpha-Androstane-3alpha, 17beta-diol at low concentrations stimulated the enzyme activity from seminiferous tubules, while it had no effect at high concentrations. The remainder of the steroids tested had no effect on the 17-ketosteroid reductase activity of seminiferous tubules. The difference in response of the two enzyme activities suggests a mechanism for local regulation of testosterone synthesis in each testicular compartment that does not involve directly pituitary gonadotropins.

PIP: 2 distinct 17-ketosteroid reductases, 1 in interstitial tissue and the other in the seminiferous tubules, were identified in rat testes and characterized. The pH optima was 5.6 for the interstitial tissue enzyme and 6.5 for the seminiferous tubule enzyme. At optimum pH, K m values for the interstitial tissue enzyme was 17 mcM while that for the seminiferous tubule enzyme was .25 mcM. Testosterone, several 5alpha-reduced testosterone metabolites, and estrogens inhibited interstitial tissue enzyme activity, with 5alpha-androstane-3alpha, 17beta-diol being the most potent inhibitor, followed by 17beta-estradiol and dihydrotestosterone, testosterone, estrone, and estriol. 5alpha-androstane-3alpha, 17beta-diol and 17beta-estradiol were found to act by competitive inhibition. Of the above steroids, only dihydrotestosterone was able to inhibit enzyme activity in the seminiferous tubules, and then at only very high concentrations of the androgen. 17-ketosteroid reductase activity in seminiferous tubules was stimulated by testosterone and low concentrations of 5alpha-androstane-3alpha, 17beta-diol. The results suggest an extrapituitary mechanism for the local regulation of testosterone synthesis in interstitial tissue and the seminiferous tubules.

Genital ulceration as a risk factor for human immunodeficiency virus infection.

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

The influence of progesterone on the conversion of 17-hydroxyprogesterone to testosterone in the mouse testis.

PIP: Tritiated-progesterone and 17-hydroxyprogesterone-carbon 14 were incubated with mouse testis homogenates obtained from adult Swiss mice. The distribution of each isotope in 17-hydroxyprogesterone, androstenodione and testosterone when the 2 precursors were present in various ratios were compared with the amounts when each precursor was present alone. Formation of the major compound in these experiments occurs by a series of sequential reactions: progesterone to 17-hydroxyprogesterone to androstenodione to testosterone, and the assumption is made that the sum of the products beyond a given enzymatic step equals the amount of a particular precursor undergoing that reaction. The presence of equal amounts of progesterone and 17-hydroxyprogesterone caused a small but significant reduction in 17-hydroxyprogesterone activity. The presence of added 17-hydroxyproesterone essentially did not affect the rate at which 17-hydroxyprogesterone or 17-oxy radical formed from progesterone, but the amount of C-19 steroids progressively decreased as progesterone concentration was raised above 2.5 nmales per ml. This was probably because of the close association of active sites of the 17-hydroxylase and lyase. The presence of progesterone markedly inhibited the rate of splitting of the added 17-hydroxyprogesterone. The inhibition was probably competitive as previously reported for rat testis. The results indicate that the active site of the 17-beta-dehydrogenase was not closely associated with the lyase. At higher levels of either precursor alone the 17-beta-dehydrogenase approached saturation, but the inhibition of lyase activity by progesterone left the 1-beta-dehydrogenase unsaturated and a higher proportion of the smaller amounts of androstenodione formed was converted to testesterone.^ieng

Testicular chromosomal mosaicism and infertility.

A healthy young man with azoospermia and no other endocrinological abnormalties was shown to have chromosomal mosaicism with the cytogenetic errors found only in testicular tissue. Three clones of cells were identified in both meiosis I and meiosis II by cytogenetic analysis of direct testicular smears. Peripheral blood karyotypes and buccal smear preparations revealed no abnormalities. It is postulated that the gonadal cytogenetic defects account for this patient's azoospermia. In addition, it is hypothesized that this type of incomplete spermatogenesis nonetheless produces sufficiet feedback material ("inhibin") so that FSH levels are not affected.

PIP: The study of a patient with testicular chromosomal mosaicism and inf ertility is reported. A healthy 27-year-old man with azoospermia and no other endocrinological abnormalities was shown to have chromosomal mosaicism with the cytogenetic errors found only in testicular tissue. 3 clones of cells were identified in both meiosis 1 and meiosis 2 by cytogenetic analysis of direct testicular smears. No abnormalities were revealed in peripheral blood karyotypes or buccal smear preparations. It is postulated that the gonadal cytogenetic defects account for the azoospermia in this patient and that this type of incomplete spermatogenesis produces sufficient feedback material ("inhibin") so that follicle stimulating hormone levels are not affected.

Human seminal plasma contains a protein that shares physicochemical and immunochemical properties with placental protein 5 from the human placenta.

Placental protein 5 (PP5)-like immunoreactive material was detected in human seminal plasma at high concentrations (32-1000 ng/ml). This was not due to interference with proteases or binding to seminal plasma proteins, since immunoreactivity was not affected by treatment with protease inhibitors, and incubation with seminal plasma of [125I]PP5 did not bring about any significant change in the elution pattern in gel filtration. Part of the PP5 immunoreactivity in seminal plasma had a molecular weight of 36,000-42,500 which is the molecular weight of purified PP5 from the human placenta. In RIa, serial dilutions of the 36,000-42,500 molecular weight material gave an inhibition curve parallel to that of the PP5 standard. The source of seminal plasma PP5-like material is not from the testes, as the levels in vasectomized men were similar to those in nonvasectomized men.