The relationship between dioxins exposure and risk of prostate cancer with steroid hormone and age in Vietnamese men.

Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly injurious to health, not all causal relationships have been clarified. We therefore explored associations among dioxins, steroid hormones, age and prostate cancer risk in men. We compared serum levels of dioxin, steroid hormones and prostate specific antigen (PSA) in men aged 56-81years from herbicide-exposed hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of dioxin congeners in the hotspot group were 1.5-11.3 times higher than the non-sprayed group depending on specific compound. Levels of testosterone, estradiol and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activity in the hotspot group were also significantly higher than in non-sprayed group. Estradiol levels were significantly related to levels of several specific dioxin derivatives in both group. Significant positive correlations were also found between DHT and 1234678-HpCDD or 1234678-HpCDF; and between 3ß-HSD activity and 123678-HxCDD, 123478-HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and tobacco use, multiple linear regressions showed levels of dihydrotestosterone (DHT), estradiol, testosterone and 3ß-HSD activity were not associated with dioxins in the two groups; however, levels of DHT, testosterone and 3ß-HSD activity increased significantly with age in the hotspot group. The hotspot and non-sprayed groups did not significantly differ in PSA levels. But six of the hotspot subjects had PSA levels >3ng/mL, 3 of whom were suspected to have prostate cancer (PC) after digital rectal examination. Our findings suggest that dioxin exposure can lead to increased levels of several sex steroid hormones with age. The correlation of dioxin with steroid hormone levels and prostate cancer risk should be studied further.

Influence of standing estrus before an injection of GnRH during a beef cattle fixed-time AI protocol on LH release, subsequent concentrations of progesterone, and steriodogenic enzyme expression.

Beef cows that exhibit estrus before fixed-time AI have been reported to have increased pregnancy success and increased concentrations of progesterone during the subsequent estrous cycle. Therefore, these experiments were conducted to evaluate if initiation of standing estrus before an injection of GnRH during a fixed-time AI protocol affected LH pulses, subsequent concentrations of progesterone, and luteal steroidogenic enzyme expression. In Experiments 1 and 2, cows were treated with the CO-Synch protocol (100 µg GnRH day -9, 25 mg PGF(2α) day -2, and 100 µg GnRH day 0) and allotted to one of two treatments: 1) cows that initiated estrus before GnRH on day 0 (estrus; n = 5) or 2) cows that did not initiate estrus and were induced to ovulate by the GnRH on day 0 (no estrus; n = 5). In Experiment 1, blood samples were collected at 15-min intervals from 0 to 6 (bleed 1), 12 to 20 (bleed 2), 26 to 34 (bleed 3), and 40 to 48 (bleed 4) h after GnRH. Daily blood samples were collected for 17 d. Initiation of estrus before the GnRH injection had no effect on LH release or the pattern of progesterone increase; however, cows detected in estrus had overall increased (P = 0.002) concentrations of progesterone compared with cows not in estrus. In Experiment 2, estrus was detected with the HeatWatch system. Location and size of the ovulatory follicle was determined on day 0 by transrectal ultrasonography at time of injection with GnRH. Blood samples were collected on days 3, 4, 5, 7, and 9; luteal tissue was collected on day 10 (n = 4 estrus and n = 9 no estrus) from corpus luteum (CL) originating from similar-sized follicles (13.0 to 16.0 mm). Total cellular RNA was extracted, and relative mRNA levels were determined by real-time reverse transcription PCR and corrected for GAPDH. There was no effect of estrus on CL weight or concentrations of progesterone. In addition, there was no effect of estrus, follicle size, or CL weight on luteal expression of LH receptor, StAR, CYP11A1, or 3ßHSD. However, there was a correlation between follicle size and CL weight (P = 0.01; R(2) = 0.43); for every increase of 1 mm in follicle size, CL weight increased by 1.5 g. In summary, estrus did not influence release of LH, CL weight, progesterone concentrations, or expression of steriodogenic enzymes. However, as follicle size increased, CL weight increased; therefore, both follicle size and CL weight were associated with progesterone concentrations.

Polymorphisms in steroidogenesis genes, sex steroid levels, and high myopia in the Taiwanese population.

PURPOSE: To evaluate the relationship among single nucleotide polymorphisms (SNPs) in steroidogenesis enzyme genes, serum levels of sex steroids, and high myopia in Taiwanese male and female populations. METHODS: A campus-based sample of 283 cases (145 males and 138 females) with high myopia and 280 controls (144 males and 136 females) with low myopia or emmetropia was studied. Estradiol, progesterone, and testosterone levels were determined using enzyme-linked immunosorbent assay kits. We genotyped six SNPs within five steroidogenesis enzyme genes (17 alpha-hydroxylase/17,20 lyase [CYP17A1], 3 beta-hydroxysteroid dehydrogenase [HSD3B1], 17 beta-hydroxysteroid dehydrogenase 1 [HSD17B1], steroid-5-alpha-reductase, alpha polypeptide 2 [SRD5A2], and aromatase [CYP19A1]) using polymerase chain reaction-restriction fragment length polymorphism methods. Student's t-tests, χ(2) tests, logistic regression, multifactor dimensionality reduction (MDR) methods, and ANOVA were used to determine significance. RESULTS: An MDR analysis corroborated the synergistic genotype association and demonstrated that synergistic interaction between rs6203 (HSD3B1), rs10046 (CYP19A1), and sex might confer susceptibility to high myopia (p=0.019). In both male and female subjects, levels of testosterone were significantly higher in cases than in controls; in male subjects, the levels of estradiol were significantly higher and those of progesterone were significantly lower in cases (all p-values <0.001). The rs605059 (HSD17B1), with sex-gene interaction, showed association with estradiol levels in males (p=0.035) and testosterone levels in females (p=0.027). CONCLUSIONS: Testosterone levels correlate with high myopia, and interaction of steroidogenesis enzyme genes and sex may be a modulating factor in sex hormone metabolism and high-myopia risk.

SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness.

BACKGROUND: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.

Sterilization of male stray dogs with a single intratesticular injection of calcium chloride: a dose-dependent study.

OBJECTIVE: To study a method of chemical sterilization and its efficacy in adult male stray dogs. METHODS: Sterilization was performed 45 days after a single bilateral intratesticular injection of calcium chloride (CaCl(2)) at the doses of 5, 10, 15 or 20 mg per testis per kg body weight. RESULTS: Histomorphological measures of testes showed total necrosis of testicular tissue at 45 days after an injection of either 10 or 15 or 20 mg CaCl(2) along with fibrosis and hyalinization in seminiferous tubules and interstitial spaces. Infiltration of leucocytes was also observed with the 10- or 15-mg dose. Disintegration of germ cell arrangement in seminiferous tubules and washing out of germ cells from the tubules were noted with the 5-mg dose. Relative organ weight, epididymal sperm count, plasma and intratesticular concentrations of testosterone, testicular activities of Delta(5),3beta-hydroxysteroid dehydrogenase (Delta(5),3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and superoxide dismutase (SOD) and testicular contents of glutathione (GSH) and glutathione disulphide (GSSG) and the ratio of GSH/GSSG, all were declined in each of the calcium chloride treated groups in comparison to the control group. Increases occurred in testicular malondialdehyde (MDA) and plasma concentrations of LH and FSH with each of the treatments by comparison with the control group. Plasma concentrations of cortisol, fasting blood sugar level, blood urea nitrogen as well as packed cell volume (PCV) and total plasma protein were recorded to monitor the changes in chronic stress in the experimental animals. Changes in these parameters were not significant. CONCLUSION: An intratesticular injection of CaCl(2) at specified doses could be a suitable method of sterilization in preference to surgical castration of dogs.

Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess.

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs. DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients. MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH-stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher activity of delta(5)17-OH, compared with PCOS patients without AA excess. CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater delta(5)17-OH activity in response to ACTH.

[Abnormalities of adrenal steroidogenesis in Chilean boys with micropenis]. / Anomalías de la esteroidogénesis suprarrenal en niños chilenos con micropene.

BACKGROUND: Mutations in type II 3 beta hydroxysteroid Dehydrogenase (3 beta HSD) are found in male children with severe undervirilized genitalia. Mild undervirilization (isolated micropenis or with distal hypospadia) can be associated with a partial deficit in 3 beta HSD activity. AIM: To assess the frequency of abnormal adrenal response to ACTH, suggesting a deficit in adrenal enzymatic activity, in children with mild undervirilization. PATIENTS AND METHODS: We studied 26 male children with micropenis, aged one to eight years. Children with evidences of puberal development or in treatment with drugs that affect steroidal metabolism were excluded from the study. Serum levels of androstenedione (A), dehydroepiandrosterone (DHEA), progesterone (P), 17 hydroxyprogesterone (17 P) and the ratios DHEA/A, P/17 P, 17 P/DHEA were measured after an adrenal stimulation with 0.25 mg/m2 intramuscular ACTH. RESULTS: Two children had DHEA y DHEA/A values suggesting a defective 3 beta HSD activity. Other two children had high levels of 17 P, suggesting a deficiency of cytochrome p450c21. A CYP 21 gene mutation was found in one of the later children. CONCLUSIONS: A low proportion of children with micropenis have a deficient 3 beta HSD activity.

Age-related differences in corticosterone secretion in female rats.

The effects of age on steroidogenesis in rat zona fasciculata-reticularis (ZFR) cells were studied. Young, adult, and middle-aged rats were ovariectomized (Ovx) and received replacement therapy with oil or estradiol benzoate ([EB] 25 microg/mL/kg). Rat ZFR cells were incubated with corticotropin (ACTH), prolactin (PRL), or forskolin at 37 degrees C for 1 hour. The effects of age on the activity of steroidogenic enzymes of ZFR cells were measured by the amount of intermediate steroidal products separated by thin-layer chromatography. Plasma levels were higher for PRL (54% to 254%) and corticosterone (179% to 257%) in middle-aged versus young rats. In oil-treated Ovx rats, basal and ACTH-stimulated corticosterone release by ZFR cells were also greater in middle-aged compared with young rats. Replacement with EB in Ovx rats increased the ACTH-stimulated release of corticosterone. Administration of ovine PRL in vitro resulted in a dose-dependent increase of corticosterone production. In oil-treated middle-aged rats, ovine PRL-stimulated corticosterone release was higher than in young rats. Forskolin-induced production of cyclic adenosine 3',5'-monophosphate (cAMP) was greater in middle-aged versus young rats and correlated with the increase of corticosterone production. The activity of steroidogenic enzymes in rat ZFR cells was unchanged by age. These results suggest that the age-related increase of corticosterone production in female rats is associated with the stimulatory effect of PRL on ZFR cells and is due in part to an increase of cAMP generation.

Nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency: a review of our experience with 25 female patients.

OBJECTIVE: To report 15 new menarcheal women affected with nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency (nonclassical 3 beta-HSD) and evaluation of glucocorticoid therapy in treated patients. DESIGN: Diagnosis of these new patients using a standard adrenocorticotropin test. Effects of glucocorticoid therapy on clinical hormonal and sonographic features of each patient are appreciated for periods varying between 4 months and 7 1/2 years. SETTING: All at The New York Hospital-Cornell Medical Center. The Pediatric Endocrinology Ambulatory Service; the Children's Clinical Research Center Core Laboratories; and the Department of Radiology. PATIENTS, PARTICIPANTS: Fifteen menarcheal women (14 to 30 years of age) newly diagnosed and 10 women previously diagnosed were evaluated for symptoms of hyperandrogenism and/or irregular menses. MAIN OUTCOME MEASURE(S): Positive effect of glucocorticoid therapy on signs and symptoms, hormonal levels, and ovarian imaging. RESULTS: Polycystic ovarian syndrome is noted in approximately half the cases. Glucocorticoid treatment greater than 3 months duration results in a reversal of symptoms in most cases.

[Morphological and endocrinological study of theca cell tumor during pregnancy].

With a theca cell tumor of the ovary associated with pregnancy, an extremely rare occurrence in a 30 years old primigravida at 15 weeks of gestation, morphological and endocrinological studies were performed. The tumor was composed of cell-nests scattered among a fibromatous structure. The round or polygonal cells are rich in eosinophilic cytoplasm, resembling theca internal cells. The histochemical activity of 3 beta-HSD and G-6-PDH was demonstrated in these cells. They had the ultrastructures characteristic for steroid-producing cells, in some of which immature and mature Reinke crystalloid-like structures were identified. Mature ones were infrequently observed in contrast to the numerous immature ones. It is considered that a few cells might have differentiated into Leydig cells in the course of differentiation into thecomatous cells from ovarian stroma or mesenchyme. Judged from the rapid enlargement in early pregnancy, this tumor may depend on hCG. Serum estradiol was decreased immediately after removal of the tumor even at 15 weeks of gestation. Histochemical, ultrastructural and endocrinological findings suggest that the tumor was secreting mainly estradiol at the time of the operation.