This article reported the clinical characteristics and SRD5A2 gene mutation pattern of a child with steroid 5-α reductase type 2 deficiency. The 2-month-old boy showed hypospadias and short penis shortly after birth. DNA was extracted from the peripheral blood of the child and his parents. The endocrine disease-related genes were captured and sequenced by high-throughput sequencing technology, and the family DNA samples were verified by Sanger sequencing. The results showed that c.680G>A(p.R227Q) and c.608G>A(p.G203D) compound heterozygous mutations existed in the SRD5A2 gene of the child. The c.680G>A mutation inherited from his father, which was a known pathogenic mutation. The c.608G>A mutation originated from his mother, which was a novel mutation discovered in this study. These results provide molecular evidence for the etiological diagnosis of the child and genetic counseling for the family, as well as extend the mutation spectrum of SRD5A2 gene.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; genetics ; Base Sequence ; Child ; Female ; Humans ; Hypospadias ; Infant ; Male ; Membrane Proteins ; genetics ; Mutation

OBJECTIVESTo study the changes of sexual gland 5 alpha-reductase type II activity in pubertal and adult rats with diabetes.

METHODSWe selected 40 and 90 days old male Wistar rats as pubertal and adult animal model respectively, 30 rats in each group. The rats were randomly divided into three groups: control group (C), diabetic group (D) and diabetes with insulin replacement group (ID). The activity of 5 alpha-reductase type II was measured with thin layer chromatography in the epididymis, prostate and testis.

RESULTS1. In all sexual glands of pubertal rats, the activity of 5 alpha-reductase type II in D group is significantly lower than that in C and ID groups. 2. In all sexual glands of adult rats. there is no difference in the activity of 5 alpha-reductase type II among these groups.

CONCLUSIONSThe activity of 5 alpha-reductase type II is likely to be influenced by metabolic environment, hormonal levels and local specific factors in pubertal rats, but it is relatively stable in adult rats.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; enzymology ; Epididymis ; enzymology ; Male ; Prostate ; enzymology ; Rats ; Rats, Wistar ; Testis ; enzymology

ObjectiveTo explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer .

METHODSData about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed.

RESULTSTotally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05).

CONCLUSIONSSRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; metabolism ; Data Mining ; Humans ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Prostatic Neoplasms ; enzymology ; mortality ; pathology ; surgery ; Prostatic Neoplasms, Castration-Resistant ; enzymology

PURPOSE: Vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis and microvessel density (MVD), which is an important indicator of neoangiogenesis, were independently evaluated to elucidate the mechanism of decreased bleeding observed in patients treated with finasteride, an inhibitor of 5alpha-reductase (5AR). We evaluated MVD and the expression of VEGF and 5AR type II in patients with benign prostatic hyperplasia (BPH) treated with finasteride. MATERIALS AND METHODS: The study included 61 patients undergoing transurethral prostatectomy (TURP) for BPH. Among these patients, 29 had well-preserved paraffin blocks, 13 of whom were given finasteride for a minimum of 3 weeks before surgery; the remaining 16 patients served as controls. MVD was calculated by counting the number of positively stained blood vessels on 5 random, high-power fields within the prostatic section. Expressions of VEGF and 5AR type II were analyzed with a confocal laser scanning microscope and an image analyzer. RESULTS: Prostatic MVD was significantly lower in the finasteride-treated group (p<0.05). The expression of VEGF and 5AR type II at the level of the prostatic glandular epithelium and stroma was not significantly different between the 2 groups. VEGF and 5AR type II were more strongly expressed in the epithelium of both groups than in stromal smooth cells (p<0.05). CONCLUSIONS: Finasteride treatment had no clear effect on the expression of VEGF or 5AR type II. It is possible, however, that finasteride improves blood loss after TURP and BPH-induced hematuria by reducing MVD. Further study on the mechanism of MVD reduction is needed.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; Blood Vessels ; Epithelium ; Finasteride ; Hematuria ; Hemorrhage ; Humans ; Microvessels ; Paraffin ; Prostatic Hyperplasia ; Transurethral Resection of Prostate ; Vascular Endothelial Growth Factor A

3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child, Preschool ; DNA Mutational Analysis ; Disorder of Sex Development, 46,XY/genetics* ; Female ; Humans ; Membrane Proteins/genetics* ; Mutation

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with 5α-reductase type 2 deficiency. METHODS: Clinical data of the child was retrospectively analyzed. Targeted capture-next generation sequencing and Sanger sequencing were carried out to detect potential variants. RESULTS: The patient's main features included micropenis and hypospadia. He was found to harbor compound heterozygous c.680G>A (p.R227Q) and c.3G>T (p.M1I) variants of the SRD5A2 gene. Among these, c.680G>A (p.R227Q) was inherited from his father and was a known pathogenic mutation, while c.3G>T (p.M1I) was inherited from his mother and was unreported previously. CONCLUSION The compound heterozygous variants of the SRD5A2 gene probably underlay the disease in this child, who was eventually diagnosed with 5α-reductase 2 deficiency.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hypospadias ; Male ; Membrane Proteins/genetics* ; Mutation ; Retrospective Studies ; Steroid Metabolism, Inborn Errors ; Steroids

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

PURPOSE: Type III 5-alpha reductase (SRD5A3; steroid 5-alpha reductase 3) may be associated with the progression of prostate cancer (PCa). The aim of our study was to determine whether the length of AC repeats in the SRD5A3 gene is associated with the risk of PCa and the expression of androgen receptor (AR) protein in Korean men. MATERIALS AND METHODS: We compared the length of AC repeats in the short tandem repeat (STR) region of the SRD5A3 gene in 68 PCa patients and 81 control subjects by genotyping. A total of 55 patients in the PCa group underwent radical prostatectomy. We evaluated the expression of AR protein by using Western blotting and tested the association between the type of AC repeats in the SRD5A3 gene and AR protein expression and clinical and pathologic parameters. RESULTS: The short type of STR had less than 21 copies of AC repeats in the SRD5A3 gene. The SS type (short and short type) of STR of the SRD5A3 gene was 2.2 times as likely to occur in PCa patients as in controls (odds ratio, 2.21; 95% confidence interval, 1.14 to 4.31; p=0.019). However, AC repeats of the SRD5A3 gene were not associated with AR protein expression or clinical or pathologic parameters in PCa samples. CONCLUSIONS: These results suggest that the short AC repeats of SRD5A3 polymorphism are associated with an increased risk of PCa. SRD5A3 polymorphism may contribute to a genetic predisposition for PCa.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; Blotting, Western ; Coat Protein Complex I ; Genetic Predisposition to Disease ; Humans ; Microsatellite Repeats ; Oxidoreductases ; Passive Cutaneous Anaphylaxis ; Polymorphism, Genetic ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Receptors, Androgen

OBJECTIVETo analyze the karyotypes and SRD5A2 gene mutations in 25 patients with sporadic or familial hypospadias.

METHODSThe patients included 10 adults and 15 children, whose chromosomes were analyzed by G-banded karyotyping, and the SRD5A2 genes were sequenced.

RESULTSTwo patients were found to have an abnormal karyotype, while eight have carried compound heterozygous mutations of the SRD5A2 gene, which included 5 genotypes formed by 6 types of mutations, i.e., p.G203S/p.R227Q, p.R227Q/p.R246Q, p.Q6X/p.Q71X, p.L20P/p.G203S, and p.Q71X/p.R227Q. Mutations of the SRD5A2 gene were present in 32% (8/25) of all patients, 35% (8/23) in those with a normal karyotype, and 44.4% (8/18) in those with proximal type hypospadia. Bioinformatic analysis, literature review and pedigree analysis confirmed that all such mutations are pathogenic.

CONCLUSIONChromosomal anomalies and mutations of the SRD5A2 gene are the main cause of hypospadias. Sequencing of the SRD5A2 gene may explain the etiology of nearly half of the patients with proximal type of hypospadas but a normal karyotype, which can facilitate genetic consulting.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; genetics ; metabolism ; Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; Female ; Humans ; Hypospadias ; enzymology ; genetics ; Infant ; Infant, Newborn ; Karyotyping ; Male ; Membrane Proteins ; genetics ; metabolism ; Mutation ; Young Adult

AIMTo identify the genotype of two Indians with male pseudohermaphroditism.

METHODSStandard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carried out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5alpha-reductase type 2 gene (SRD5A2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus.

RESULTSWe found an SRD5A2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India.

CONCLUSIONIdentification of the R246Q mutation of the SRD5A2 gene from two unrelated Indian families possibly extends the founder gene effect.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; genetics ; Child ; Dihydrotestosterone ; blood ; Disorders of Sex Development ; genetics ; pathology ; Family Health ; Follicle Stimulating Hormone ; blood ; Founder Effect ; Genitalia, Male ; abnormalities ; Humans ; Hypospadias ; genetics ; pathology ; India ; Luteinizing Hormone ; blood ; Male ; Mutation, Missense ; Testosterone ; blood