HSD11B2 Gene Research Articles

How inversion variants can shape neural circuitry: Insights from the three-morph mating tactics of ruffs.

Behavior polymorphisms underlying alternative mating tactics can evolve due to genetic inversions, especially when inversions capture sets of genes involved in hormonal regulation. In the three-morph system of the ruff (Calidris pugnax), two alternative morphs (Satellites and Faeders) with distinct behaviors and low circulating testosterone are genetically determined by an inverted region on an autosomal chromosome. Here, we discuss recent findings on the ruff and present novel insights into how an inversion that poses drastic constraints on testosterone production might lead to morph-specific differences in brain areas that regulate social behavior. A gene responsible for converting testosterone to androstenedione (HSD17B2) is located inside the inverted region and is a promising candidate. We identify a single missense mutation in the HSD17B2 gene of inverted alleles that is responsible for a 350-500% increase in testosterone to androstenedione conversion, when mutated in the human HSD17B2 protein. We discuss new evidence of morph differences in neural HSD17B2 expression in embryos and circulating androgens in sexually-immature juveniles. We suggest processes that shape morph differences in behavior likely begin early in ontogeny. We propose that the organization of behaviorally relevant neuron cell types that are canonically sexually dimorphic, such as subpopulations of aromatase and vasotocin neurons, should be particularly affected due to the life-long condition of low circulating testosterone in inversion morphs. We further emphasize how HSD17B2 catalytic activity extends beyond androgens, and includes estradiol oxidation into estrone and progesterone synthesis. Lastly, we underscore dimerization of HSD17B2 as an additional layer of complexity that merits consideration.

The protective effect of L-carnitine on testosterone synthesis pathway, and spermatogenesis in monosodium glutamate-induced rats

BackgroundMonosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats.MethodsSixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed.ResultsL-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p < 0.05). Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group.ConclusionThe study’s findings demonstrated that L-carnitine due to its anti-oxidant properties, ameliorated the reproductive abnormalities in the male rats exposed to MSG.

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency.

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3βHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients’ age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also—mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing’ syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison’s disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem–mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as “novel pathogenic mutation” (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3βHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

Novel Genomic Variants, Atypical Phenotypes and Evidence of a Digenic/Oligogenic Contribution to Disorders/Differences of Sex Development in a Large North African Cohort.

In a majority of individuals with disorders/differences of sex development (DSD) a genetic etiology is often elusive. However, new genes causing DSD are routinely reported and using the unbiased genomic approaches, such as whole exome sequencing (WES) should result in an increased diagnostic yield. Here, we performed WES on a large cohort of 125 individuals all of Algerian origin, who presented with a wide range of DSD phenotypes. The study excluded individuals with congenital adrenal hypoplasia (CAH) or chromosomal DSD. Parental consanguinity was reported in 36% of individuals. The genetic etiology was established in 49.6% (62/125) individuals of the total cohort, which includes 42.2% (35/83) of 46, XY non-syndromic DSD and 69.2% (27/39) of 46, XY syndromic DSD. No pathogenic variants were identified in the 46, XX DSD cases (0/3). Variants in the AR, HSD17B3, NR5A1 and SRD5A2 genes were the most common causes of DSD. Other variants were identified in genes associated with congenital hypogonadotropic hypogonadism (CHH), including the CHD7 and PROKR2. Previously unreported pathogenic/likely pathogenic variants (n = 30) involving 25 different genes were identified in 22.4% of the cohort. Remarkably 11.5% of the 46, XY DSD group carried variants classified as pathogenic/likely pathogenic variant in more than one gene known to cause DSD. The data indicates that variants in PLXNA3, a candidate CHH gene, is unlikely to be involved in CHH. The data also suggest that NR2F2 variants may cause 46, XY DSD.

Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes.

A mouse testis-specific long noncoding RNA (lncRNA), Start, is localized in the cytosol of Leydig cells and in the nucleus of pachytene spermatocytes. We previously showed that Start regulates steroidogenesis through controlling the expression of Star and Hsd3b1 genes in Leydig cells, but its function in germ cells was not known. Here we verified that a spermatocyte-specific protease gene, Prss43/Tessp-3, was downregulated in Start-knockout testes. To investigate the transcriptional regulatory activity of Start in spermatocytes, we first performed a series of reporter gene assays using a thymidine kinase promoter in spermatocyte-derived GC-2spd(ts) cells. A 5.4-kb genome sequence encompassing Start exhibited enhancer activity for this promoter, and the activity was decreased by knockdown of Start. Deletion of the Start promoter and replacement of the Start sequence abolished the enhancer activity and, consistently, the activity was detected in further experiments only when Start was actively transcribed. We then examined whether the Prss43/Tessp-3 gene could be a target of Start. A reporter gene assay demonstrated that the 5.4-kb sequence exhibited enhancer activity for a Prss43/Tessp-3 promoter in GC-2spd(ts) cells and that the activity was significantly decreased by knockdown of Start. These results suggest that Start functions in transcriptional activation of the Prss43/Tessp-3 gene in spermatocytes. Given that Start is presumed to regulate steroidogenic genes at the posttranscriptional level in Leydig cells, the function in spermatocytes is a novel role of Start. These findings provide an insight into multifunctionality of lncRNAs in the testis.

Expression of HSD3B1 and HSD3B2 Genes in Adenocarcinoma and Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa) are 2 prostatic lesions affecting most men over 60 years old. It was shown that there is a significant relationship between BPH and PCa. BPH could lead to escalating risks of PCa. Functional androgen signaling is involved in the maintenance and development of the normal prostate. Defects in this signaling pathway are also involved in the development of prostate cancer and BPH. Due to the importance of the HSD3B gene family in steroid hormone biosynthesis, it plays an important role in hormone-dependent tumors such as prostate cancer. Objectives: In this study, we evaluated the expression of HSD3B1 and HSD3B2 genes in BPH and PCa by real-time polymerase chain reaction (PCR). Methods: A total of 40 BPH and 40 PCa samples were evaluated. After RNA extraction and complementary DNA (cDNA) synthesis, real-time PCR was performed with specific primers, and the results were compared with age, pathology stage, Gleason score, and prostate-specific antigen (PSA) range parameters. Results: The results showed that both genes were downregulated in PCa compared to BPH. This reduction was more noticeable in the HSD3B1 gene than in the HSD3B2 gene, but it was not statistically significant. No significant relationship was observed between age, disease stage, Gleason score, and PSA level with changes in the expression of these 2 genes in the 2 groups. Conclusions: Increased expression of these 2 genes does not play a significant role in PCa but can play a role in the development of BPH.

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2.

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland.Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test.Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension.Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

3-β-hydroxysteroid dehydrogenase 1 (HSD3B1) is shown to affect dihydrotestosterone level in prostatic tissue which is a risk factor for prostate cancer (PC). The present study aimed to determine whether rs33937873 (G313A) and rs6203 (C338T) single nucleotide polymorphisms (SNP) in HSD3B1 gene was a potential risk factor for PC susceptibility and can predict the recurrence of PC in Egyptian patients. A total of 186 Egyptian patients were selected with incident primary PC and compared with 180 age healthy controls. The frequencies and the main effect of rs33937873 and rs6203 in HSD3B1 were compared and investigated between the patients and control using genotyping technique and statistical analysis. The mutant GA genotype of G313A in rs33937873 SNP was considered as an independent risk for PC in the multivariate regression analysis [odds ratio (OR)=2.7, 95% confidence intervals (CI): 1.2-5.5, P=0.01] together with positive history of hypertension (HTN) (OR=6.2, 95% CI: 3.2-12.1, P=0.0001) and begin prostatic hyperplasia (BPH; OR=8.9, 95% CI: 4.5-17.5, P=0.0001). Conversely, in rs6203 (C338T), C allele is considered as major risk allele in the development of PC (OR=1.8, 95% CI: 1.3-2.4, P=0.0003). The univariate logistic regression analyses indicated that CC genotype of rs6203 was a PC risk factor (OR=1.9, 95% CI: 1.3-2.9, P=0.002). In addition, the frequency of the A-C haplotype established by rs33937873-rs6203 was also significantly higher for PC (P=0.013). The predication of PC recurrence was associated only with positive family history (OR=7.7, 95% CI: 2.3-25.9, P=0.001) and not for The G313A and C338T SNPs. These results suggested that the two HSD3B1 polymorphisms rs33937873 and rs6203 may modify the risk of PC, particularly among patients with HTN and history of BPH, suggesting them as prominent future markers for prediction of PC risk.

Polymorphism of 3β-Hydroxysteroid Dehydrogenase-1 in patients with prostate cancer in middle Euphrates of Iraq

Androgens play critical roles in prostate carcinogenesis as well as prostate cancer progression. Androgen-deprivation therapy (ADT), which reduces testosterone production and inhibits androgen action in prostate cancer cells, has been the criterion standard therapy for metastatic prostate cancer (1). Although initially most prostate cancers respond well to ADT, most patients eventually progress to castration-resistant prostate cancer (CRPC), which is mainly thought to be because androgen receptor reactivation is induced by several mechanisms. One of those mechanisms have been identified to be intratumoral androgen synthesis mostly from adrenal precursor steroids and at least in part due to de novo synthesis from cholesterol which is supported by increased expression of several genes encoding steroidogenic enzymes including HSD3B, HSD17B, and SRD5A in CRPC. Among them, HSD3B1 gene encodes 3β-hydroxysteroid dehydrogenase-1, which is mainly expressed in peripheral tissues including the prostate (another isoform, 3β-hydroxysteroid dehydrogenase-2 was mainly expressed in adrenal gland and gonad in human) and is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis. Genetic polymorphism in HSD3B1 encoding 3β-hydroxysteroid dehydrogenase-1 has been shown to be associated with oncological outcome for prostate cancer. This study to investigate the significance of missense polymorphism in HSD3B1 gene (rs1047303) among men with prostate cancer.

P-300 Evaluation of CYP19A1 gene expression in luteinized granulosa cells of women affected by endometriosis undergoing assisted reproductive technology (ART) treatments

Abstract Study question Does endometriosis affect the expression of the aromatase gene CYP19A1 in the cumulus oophorous (COCs) and mural lutein-granulosa cells (GCs) influencing ART procedures? Summary answer Endometriosis does not impair CYP19A1 gene expression. However, the correlation between the aromatase expression and the number of oocytes retrieved is lost in endometriosis patients. What is known already Endometriosis-related infertility could be associated with a dysregulation of oocytes development. Indeed, endometriosis seems to have a negative effect on the intrafollicular environment, hindering oocyte maturation. A dysregulated synthesis of steroid hormones by GCs in the ovaries of affected women may be at the basis of an inadequate folliculogenesis. In line, some studies have investigated the expression levels of aromatase p450 ( CYP19A1 ) -the key enzyme involved in 17β-estradiol (E2) synthesis - in GCs and COCs collected from endometriosis women, reporting controversial results. Study design, size, duration In order to identify novel prognostic factors of ART outcomes in affected women, we set the evaluation of CYP19A1 expression in GCs samples isolated from endometriosis patients undergoing ART in comparison to control women. In a subgroup of patients, COCs were also collected. CYP19A1, StAR and 3βHSD gene expression was evaluated in both cell types. Finally, we evaluated the association between the expression of the analyzed genes and E2 levels with the clinical ART outcomes Participants/materials, setting, methods GCs were isolated from follicular fluids(FF) of n = 68 women with stage III-IV endometriosis and of n = 69 control patients. CYP19A1 gene expression was quantified by qPCR. 17β-estradiol levels in FF were assessed using an ELISA kit. In addition to CYP19A1 gene expression, mRNA levels of StAR and 3βHSD both in GCs and COCs (n = 20 endometriosis;n=21 controls) were evaluated in both cell types using qPCR. Differences between the two patients’ groups were estimated using linear regression models. Main results and the role of chance qPCR results showed no differences in mRNA expression of CYP19A1, StAR and 3βHSD in both GCs and COCs between the two groups of ART patients. These results were supported by the presence of the same concentration of E2 in the FF of controls (median: 877.7 ng/mL) and endometriosis patients (median: 878.3 ng/mL) (p-value=0.87). Linear regression model including as input variables gene expression values and ART outcomes showed that the blastulation rate was the only ART outcome associated with the expression levels of CYP19A1 (p-value=0.043, 95% CI: 0.001-0.061). In particular, a decrease of aromatase levels was associated with an increase in blastulation rate. After stratification of the population based on the presence of the disease, it emerged that, in the control group, the CYP19A1 expression correlated with the number of oocytes retrieved [β:-1.214;95%CI: -2.085 - (-0.343); p-value=0.007], while in the group of patients with endometriosis this association was no more present [β:-0.003;95%CI:-0.468 - 0.461; p-value=0.988)]. These results do not support data from the literature indicating that aromatase expression is reduced in GCs of affected women, but they highlight a potential disease-related mechanism affecting the ovulation process in these women Limitations, reasons for caution These findings need to be validated in a different cohort of samples. An RNA-seq approach is needed in order to validate our results and to obtain the overall transcriptome profiles of GCs and COCs in endometriosis patients. Wider implications of the findings Our data do not confirm previous evidence supporting a reduced expression/activity of aromatase in GCs in endometriosis. However, they suggest that aromatase may have a complex and sophisticated regulation of its expression in this cell type, which is not maintained in presence of endometriosis. Trial registration number not applicable

Effects of sugar cane extract on steroidogenesis in testicular interstitial cells of male Japanese quail (Coturnix japonica)

Sugar cane extract (SCE) is the end product of glucose, fructose, and sucrose elimination in molasses. SCE has various biological effects, such as anti-inflammation and antioxidation, and it is commonly found in animal feed. The present research is aimed at investigating the reproductive endocrine influence of SCE in male Japanese quails (Coturnix japonica) by feeding SCE containing food. In addition, in vitro Leydig cell culture was conducted to clarify the mechanism of SCE's influence. Our results showed that SCE feed extended the latency to the first neck grab, decreased male quail testis and epididymis weights, cloaca gland size, and reduced serum testosterone concentrations. Steroidogenic enzymes 3βHSD, 17βHSD, P450c17, and P450scc gene expression in the testis were decreased in the SCE groups. Western blot analysis showed decreased 3βHSD in the testis after feeding SCE. Isolated testicular interstitial cells cultured with SCE and ovine-LH suppressed testosterone secretion and 3βHSD gene expression. In conclusion, SCE as a feed additive has an impact on the sexual behavior and reproductive function of male Japanese quail, with the suppression of steroidogenesis in the Leydig cell. Our results may provide beneficial information to the livestock management and the poultry industry.

So, and if it is not congenital adrenal hyperplasia? Addressing an undiagnosed case of genital ambiguity

BackgroundThe Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene. In this disorder/difference of sex development, the conversion of androstenedione into testosterone is impaired. The appearance of external genitalia of 46,XY individuals varies from typically male to almost female.Case presentationWe report on a child presenting severe ambiguous genitalia. Due to access constraints, specialized care did not start until the child was 10 months old. Parents are consanguineous and were born in an area of high isonymy that is a cluster for rare recessive diseases. A new homozygous missense variant c.785G > T was found in exon 10 of the HSD17B3 gene.ConclusionsResearchers-clinicians and researchers-researchers collaborative efforts to elucidate the genetic basis of this disease were critical since this etiologic investigation is not available through the public health system. This case exemplifies the families’ pilgrimage in cases of genital ambiguity due to a rare genetic condition. Recognizing the etiology was the baseline to provide information on prognosis and treatment options, and to shelter family and child doubts and hopes in order to better support their decisions.

11β-HSD1 Inhibitor Alleviates Non-Alcoholic Fatty Liver Disease by Activating the AMPK/SIRT1 Signaling Pathway.

We investigated the effect of an 11β-HSD1 inhibitor (H8) on hepatic steatosis and its mechanism of action. Although H8, a curcumin derivative, has been shown to alleviate insulin resistance, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Rats were fed a high-fat diet (HFD) for 8 weeks, intraperitoneally injected with streptozotocin (STZ) to induce NAFLD, and, then, treated with H8 (3 or 6 mg/kg/day) or curcumin (6 mg/kg/day) for 4 weeks, to evaluate the effects of H8 on NAFLD. H8 significantly alleviated HFD+STZ-induced lipid accumulation, fibrosis, and inflammation as well as improved liver function. Moreover, 11β-HSD1 overexpression was established by transfecting animals and HepG2 cells with lentivirus, carrying the 11β-HSD1 gene, to confirm that H8 improved NAFLD, by reducing 11β-HSD1. An AMP-activated protein kinase (AMPK) inhibitor (Compound C, 10 μM for 2 h) was used to confirm that H8 increased AMPK, by inhibiting 11β-HSD1, thereby restoring lipid metabolic homeostasis. A silencing-related enzyme 1 (SIRT1) inhibitor (EX572, 10 μM for 4 h) and a SIRT1 activator (SRT1720, 1 μM for 4 h) were used to confirm that H8 exerted anti-inflammatory effects, by elevating SIRT1 expression. Our findings demonstrate that H8 alleviates hepatic steatosis, by inhibiting 11β-HSD1, which activates the AMPK/SIRT1 signaling pathway.

053 Totally extraperitoneal approach (TEP) for gonadectomy for differences in sex development (DSD): Report of 2 cases

Introduction: 17-β-hydroxysteroid dehydrogenase type-3 deficiency (17βHSD-3) is a rare cause of 46XY DSD. Gonadectomy is often offered to prevent further virilization and to continue living in a female gender role [ [1] Chuang J. Vallerie A. Breech L. Saal H.M. Alam S. Crawford P. Rutter M.M. Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?. Int J Pediatr Endocrinol. 2013; 12: 15 Crossref Google Scholar ]. Both laparotomic and laparoscopic approaches to gonadectomy had been described for DSDs [ [2] Dellaportas D. Chatzipapas I. Pandraklakis A. Michala L. Laparoscopic bilateral gonadectomy and inguinal hernia repair with mesh for complete androgen insensitivity syndrome: A case report. J Pediatr Adolesc Gynecol. 2019; 32 (Epub 2019 Feb 27): 443-445 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ]. Retrieval and removal of testes located in the inguinal canal can be technically challenging and requires collaboration with surgical colleagues. Cases: We present 2 cases of DSD with 17βHSD-3. One of them is 16 years old, while the other one is 20 years old. Both cases presented with amenorrhea and clitoral enlargement, whereas the second case also had deepening of voice. Blood tests for both revealed elevated testosterone and androstenedione. MRI findings were similar showing bilateral gonads located in the inguinal canals. Genetic tests revealed 46 XY karyotype and HSD17B3 gene mutation. Both subjects opted to continue with a female gender role and opted for gonadectomy to prevent further virilization. Gonadectomy was performed with a totally extraperitoneal laparoscopic approach. An infraumbilical incision was made and care was taken to enter the potential space above the rectus sheath. Then a balloon was placed via the port to distend the extraperitoneal space and then the laparoscope was inserted. Secondary ports at the suprapubic region and the left lower quadrant were placed. The gonads were mobilized and gonadectomy performed. Gonadectomy was successfully performed for the first case, but for the second case, there was failure to mobilize the gonad and operation was completed with inguinal incisions. Conclusion: Totally extraperitoneal laparoscopic approach for hernia repair is a well-established technique familiar to surgeons [ [3] McKernan J.B. Laws H.L. Laparoscopic repair of inguinal hernias using a totally extraperitoneal prosthetic approach. Surg Endosc. 1993; 7: 26-28 Crossref PubMed Scopus (264) Google Scholar ]. This was the first time the TEP approach has been described for gonadectomy for DSD. By cooperating with surgeons who has abundant experience in operating in this region, one can allow utilization of techniques which were already commonly used. It raises the importance as gynecologists, we should be mindful of technological advances in other specialties as with other aspects of DSD, collaboration with other specialties may lead to advances in patient management.

Effects and related mechanisms of Huang's SiYu pills on Leydig cell function in kidney-yin deficiency rat models

The prescription “Huang's SiYu Pill” (HSYP) was founded by professor Huang Haibo, a famous traditional Chinese medicine in Inner Mongolia, based on long-term clinical experience. In this study we observed the effects of HYSP on sperm quality, hormone level and the expression level of reproductive related genes and proteins in testicular stromal cells of rats with kidney-yin deficiency to explore the therapeutic mechanism of HSYP in the treatment of infertility with kidney-yin deficiency, Liuwei Dihuang Pill group (LDP) and Tamoxifen Citrate Tablets combined with Pancreatic Kallidinogenase Enteric Coated Tablets were used to be the positive control drug. After 25 days of medicine administration, the animals were anesthetized and killed, the serum and testicular tissues were retained for further experiments. The ELISA results showed that HSYP had a better effect on increasing serum FSH level than the conventional Chinese medicine or western medicine, while there was no remarkable difference in the regulation of serum LH in each administration group. The results of RT-qPCR showed that the transcription levels of Cyp11a1, Hsd3b1, Lhcgr and Star genes in the medium and high dose groups of HSYP were significantly upregulated compared with the model group of kidney-yin deficiency, while the expression of Nr5a1 gene was not significantly affected. The results of HE and immunohistochemistry showed that HSYP significantly improved the development level of testicular stromal cells and promoted the expression levels of CYP11A1 and HSD11B1 in testicular stromal cells, compared with the model group of kidney-yin deficiency. Together, our results showed that Huang's SiYu Pills can significantly improve the development and function of Leydig cells in SD rats with kidney-yin deficiency model, which provided a good research basis for deep research on relevant pharmacological mechanisms of the medicine.

Clinical and HSD11B2 gene analysis of a patient with apparent mineralocorticoid excess

患儿 女，12岁，因“发现血压高、血钾低11年，血压控制不佳1个月”就诊于北京儿童医院内分泌遗传代谢科。经过体格检查、血液电解质、血气分析、醛固酮检测、影像学检查、基因检测等手段，确诊为表观盐皮质增多综合征。表观盐皮质增多综合征是一种罕见的单基因原发性高血压，诊断相对困难。及早基因检测有助于早期诊断和规范治疗方可避免靶器官损伤。.

Infantile Neurodegeneration results from Mutants of 17β‐Hydroxysteroid Dehydrogenase Type 10 rather than Aβ‐Binding Alcohol Dehydrogenase

Type 10 17β‐hydroxysteroid dehydrogenase (17β‐HSD10), a mitochondrial homo‐tetrameric multifunctional protein encoded by the HSD17B10 gene is necessary for brain cognitive function. Missense mutations on this gene resulted in HSD10 mitochondrial disease, an inborn error in isoleucine metabolism. A 5‐methylcytosine hotspot in this gene underlying a 388C ̵T transition leads to the HSD10(p.R130C) mutant responsible for about half cases of infantile neurodegeneration. Less females suffers with this disease and usually has milder clinical manifestation due to the X‐inactivation. The binding capability of this dehydrogenase to Aβ‐peptide may play a role in senile neurodegeneration, namely Alzheimer disease, but it appears unrelated to infantile neurodegeneration. Unfortunately, this research field has been interfered by reports of the Aβ‐peptide binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum‐associated Aβ binding protein (ERAB). Both reflect some dubious features of 17β‐HSD10. It is clarified here that ERAB is merely a subunit of 17β‐HSD10, having a fictitious association with the endoplasmic reticulum. 17β‐HSD10 exhibits L‐3‐hydroxyacyl‐CoA dehydrogenase activity so also known as short chain 3‐hydorxyacyl‐CoA dehydrogenase (SCHAD), but it is not involved in the ketone body metabolism as reported for ABAD’s function in the cellular response to nutritional stress. Furthermore, the reported generalized alcohol dehydrogenase data underlying the ABAD activity could not be based upon valid reproducible experiments, and the rediscovery of its mitochondrial localization was preceded by unreferenced 17β‐HSD10 research. Clarification of unreliable ABAD/ERAB data may invigorate this research field, and open new approaches to the understanding and treatment of the HSD17B10gene related disorders including infantile neurodegeneration and Alzheimer’s disease.

Housing Conditions and a Challenge with Lipopolysaccharide on the Day of Estrus Can Influence Gene Expression of the Corpus Luteum in Gilts.

The corpus luteum (CL) is a temporary endocrine gland that plays a decisive role in the reproductive physiology of gilts. Recently, it has been suggested that exogenous factors may compromise the normal functioning of the CL. In the present study, we aimed to understand to what extent an acute and systemic challenge with lipopolysaccharide (LPS) on the day of estrus could compromise gene expression of gilts’ CLs housed in different welfare conditions. For this, we housed 42 gilts in three different housing systems: crates, indoor group pens, and outdoor housing. Then, we challenged six females from each group with LPS and eight with saline (SAL) on the day of estrus. After slaughtering the gilts on the fifth day after the challenge, ovaries were collected for gene expression analysis by RT-qPCR. Housing system and LPS challenge did not have a significant interaction for any genes evaluated; thus, their effects were studied separately. We identified significant (p < 0.05) downregulation of the angiogenic genes VEGF and FTL1 among LPS-challenged animals. Meanwhile, we also observed upregulation of HSD3B1 gene among LPS-challenged animals. We found that STAR and LHCGR genes were differentially expressed depending on the housing system, which indicates that the environment may affect adaptation capabilities. Our results indicate that an acute health challenge on the estrus day alters CL gene expression; however, the role of the housing system remains uncertain.

Spirulina therapeutic potentiality in polycystic ovarian syndrome management using DHEA-induced rat model.

OBJECTIVE: The most prevalent endocrinopathy in women is polycystic ovarian syndrome (PCOS). Multiple gene abnormalities like Ar, Cyp19a1, Hsd3b1, Srd5a1, Bcl-2, and Bax genes are associated with PCOS. Herein, the PCOS model was induced by oral administration of dehydroepiandrosterone (DHEA). Metformin (Met) is one of the most common drugs affecting the most relevant genes involved in PCOS development but with unwanted side effects. Natural treatments have been known for their safer effects. Spirulina (SP) is a type of blue-green algae that contains nutrients and compounds that would treat PCOS and lower the possible side effects of Met in combination therapy. We aim to evaluate the clinical effectiveness and safety of SP on PCOS by multi confirmatory tests and to demonstrate its effects on regulating the expression of multiple genes that are responsible for the occurrence of PCOS in comparison to Met. MATERIALS AND METHODS: Herein, sixty adult female Wistar albino rats were subdivided into equal six groups with 10 rats in each group. All drugs were given orally once daily for one month. The expression of Ar, Cyp19a1, Hsd3b1, Srd5a1, Bcl-2, and Bax genes, were examined by quantitative real-time PCR (qRT-PCR). RESULTS: The present study showed that SP has a remarkable effect on the reduction of the development of PCOS by regulating the expression of the examined genes. As a result, it may be a useful therapy alternative for PCOS complications, symptoms, and infertility as well. CONCLUSIONS: Collectively, SP is considered a promising therapeutic drug in the treatment of PCOS-like symptoms induced by DHEA.

Syndromes of Pseudo-Hyperaldosteronism.

Syndromes of Pseudo-Hyperaldosteronism.