This study investigated the therapeutic potential of probiotic bifidobacteria, isolated from Iranian fermented dairy products, in a hyperlipidemic animal model. Bifidobacterium strains were extracted from traditional dairy samples and screened using physiological and phenotypic examinations, 16S rRNA analysis, and probiotic properties such as tolerance to gastrointestinal juice, antimicrobial activity, and antibiotic susceptibility. The ability of the screened bifidobacteria to reduce serum and liver lipids in vivo was tested using male Wistar rats. Six strains of bifidobacteria were isolated from traditional Iranian fermented dairy. These strains showed promising in vitro activity in lowering triglyceride and cholesterol, tolerance to simulated gastrointestinal juice, the ability to adhere to Caco-2 cells, acceptable antibiotic susceptibility, and a broad spectrum of antibacterial activity. The diet supplemented with isolated bifidobacteria significantly reduced serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), liver tissue lipid levels, and hepatic enzymes in animals when compared to a high-fat diet without strains (p < 0.01). Additionally, the potential probiotic-supplemented diet significantly increased bile acid excretion in the feces and upregulated hepatic CYP7A1 expression levels (p < 0.05), while NPC1L1, ACAT2, and MTP gene expressions in small intestinal cells were downregulated (p < 0.05). Bifidobacteria isolated from Iranian traditional dairy showed potential for use in the production of fermented foods that have hypolipemic activity in the host.

• Klíčová slova
• Bifidobacteria, Cholesterol-lowering, Probiotics, Triglyceride-lowering,
• MeSH
• antibakteriální látky farmakologie   MeSH
• Bifidobacterium * genetika   izolace a purifikace   metabolismus   MeSH
• Caco-2 buňky MeSH
• cholesterol-7-alfa-hydroxylasa genetika   metabolismus   MeSH
• cholesterol krev   metabolismus   MeSH
• feces mikrobiologie   MeSH
• hyperlipidemie * MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mléčné výrobky mikrobiologie   MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar * MeSH
• probiotika * aplikace a dávkování   farmakologie   MeSH
• RNA ribozomální 16S genetika   MeSH
• triglyceridy krev   metabolismus   MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Írán MeSH
• Názvy látek
• antibakteriální látky MeSH
• cholesterol-7-alfa-hydroxylasa MeSH
• cholesterol MeSH
• RNA ribozomální 16S MeSH
• triglyceridy MeSH
• žlučové kyseliny a soli MeSH

BACKGROUND 21-hydroxylase deficiency, an essential enzyme for glucocorticoid and mineralocorticoid synthesis, is the cause of congenital adrenal hyperplasia (CAH) in more than 95% of cases. It is an autosomal recessive disorder encoded by the CYP21A2 gene, categorized into classical forms, which encompass the salt-wasting (SW) and simple virilizing (SV) forms, as well as the nonclassical form (NC). The aim of medical treatment is to replace missing glucocorticoids and, if necessary, mineralocorticoids, while also reducing elevated adrenal androgens. CASE REPORT We present the case of a 42-year-old woman with CAH who discontinued therapy during adolescence and was admitted to hospital with fatigue, nausea, and severe abdominal pain. A CT scan showed an extreme enlargement of the adrenal glands. Laboratory tests revealed elevated levels of 17-hydroxyprogesterone and other adrenal androgens, along with normal plasma metanephrine levels. Decreased morning cortisol levels suggested partial adrenal insufficiency requiring glucocorticoid replacement therapy. Due to the development of several serious complications and clinical deterioration, the multidisciplinary team recommended bilateral removal of masses measuring 300×250×200 mm on the right side and 250×200×200 mm on the left side. Histological and immunochemical examination confirmed the presence of giant myelolipomas with adrenal cortex hyperplasia. CONCLUSIONS Adrenal tumors, particularly myelolipomas, have a higher prevalence in patients with CAH. Our case report provides further evidence of the suspected link between non-compliant CAH therapy and the development of myelolipomas, along with promotion of their pronounced growth.

• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• kongenitální adrenální hyperplazie * komplikace   diagnóza   genetika   MeSH
• lidé MeSH
• lipom * MeSH
• myelolipom * diagnóza   chirurgie   komplikace   MeSH
• nadledviny MeSH
• nádory nadledvin * komplikace   diagnóza   MeSH
• steroid-21-hydroxylasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• CYP21A2 protein, human MeSH Prohlížeč
• glukokortikoidy MeSH
• steroid-21-hydroxylasa MeSH

Microbiota plays a role in shaping the HPA-axis response to psychological stressors. To examine the role of microbiota in response to acute immune stressor, we stimulated the adaptive immune system by anti-CD3 antibody injection and investigated the expression of adrenal steroidogenic enzymes and profiling of plasma corticosteroids and their metabolites in specific pathogen-free (SPF) and germ-free (GF) mice. Using UHPLC-MS/MS, we showed that 4 hours after immune challenge the plasma levels of pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone (CORT), 11-dehydroCORT and their 3α/β-, 5α-, and 20α-reduced metabolites were increased in SPF mice, but in their GF counterparts, only CORT was increased. Neither immune stress nor microbiota changed the mRNA and protein levels of enzymes of adrenal steroidogenesis. In contrast, immune stress resulted in downregulated expression of steroidogenic genes (Star, Cyp11a1, Hsd3b1, Hsd3b6) and upregulated expression of genes of the 3α-hydroxysteroid oxidoreductase pathway (Akr1c21, Dhrs9) in the testes of SPF mice. In the liver, immune stress downregulated the expression of genes encoding enzymes with 3β-hydroxysteroid dehydrogenase (HSD) (Hsd3b2, Hsd3b3, Hsd3b4, Hsd3b5), 3α-HSD (Akr1c14), 20α-HSD (Akr1c6, Hsd17b1, Hsd17b2) and 5α-reductase (Srd5a1) activities, except for Dhrs9, which was upregulated. In the colon, microbiota downregulated Cyp11a1 and modulated the response of Hsd11b1 and Hsd11b2 expression to immune stress. These data underline the role of microbiota in shaping the response to immune stressor. Microbiota modulates the stress-induced increase in C21 steroids, including those that are neuroactive that could play a role in alteration of HPA axis response to stress in GF animals.

• Klíčová slova
• anti-CD3, germ-free, gut microbiota, immune stress, mice, steroidogenic genes, steroids,
• MeSH
• enzym štěpící postranní řetězce cholesterolu genetika   metabolismus   MeSH
• kortikosteron metabolismus   MeSH
• mikrobiota * MeSH
• myši MeSH
• steroidy metabolismus   MeSH
• systém hypofýza - nadledviny metabolismus   MeSH
• systém hypotalamus-hypofýza * metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• enzym štěpící postranní řetězce cholesterolu MeSH
• kortikosteron MeSH
• steroidy MeSH

Bone morphogenetic proteins (BMPs) and receptors (BMPR-1A, BMPR-1B, BMPR-2) have been shown to be vital for female reproduction, while their roles in males are poorly described. Our study was undertaken to specify the function of BMPR-1B in steroidogenic enzyme gene expression, testosterone production and reproductive development in male mice, given that Bmpr1b mRNA is expressed in mouse testis and Bmpr1b knockout results in compromised fertility. Male mice were passively immunized for 6 days with anti-BMPR-1B in the presence or absence of exogenous gonadotrophins. We then measured the effects of anti-BMPR-1B on testicular hydroxysteroid dehydrogenase isoforms (Hsd3b1, Hsd3b6, and Hsd17b3) and aromatase (Cyp19) mRNA expression, testicular and serum testosterone levels, and testis and seminal vesicle weight. In vitro testosterone production in response to anti-BMPR-1B was determined using testicular culture, and Leydig cell culture in the presence or absence of gonadotrophins. In Leydig cell culture the contribution of seminiferous tubules and Leydig cells were examined by preconditioning the media with these testicular constituents. In adult mice, anti-BMPR-1B increased testosterone and Hsd3b1 but decreased Hsd3b6 and Cyp19 mRNA. In adult testicular culture and seminiferous tubule conditioned Leydig cell culture, anti-BMPR-1B reduced testosterone, while in normal and Leydig cell conditioned Leydig cell culture it increased testosterone levels. In pubertal mice, anti-BMPR-1B reduced gonadotrophin stimulated seminal vesicle growth. In conclusion, BMPR-1B has specific developmental functions in the autocrine and paracrine regulation of testicular steroidogenic enzyme gene expression and testosterone production in adults and in the development of seminal vesicles during puberty.

• MeSH
• aromatasa metabolismus   MeSH
• exprese genu MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši MeSH
• pohlavní dospělost MeSH
• receptory kostního morfogenetického proteinu metabolismus   MeSH
• testis * metabolismus   MeSH
• testosteron * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aromatasa MeSH
• kostní morfogenetické proteiny MeSH
• messenger RNA MeSH
• receptory kostního morfogenetického proteinu MeSH
• testosteron * MeSH

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.

• MeSH
• adenom kůry nadledvin * MeSH
• adrenokortikální nádory * MeSH
• aldosteron MeSH
• buněčná adhezní molekula 1 MeSH
• cytochrom P450 CYP11B2 MeSH
• hyperaldosteronismus * MeSH
• hypertenze * MeSH
• lidé MeSH
• mezerový spoj MeSH
• mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldosteron MeSH
• buněčná adhezní molekula 1 MeSH
• CADM1 protein, human MeSH Prohlížeč
• cytochrom P450 CYP11B2 MeSH

OBJECTIVE: To analyze the mutational spectrum, clinical characteristics, genotype-phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia. DESIGN AND METHODS: Data were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations. To detect deletions, conversions, point mutations, or other sequence changes in the CYP21A2 gene, high-resolution genotyping was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C). RESULTS: 64% of the individuals had the salt-wasting form (SW-CAH), 15% the simple virilizing form (SV-CAH), and 21% the non-classic (NC-CAH). CYP21A2 gene deletion/conversion and c.293-13A/C>G pathogenic variant accounted together for 55.5% of the affected alleles. In SV-CAH p.Ile172Asn was the most common pathogenic variant (28.13%), while in NC-CAH p.Val282Leu (33.33%), CYP21A2 gene deletion/conversion (21.43%), c.293-13A/C>G (14.29%), Pro30Leu (11.90%). The frequency of alleles with multiple pathogenic variants was higher in Slovenian patients (15.83% of all alleles). Severe genotypes (0 and A) correlated well with the expected phenotype (SW in 94.74% and 97.3%), while less severe genotypes (B and C) correlated weaklier (SV in 50% and NC in 70.8%). The median age of SW-CAH patients at the time of diagnosis was 6 days in Slovakia vs. 28.5 days in Slovenia (p=0.01). Most of the Slovak patients in the cohort were detected by NBS. (24 out of 29). TARTs were identified in 7 out of 24 male patients, of whom all (100%) had SW-CAH and all had poor hormonal control. The median age at the diagnosis of TARTs was 13 years. CONCLUSION: The study confirmed the importance of neonatal screening, especially in the speed of diagnosis of severe forms of CAH. The prediction of the 21-OH deficiency phenotype was reasonably good in the case of severe pathogenic variants, but less reliable in the case of milder pathogenic variants, which is consistent compared to data from other populations. Screening for TARTs should be realized in all male patients with CAH, since there is possible remission when identified early.

• Klíčová slova
• 21 hydroxylase deficiency, 21-OH deficiency, CAH, CYP21A2, congenital adrenal hyperplasia, genotype-phenotype, newborn screening, testicular adrenal rest tumors (TART),
• MeSH
• kongenitální adrenální hyperplazie * epidemiologie   genetika   diagnóza   MeSH
• lidé MeSH
• nádor ze zbytků nadledviny * epidemiologie   genetika   MeSH
• steroid-21-hydroxylasa genetika   MeSH
• testikulární nádory * epidemiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH
• Názvy látek
• CYP21A2 protein, human MeSH Prohlížeč
• steroid-21-hydroxylasa MeSH

In the present study, we investigated the effect of acrylamide (ACR) exposure during pregnancy on the ovary of female adult offspring of two subsequent generations. Sixty-day-old Wistar albino female rats were given different doses of ACR (2.5 and 10 mg/kg/day) from day 6 of pregnancy until giving birth. Females from the first generation (AF1) were fed ad libitum, and thereafter, a subgroup was euthanized at 8 weeks of age and ovary samples were obtained. The remaining females were maintained until they reached sexual maturity (50 days old) and then treated in the same way as the previous generation to obtain the second generation of females (AF2). The histopathological examination indicated a high frequency of corpora lutea along with an increased number of antral follicles that reached the selectable stage mainly at a dose of 2.5 mg/kg/day. Interestingly, ACR exposure significantly increased the mRNA levels of CYP19 gene and its corresponding CYP19 protein expression in AF1 females. The TUNEL assay showed a significantly high rate of apoptosis in stromal cells except for dose of 2.5 mg/kg/day. However, in AF2 females, ACR exposure significantly increased the number of degenerating follicles and cysts while the number of growing follicles was reduced. Moreover, in both ACR-treated groups, estradiol-producing enzyme CYP19A gene and its corresponding protein were significantly reduced, and an excessive apoptosis was produced. We concluded that the ovarian condition of AF1 females had considerable similarity to the typical early perimenopausal stage, whereas that of AF2 females was similar to the late perimenopausal stage in women.

• MeSH
• akrylamid toxicita   MeSH
• apoptóza MeSH
• aromatasa * genetika   MeSH
• furylfuramid MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• poměr pohlaví MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamid MeSH
• aromatasa * MeSH
• furylfuramid MeSH

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used. The biological activity of the obtained compounds was studied in a number of tests, including their effects on 17α-hydroxylase and 17,20-lyase activity of human CYP17A1 and the ability of selected compounds to affect the downstream androgen receptor signaling. Three derivatives diminished the transcriptional activity of androgen receptor and displayed reasonable antiproliferative activity. The candidate compound, 24j (17R)-17-((3-(2-hydroxypropan-2-yl)isoxazol-5-yl)methyl)-androst-5-en-3β-ol, suppressed the androgen receptor signaling and decreased its protein level in two prostate cancer cell lines, LNCaP and LAPC-4. Interaction of compounds with CYP17A1 and the androgen receptor was confirmed and described by molecular docking.

• Klíčová slova
• CYP17A1, LAPC-4, LNCaP, Weinreb amide, androgen receptor, androgen signaling, isoxazoles, molecular docking, prostate cancer,
• MeSH
• androgenní receptory metabolismus   MeSH
• antitumorózní látky * chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty * farmakoterapie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• steroid-17-alfa-hydroxylasa metabolismus   MeSH
• steroidy farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgenní receptory MeSH
• antitumorózní látky * MeSH
• steroid-17-alfa-hydroxylasa MeSH
• steroidy MeSH

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

• Klíčová slova
• gas chromatography-tandem mass spectrometry, gestational age, gestational diabetes mellitus, immunoprotective steroids, maternal blood, mixed cord blood, neuroactive steroids, steroidome,
• MeSH
• 20-hydroxysteroid dehydrogenasy metabolismus   MeSH
• chromatografie plynová MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• druhý trimestr těhotenství metabolismus   MeSH
• gestační diabetes metabolismus   MeSH
• lidé MeSH
• metabolomika metody   MeSH
• oxidoreduktasy metabolismus   MeSH
• steroid-17-alfa-hydroxylasa metabolismus   MeSH
• steroidy analýza   MeSH
• tandemová hmotnostní spektrometrie MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 20-hydroxysteroid dehydrogenasy MeSH
• 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase MeSH Prohlížeč
• 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Prohlížeč
• CYP17A1 protein, human MeSH Prohlížeč
• CYP3A7 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• oxidoreduktasy MeSH
• steroid-17-alfa-hydroxylasa MeSH
• steroidy MeSH

Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid production and metabolism, expressing a vast range of steroidogenic enzymes. Nevertheless, a comprehensive characterization of steroidogenic pathways in the human placenta and potential developmental changes occurring during gestation are poorly understood. Furthermore, the specific contribution of trophoblast cells in steroid release is largely unknown. Thus, this study aimed to (i) identify gestational age-dependent changes in the gene expression of key steroidogenic enzymes and (ii) explore the role of trophoblast cells in steroid biosynthesis and metabolism. Quantitative and Droplet Digital PCR analysis of 12 selected enzymes was carried out in the first trimester (n = 13) and term (n = 20) human placentas. Primary trophoblast cells (n = 5) isolated from human term placentas and choriocarcinoma-derived cell lines (BeWo, BeWo b30 clone, and JEG-3) were further screened for gene expression of enzymes involved in placental synthesis/metabolism of steroids. Finally, de novo steroid synthesis by primary human trophoblasts was evaluated, highlighting the functional activity of steroidogenic enzymes in these cells. Collectively, we provide insights into the expression patterns of steroidogenic enzymes as a function of gestational age and delineate the cellular origin of steroidogenesis in the human placenta.

• Klíčová slova
• gestation, placenta, steroid metabolism, steroidogenesis, trophoblast,
• MeSH
• choriokarcinom metabolismus   patologie   MeSH
• dospělí MeSH
• gestační stáří MeSH
• kultivované buňky MeSH
• lidé MeSH
• novorozenec MeSH
• placenta cytologie   metabolismus   MeSH
• první trimestr těhotenství metabolismus   MeSH
• regulace genové exprese * MeSH
• steroidhydroxylasy genetika   metabolismus   MeSH
• steroidy metabolismus   MeSH
• těhotenství MeSH
• trofoblasty cytologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• steroidhydroxylasy MeSH
• steroidy MeSH