In December of 2019, several cases of unknown atypical respiratory diseases emerged in Wuhan, Hubei Province in China. After preliminary research, it was stated that the disease is transmittable between humans and was named COVID-19. Over the course of next months, it spread all over the world by air and sea transport and caused a global pandemic which affects life of everyone now-a-days. A large number of countries, have since been forced to take precautions such as curfews, lockdowns, wearing facemasks etc. Even with vaccines being produced in mass numbers, lack of targeted therapy continues to be a major problem. According to studies so far it seems that elderly people are more vulnerable to severe symptoms while children tend to by asymptomatic or have milder form the disease. In our review, we focused on gathering data about the virus itself, its characteristics, paths of transmission, and its effect on hormone production and secretion. In such, there is insufficient information in the literature worldwide, especially the ones that focus on the effect of COVID-19 on individual organs systems within the human body. Hence, the present evidence-based study focused on the possible effects of COVID-19 on adrenal gland and gonads i.e. on the process of steroidogenesis and fertility.
- MeSH
- COVID-19 metabolismus patofyziologie virologie MeSH
- fertilita * MeSH
- gonády metabolismus patofyziologie virologie MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- nadledviny metabolismus patofyziologie virologie MeSH
- SARS-CoV-2 patogenita MeSH
- steroidy biosyntéza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Through their receptors at each level of hypothalamo-pituitary-gonadal axis glucocorticoid excess, either endogenous or administered or stress-induced, could affect steroid production in the testis and thus male fertility. The main ways by which glucocorticoids act are as follows: 1) Affecting gonadoliberin and LH synthesis and release through glucocorticoid receptors in hypothalamic neurons and pituitary gonadotropes. 2) By so far not clearly evidenced reduction of the number of LH receptors on the membrane of Leydig cells. 3) By affecting expression and function of steroidogenic enzymes in the testis. 4) By regulation of in situ access of glucocorticoid to its target cells in the testis. 5) By promotion Leydig cell apoptosis. The review provides a survey of physiological and molecular mechanisms staying behind these effects. It does not deal with the clinical effects of glucocorticoid treatment which would substantially exceed the scope of the pater.
- MeSH
- glukokortikoidy farmakologie MeSH
- lidé MeSH
- steroidy biosyntéza MeSH
- testis účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ovarian follicle steroidogenesis associated with embryo quality results in a successful pregnancy. Each follicle consists of an oocyte surrounded by granulosa cells, which secrete several steroid and peptide hormones. Follicles harvested from women who conceived after assisted reproductive therapy (ART) had significantly higher estradiol levels in follicular fluids than the follicles from women who failed to conceive after ART. The higher follicular estradiol levels correlate well with successful fertilization following ART. Mitochondria are the central sites for steroid hormone biosynthesis. The first and rate-limiting step in the biosynthesis of steroid hormones occurs in the mitochondria of granulosa cells. In the present study, we hypothesized that the mitochondria in granulosa cells are critical for maintaining oocyte quality and fertility capacity. This study aims to clarify the relationship between mitochondrial function and granulosa cell steroidogenesis, and the relationship between hormone levels and fertility capacity. Sera, follicular fluids and granulosa cells were obtained from individuals undergoing IVF-ET treatment. The oocyte numbers, oocyte quality, fertilization rate, and pregnancy rate were also recorded. The patients who provided the granulosa cells were further classified into four groups: endometriosis, ovarian endometrioma, endometriosis without ovarian endometrioma, and polycystic ovary syndrome (PCOS); patients with other female factor infertility and male factor infertility were used as controls. We measured the levels of estradiol (E2) by radioimmunoassay. Concurrently, we analyzed the mitochondrial mass and membrane potential, and apoptosis by flow cytometry using nonyl acridine orange, TMRE, Annexin V-FITC and PI. Mitochondrial morphology was visualized by transfection with pLV-mitoDsRed. In addition, we assessed the protein levels of steroidogenic enzymes, steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) by Western blot. The results showed significantly decreased serum E2 and follicular E2 levels, and decreased IVF outcomes, in the patients with endometriosis. Reduced mitochondrial mass and decreased mitochondrial membrane potential were correlated with lower E2. Furthermore, a significant decrease in StAR and 3β-HSD was found in patients with ovarian endometrioma. The enzyme levels of StAR and 3β-HSD were highly correlated with E2 levels. Finally, elevated cumulus cell apoptosis was found in the patient group with ovarian endometrioma and PCOS. In conclusion, mitochondrial dysfunction of human granulosa cells may contribute to the decline of steroidogenesis, decreased fertilization rate, oocyte maturation rate, and oocyte quality, and it can ultimately jeopardize fertility.
- MeSH
- apoptóza MeSH
- biologické modely MeSH
- cysty patologie MeSH
- dospělí MeSH
- endometrióza krev komplikace patologie MeSH
- estradiol krev MeSH
- fertilita * MeSH
- fertilizace in vitro MeSH
- folikulární buňky metabolismus MeSH
- folikulární tekutina metabolismus MeSH
- kumulární buňky metabolismus MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- oocyty metabolismus MeSH
- progesteron krev MeSH
- steroidy biosyntéza MeSH
- syndrom polycystických ovarií krev komplikace patologie MeSH
- těhotenství MeSH
- výsledek těhotenství MeSH
- ženská infertilita krev patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland's role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.
- MeSH
- afekt * MeSH
- cvičení * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nadledviny metabolismus MeSH
- postmenopauza * MeSH
- projektivní techniky MeSH
- psychoterapie * MeSH
- senioři MeSH
- steroidy biosyntéza MeSH
- určení symptomu MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has become apparent that those compounds that naturally occur in animals can also be found as natural constituents of plants and vice versa, i.e., they have essentially the same fate in the majority of living organisms. This review summarizes the current state of knowledge on the occurrence of animal steroid hormones in the plant kingdom, particularly focusing on progesterone, testosterone, androstadienedione (boldione), androstenedione, and estrogens.
- MeSH
- androstadieny metabolismus MeSH
- androstendion biosyntéza MeSH
- biosyntetické dráhy MeSH
- estrogeny biosyntéza MeSH
- fytosteroly metabolismus MeSH
- progesteron biosyntéza MeSH
- rostliny metabolismus MeSH
- steroidy biosyntéza MeSH
- testosteron biosyntéza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Because of the deep involvement of granulosa cells in the processes surrounding the cycles of menstruation and reproduction, there is a great need for a deeper understanding of the ways in which they function during the various stages of those cycles. One of the main ways in which the granulosa cells influence the numerous sex associated processes is hormonal interaction. Expression of steroid sex hormones influences a range of both primary and secondary sexual characteristics, as well as regulate the processes of oogenesis, folliculogenesis, ovulation, and pregnancy. Understanding of the exact molecular mechanisms underlying those processes could not only provide us with deep insight into the regulation of the reproductive cycle, but also create new clinical advantages in detection and treatment of various diseases associated with sex hormone abnormalities. We have used the microarray approach validated by RT-qPCR, to analyze the patterns of gene expression in primary cultures of human granulosa cells at days 1, 7, 15, and 30 of said cultures. We have especially focused on genes belonging to ontology groups associated with steroid biosynthesis and metabolism, namely "Regulation of steroid biosynthesis process" and "Regulation of steroid metabolic process". Eleven genes have been chosen, as they exhibited major change under a culture condition. Out of those, ten genes, namely STAR, SCAP, POR, SREBF1, GFI1, SEC14L2, STARD4, INSIG1, DHCR7, and IL1B, belong to both groups. Patterns of expression of those genes were analyzed, along with brief description of their functions. That analysis helped us achieve a better understanding of the exact molecular processes underlying steroid biosynthesis and metabolism in human granulosa cells.
- MeSH
- buněčné kultury metody MeSH
- folikulární buňky cytologie metabolismus MeSH
- genové regulační sítě MeSH
- kultivované buňky MeSH
- lidé MeSH
- metabolické sítě a dráhy * MeSH
- regulace genové exprese MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese metody MeSH
- steroidy biosyntéza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In vivo, resumption of oocyte meiosis occurs in large ovarian follicles after the preovulatory surge of luteinizing hormone (LH). The LH surge leads to the activation of a broad signaling network in mural granulosa cells equipped with LH receptors. The signals generated in the mural granulosa cells are further augmented by locally produced peptides or steroids and transferred to the cumulus cell compartment and the oocyte itself. Over the last decade, essential progress has been made in the identification of molecular events associated with the final maturation and ovulation of mammalian oocytes. All new evidence argues for a multiple roles of mitogen-activated protein kinase 3/1 (MAPK3/1) in the gonadotropin-induced ovulation processes. However, the knowledge of gonadotropin-induced signaling pathways leading to MAPK3/1 activation in follicular cells seems limited. To date, only the LH-induced transactivation of the epidermal growth factor receptor/MAPK3/1 pathway has been described in granulosa/cumulus cells even though other mechanisms of MAPK3/1 activation have been detected in other types of cells. In this review, we aimed to summarize recent advances in the elucidation of gonadotropin-induced mechanisms leading to the activation of MAPK3/1 in preovulatory follicles and cultured cumulus-oocyte complexes and to point out a specific role of this kinase in the processes accompanying final maturation of the mammalian oocyte.
- MeSH
- folikulární buňky metabolismus MeSH
- MAP kinasový signální systém genetika MeSH
- meióza fyziologie MeSH
- mitogenem aktivovaná proteinkinasa 1 metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 3 metabolismus MeSH
- mutace MeSH
- myši MeSH
- oocyty fyziologie MeSH
- steroidy biosyntéza MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
CONTEXT: Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. OBJECTIVE: To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. PATIENTS: 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. METHODS: SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). RESULTS: Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. CONCLUSIONS: Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations.
- MeSH
- energetický metabolismus fyziologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- mozkový neurotrofický faktor fyziologie MeSH
- mutace * MeSH
- nádorové buněčné linie MeSH
- rodokmen MeSH
- steroidogenní faktor 1 genetika MeSH
- steroidy biosyntéza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Primary adrenal insufficiency (PAI) is a rare condition in childhood which is either inherited (mostly) or acquired. It is characterized by glucocorticoid and maybe mineralocorticoid deficiency. The most common form in children is 21-hydroxylase deficiency, which belongs to the steroid biosynthetic defects causing PAI. Newer forms of complex defects of steroid biosynthesis are P450 oxidoreductase deficiency and (apparent) cortisone reductase deficiency. Other forms of PAI include metabolic disorders, autoimmune disorders and adrenal dysgenesis, e.g. the IMAGe syndrome, for which the underlying genetic defect has been recently identified. Newer work has also expanded the genetic causes underlying isolated, familial glucocorticoid deficiency (FGD). Mild mutations of CYP11A1 or StAR have been identified in patients with FGD. MCM4 mutations were found in a variant of FGD in an Irish travelling community manifesting with PAI, short stature, microcephaly and recurrent infections. Finally, mutations in genes involved in the detoxification of reactive oxygen species were identified in patients with unsolved FGD. Most mutations were found in the enzyme nicotinamide nucleotide transhydrogenase, which uses the mitochondrial proton pump gradient to produce NADPH. NADPH is essential in maintaining high levels of reduced forms of antioxidant enzymes for the reduction of hydrogen peroxide. Similarly, mutations in the gene for TXNRD2 involved in this system were found in FGD patients, suggesting that the adrenal cortex is particularly susceptible to oxidative stress.
- MeSH
- 11-beta-hydroxysteroid dehydrogenasy nedostatek MeSH
- adrenální insuficience diagnóza etiologie metabolismus terapie MeSH
- dítě MeSH
- glukokortikoidy nedostatek MeSH
- hirzutismus komplikace vrozené terapie MeSH
- kojenec MeSH
- lidé MeSH
- poruchy sexuálního vývoje s karyotypem 46, XX komplikace terapie MeSH
- předškolní dítě MeSH
- steroidy biosyntéza MeSH
- vrozené poruchy metabolismu steroidů komplikace terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Cytochromy P450 (CYPs) jsou enzymy, které se podílí nejen na metabolizmu léčiv, ale také na přeměně řady endogenních látek, mj. cholesterolu, který hraje v lidském organizmu významnou roli. V případě dysfunkce těchto enzymů mohou nastat závažná onemocnění, případně komplikace při léčbě. Tento článek se zabývá nejen samotným cholesterolem, ale především přehledem poruch enzymů metabolizujících cholesterol, a rovněž terapií následků enzymových insuficiencí. Léčba onemocnění tohoto typu spočívá především v substituční terapii, nicméně, i bez včasného vyšetření jednotlivých markerů nemusí být samotná léčba dostatečná.
Cytochrome P450 (CYPs) are enzymes which are involved in drug metabolism and also in biotransformation of a variety of endogenous compounds incl. cholesterol, which plays an important role in human body. In the case of malfunction of these CYP enzymes, complications in the treatment of diseases can take place and/or enzymes can also cause various diseases itself. This paper deals with cholesterol, disorders of enzymes metabolizing cholesterol and consequences of therapies of enzyme insufficiency. Treatment of diseases of this type consists mainly in replacement therapy; however, without the early testing of the individual markers, the treatment may not be sufficient.
- MeSH
- anticholesteremika MeSH
- azetidiny farmakologie terapeutické užití MeSH
- cholesterol farmakologie metabolismus MeSH
- cholestyraminová pryskyřice farmakologie terapeutické užití MeSH
- deriváty kyseliny fibrové farmakologie terapeutické užití MeSH
- hormonální substituční terapie MeSH
- hypercholesterolemie farmakoterapie MeSH
- hypolipidemika MeSH
- lékové interakce MeSH
- lidé MeSH
- probiotika farmakologie terapeutické užití MeSH
- silymarin farmakologie terapeutické užití MeSH
- statiny farmakologie terapeutické užití MeSH
- steroidy biosyntéza metabolismus MeSH
- systém (enzymů) cytochromů P-450 farmakologie genetika metabolismus nedostatek MeSH
- vrozené poruchy metabolismu steroidů enzymologie farmakoterapie MeSH
- žlučové kyseliny a soli biosyntéza metabolismus škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH