Showing papers on "Steroid biosynthesis published in 2022"
TL;DR: This study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients and reveals close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs.
Abstract: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS. However, the mechanism of regulation and interaction between hyperandrogenism and ovulation abnormalities are not clear. To investigate androgen-related metabolic state in granulosa cells of PCOS patients, we identified the transcriptome characteristics of PCOS granulosa cells by RNA-seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) revealed that genes enriched in lipid metabolism pathway, fatty acid biosynthetic process and ovarian steroidogenesis pathway were abnormally expressed in PCOS granulosa cells in comparison with that in control. There are close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs. Furthermore, in vitro mouse follicle culture system was established to explore the effect of high androgen and its related metabolic dysfunction on follicular growth and ovulation. RT-qPCR results showed that follicles cultured with dehydroepiandrosterone (DHEA) exhibited decreased expression levels of cumulus expansion-related genes (Has2, Ptx3, Tnfaip6 and Adamts1) and oocyte maturation-related genes (Gdf9 and Bmp15), which may be caused by impaired steroid hormone synthesis and lipid metabolism, thus inhibited follicular development and ovulation. Furthermore, the inhibition effect of DHEA on follicle development and ovulation was ameliorated by flutamide, an androgen receptor (AR) antagonist, suggesting the involvement of AR signaling. In summary, our study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients.
9 citations
TL;DR: The current understanding of molecular pathogenesis of BCs, especially for luminal subtypes, and their therapeutics is highlighted, underlining that StAR could serve not only as a prognostic marker, but also as a therapeutic candidate, in the prevention and treatment of this life-threatening disease.
Abstract: Estrogen promotes the development and survival of the majority of breast cancers (BCs). Aromatase is the rate-limiting enzyme in estrogen biosynthesis, and it is immensely expressed in both cancerous and non-cancerous breast tissues. Endocrine therapy based on estrogen blockade, by aromatase inhibitors, has been the mainstay of BC treatment in post-menopausal women; however, resistance to hormone therapy is the leading cause of cancer death. An improved understanding of the molecular underpinnings is the key to develop therapeutic strategies for countering the most prevalent hormone receptor positive BCs. Of note, cholesterol is the precursor of all steroid hormones that are synthesized in a variety of tissues and play crucial roles in diverse processes, ranging from organogenesis to homeostasis to carcinogenesis. The rate-limiting step in steroid biosynthesis is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process that is primarily mediated by the steroidogenic acute regulatory (StAR) protein. Advances in genomic and proteomic technologies have revealed a dynamic link between histone deacetylases (HDACs) and StAR, aromatase, and estrogen regulation. We were the first to report that StAR is abundantly expressed, along with large amounts of 17β-estradiol (E2), in hormone-dependent, but not hormone-independent, BCs, in which StAR was also identified as a novel acetylated protein. Our in-silico analyses of The Cancer Genome Atlas (TCGA) datasets, for StAR and steroidogenic enzyme genes, revealed an inverse correlation between the amplification of the StAR gene and the poor survival of BC patients. Additionally, we reported that a number of HDAC inhibitors, by altering StAR acetylation patterns, repress E2 synthesis in hormone-sensitive BC cells. This review highlights the current understanding of molecular pathogenesis of BCs, especially for luminal subtypes, and their therapeutics, underlining that StAR could serve not only as a prognostic marker, but also as a therapeutic candidate, in the prevention and treatment of this life-threatening disease.
6 citations
TL;DR: Exposure to cis-BF at environmentally relevant concentrations resulted in lipid metabolic disorder associated with nonalcoholic fatty liver disease of X. laevis, and the results provided new insight into the potential long-term hazards of pyrethroids.
Abstract: Pyrethroids, an effective and widely used class of pesticides, have attracted considerable concerns considering their frequent detection in environmental matrices. However, their potential health risks to amphibians remain unclear. In our study, female Xenopus laevis were exposed to 0, 0.06, and 0.3 μg/L typical pyrethroid, cis-bifenthrin (cis-BF), for 3 months. Elevated activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed, indicating an ongoing liver injury. Furthermore, exposure to cis-BF led to hyperlipidemia and lipid accumulation in the liver of Xenopus. The targeted lipidomic analysis further revealed that treatment with cis-BF perturbed liver steroid homeostasis, as evidenced by the enriched lipids in the steroid biosynthesis pathway. Consistent with the targeted lipidomic result, treatment with cis-BF changed the liver transcriptome profile with induction of 808 and 1230 differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis underlined the adverse effects of cis-BF exposure on steroid biosynthesis, primary bile acid biosynthesis, and the PPAR signaling pathway in the Xenopus liver. Taken together, our study revealed that exposure to cis-BF at environmentally relevant concentrations resulted in lipid metabolic disorder associated with nonalcoholic fatty liver disease of X. laevis, and our results provided new insight into the potential long-term hazards of pyrethroids.
5 citations
TL;DR: In this paper , the small VCP-interacting protein (SIP) was found to be a promising target for the regulation of ERAD, and it was shown that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves.
Abstract: Endoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2α, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion.
5 citations
TL;DR: It is shown that a plant mitochondrial steroidogenic pathway, dependent on an ADXR–ADX–P450 shuttle, is essential for female gametogenesis and early embryogenesis through a maternal effect.
Abstract: Significance Mitochondrial adrenodoxins (ADXs) are small iron–sulfur proteins that function as mobile shuttles transferring electrons. Their function has been largely known in animals, as they transfer electrons between an adrenodoxin reductase (ADXR) and mitochondrial P450s, which is a crucial step that leads to steroidogenesis. Here we show that a functional mitochondrial ADX–ADXR–P450 pathway is essential for steroid biosynthesis and that its function is required for plant sexual reproduction. Mitochondrial adrenodoxins (ADXs) are small iron–sulfur proteins with electron transfer properties. In animals, ADXs transfer electrons between an adrenodoxin reductase (ADXR) and mitochondrial P450s, which is crucial for steroidogenesis. Here we show that a plant mitochondrial steroidogenic pathway, dependent on an ADXR–ADX–P450 shuttle, is essential for female gametogenesis and early embryogenesis through a maternal effect. The steroid profile of maternal and gametophytic tissues of wild-type (WT) and adxr ovules revealed that homocastasterone is the main steroid present in WT gametophytes and that its levels are reduced in the mutant ovules. The application of exogenous homocastasterone partially rescued adxr and P450 mutant phenotypes, indicating that gametophytic homocastasterone biosynthesis is affected in the mutants and that a deficiency of this hormone causes the phenotypic alterations observed. These findings also suggest not only a remarkable similarity between steroid biosynthetic pathways in plants and animals but also a common function during sexual reproduction.
5 citations
TL;DR: In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women.
Abstract: Abstract Context Fasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact interplay between energy and steroid metabolism remains elusive. Women with polycystic ovary syndrome (PCOS) suffer from disturbed metabolism and androgen excess, while in women with anorexia nervosa, cortisol and androgen production are decreased. By contrast, starvation of steroidogenic cells shifts adrenal steroid biosynthesis toward enhanced androgen production. Aim This study investigated the effect of fasting on steroid production in healthy women. Methods Twenty healthy young women fasted for 48 hours; steroid profiles from plasma and urine samples were assessed at baseline, after 24 hours, and 48 hours by liquid and gas chromatography–mass spectrometry. Results Fasting did not change overall steroidogenesis, although it increased progestogen production and lowered relative mineralocorticoid, glucocorticoid, and androgen production. The largest decrease in urine metabolites was seen for β-cortol, dehydroepiandrosterone, and androstenediol; higher levels were found for pregnanediol in urine and progesterone and aldosterone in serum. Activity of 17α-hydroxylase/17,20-lyase (CYP17A1), essential for androgen biosynthesis, was decreased after fasting in healthy women as were 21-hydroxylase (CYP21A2) and 5α-reductase activities. By contrast, hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) activity for cortisol inactivation seemed to increase with fasting. Conclusion Significant changes in steroid metabolism occurred after 48 hours of fasting in healthy women. In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women.
3 citations
TL;DR: This study is of great significance for the industrial production of 7-DHC and steroid development for medical settings and the significant up-regulation of key genes transcriptional levels.
Abstract: 7-Dehydrocholesterol (7-DHC) is a widely used sterol and a precursor of several costly steroidal drugs. In this study, 7-DHC biosynthesis pathway was constructed and modified in Saccharomyces cerevisiae. Firstly, the biosynthesis pathway was constructed by knocking out the competitive pathway genes ERG5 and ERG6 and integrating two DHCR24 copies from Gallus gallus at both sites. Then, 7-DHC titer was improved by knocking out MOT3, which encoded a transcriptional repressor for the 7-DHC biosynthesis pathway. Next, by knocking out NEM1 and PAH1, 7-DHC accumulation was improved, and genes upregulation was verified by quantitative PCR (qPCR). Additionally, tHMG1, IDI1, ERG2, ERG3, DHCR24, POS5, and CTT1 integration into multi-copy sites was used to convert precursors to 7-DHC, and increase metabolic flux. Finally, qPCR confirmed the significant up-regulation of key genes transcriptional levels. In a 96 h shaker flask fermentation, the 7-DHC titer was 649.5 mg/L by de novo synthesis. In a 5 L bioreactor, the 7-DHC titer was 2.0 g/L, which was the highest 7-DHC titer reported to date. Our study is of great significance for the industrial production of 7-DHC and steroid development for medical settings.
3 citations
TL;DR: It was found that MG132 prevented the OC-mediated decrease in STAR protein levels following 8Br-cAMP stimulation, which suggested that proteins involved in steroid hormone production in addition to STAR are also affected by the OC mixture.
Abstract: Within Leydig cells, steroidogenesis is induced by the pituitary luteinizing hormone (LH). The binding of LH to its receptor increases cAMP production, which then activates the expression of genes involved in testosterone biosynthesis. One of these genes codes for the steroidogenic acute regulatory (STAR) protein. STAR is part of a complex that shuttles cholesterol, the precursor of all steroid hormones, through the mitochondrial membrane where steroidogenesis is initiated. Organochlorine chemicals (OCs) are environmental persistent organic pollutants that are found at high concentrations in Arctic areas. OCs are known to affect male reproductive health by decreasing semen quality in different species, including humans. We previously showed that an environmentally relevant mixture of OCs found in Northern Quebec disrupts steroidogenesis by decreasing STAR protein levels without affecting the transcription of the gene. We hypothesized that OCs might affect STAR protein stability. To test this, MA-10 Leydig cell lines were incubated for 6 h with vehicle or the OCs mixture in the presence or absence of 8Br-cAMP with or without MG132, an inhibitor of protein degradation. We found that MG132 prevented the OC-mediated decrease in STAR protein levels following 8Br-cAMP stimulation. However, progesterone production was still decreased by the OC mixture, even in the presence of MG132. This suggested that proteins involved in steroid hormone production in addition to STAR are also affected by the OC mixture. To identify these proteins, a whole cell approach was used and total proteins from MA-10 Leydig cells exposed to the OC mixture with or without stimulation with 8Br-cAMP were analyzed by 2D SDS-PAGE and LC-MS/MS. Bioinformatics analyses revealed that several proteins involved in numerous biological processes are affected by the OC mixture, including proteins involved in mitochondrial transport, lipid metabolism, and steroidogenesis.
3 citations
TL;DR: DM-208 as mentioned in this paper is a selective, nonsteroidal, oral CYP11A1 inhibitor that blocks the enzyme that catalyzes the first step of steroid hormone biosynthesis.
Abstract: Abstract Binding of steroid hormones to their cognate receptors regulates the growth of most prostate and breast cancers. We hypothesized that CYP11A inhibition might halt the synthesis of all steroid hormones, because CYP11A is the only enzyme that catalyses the first step of steroid hormone biosynthesis. We speculated that a CYP11A inhibitor could be administered safely provided that the steroids essential for life are replaced. Virtual screening and systematic structure–activity relationship optimization were used to develop ODM-208, the first-in-class, selective, nonsteroidal, oral CYP11A1 inhibitor. Safety of ODM-208 was assessed in rats and Beagle dogs, and efficacy in a VCaP castration-resistant prostate cancer (CRPC) xenograft mouse model, in mice and dogs, and in six patients with metastatic CRPC. Blood steroid hormone concentrations were measured using liquid chromatography-mass spectrometry. ODM-208 binds to CYP11A1 and inhibited its enzymatic activity. ODM-208 administration led to rapid, complete, durable, and reversible inhibition of the steroid hormone biosynthesis in an adrenocortical carcinoma cell model in vitro, in adult noncastrated male mice and dogs, and in patients with CRPC. All measured serum steroid hormone concentrations reached undetectable levels within a few weeks from the start of ODM-208 administration. ODM-208 was well tolerated with steroid hormone replacement. The toxicity findings were considered related to CYP11A1 inhibition and were reversed after stopping of the compound administration. Steroid hormone biosynthesis can be effectively inhibited with a small-molecule inhibitor of CYP11A1. The findings suggest that administration of ODM-208 is feasible with concomitant corticosteroid replacement therapy.
3 citations
TL;DR: In this article , a single-cell MA-10 Slip clone was derived from a murine Leydig cell tumor, and it was shown that exogenous cholesterol delivery by lipoproteins provided a significantly elevated steroid biosynthetic response.
Abstract: MA-10 cells, established 4 decades ago from a murine Leydig cell tumor, has served as a key model system for studying steroidogenesis. Despite a precipitous loss in their innate ability to respond to luteinizing hormone (LH), the use of a cell-permeable cAMP analog for induction ensured their continued use. In parallel, a paradigm that serum-free conditions are essential for trophic steroidogenic stimulation was rationalized. Through the selection of LH-responsive single-cell MA-10 Slip clones, we uncovered that Leydig cells remain responsive in the presence of serum in vitro and that exogenous cholesterol delivery by lipoproteins provided a significantly elevated steroid biosynthetic response (>2-fold). In scrutinizing the underlying regulation, systems biology of the MA-10 cell proteome identified multiple Rho-GTPase signaling pathways as highly enriched. Testing Rho function in steroidogenesis revealed that its modulation can negate the specific elevation in steroid biosynthesis observed in the presence of lipoproteins/serum. This signaling modality primarily linked to the regulation of endocytic traffic is evident only in the presence of exogenous cholesterol. Inhibiting Rho function in vivo also decreased hCG-induced testosterone production in mice. Collectively, our findings dispel a long-held view that the use of serum could confound or interfere with trophic stimulation and underscore the need for exogenous lipoproteins when dissecting physiological signaling and cholesterol trafficking for steroid biosynthesis in vitro . The LH-responsive MA-10 Slip clones derived in this study present a reformed platform enabling biomimicry to study the cellular and molecular basis of mammalian steroidogenesis.
2 citations
TL;DR: In this article , the effects of cis-bifenthrin on biosynthesis of adrenal steroids, as well as the potential mechanisms were investigated in human adrenocortical carcinoma (H295R) cells.
TL;DR: In this article, the authors demonstrate the potential of a novel Aggregated Biomarker Response (ABR) approach involving a comprehensive set of biomarkers to identify complex exposure and impacts on wild brown trout (Salmo trutta fario), using a small lowland river in Germany (Holtemme river in the Elbe river catchment) impacted by two wastewater treatment plants (WWTP) and diffuse agricultural runoff as a case study.
TL;DR: In this paper , the effects of sinapic acid phenethyl ester on the transcriptome of MA-10 Leydig cells were investigated by RNA-Seq, and the results indicated that sinapica and ferulic acid phenyl esters can improve cholesterol and steroid biosynthesis.
TL;DR: The recent advances in research on the reaction mechanisms of steroid hormone biosynthesis-related P450s, some of which catalyze unusual P450 reactions including C–C bond cleavage reactions by utilizing either a heme–peroxo anion species or compound I as an active oxidizing species are described.
Abstract: Steroid hormones modulate numerous physiological processes in various higher organisms. Research on the physiology, biosynthesis, and metabolic degradation of steroid hormones is crucial for developing drugs, agrochemicals, and anthelmintics. Most steroid hormone biosynthetic pathways, excluding those in insects, have been elucidated, and the roles of several cytochrome P450s (CYPs, P450s), heme (iron protoporphyrin IX)-containing monooxygenases, have been identified. Specifically, P450s of the animal steroid hormone biosynthetic pathways and their three dimensional structures and reaction mechanisms have been extensively studied; however, the mechanisms of several uncommon P450 reactions involved in animal steroid hormone biosynthesis and structures and reaction mechanisms of various P450s involved in plant and insect steroid hormone biosynthesis remain unclear. Recently, we determined the crystal structure of P450 responsible for the first and rate-determining step in brassinosteroids biosynthesis and clarified the regio- and stereo-selectivity in the hydroxylation reaction mechanism. In this review, we have outlined the general catalytic cycle, reaction mechanism, and structure of P450s. Additionally, we have described the recent advances in research on the reaction mechanisms of steroid hormone biosynthesis-related P450s, some of which catalyze unusual P450 reactions including C–C bond cleavage reactions by utilizing either a heme–peroxo anion species or compound I as an active oxidizing species. This review article is an extended version of the Japanese article, Structure and mechanism of cytochrome P450s involved in steroid hormone biosynthesis, published in SEIBUTSU BUTSURI Vol. 61, p. 189–191 (2021).
TL;DR: In this article , the authors applied ultra-performance liquid chromatography together with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), combined with chemometrics, for identifying metabolic changes regarding spawning broodstocks of Amur ide during migration.
Abstract: Amur ide (Leuciscus waleckii) lives in alkali-saline water (pH = 9.6) in the Lake Dali and spawns in freshwater rivers after migration annually. During spawning migrations, Amur ide not only experience osmoregulation modification from alkali-saline water to freshwater but also deal with energy prioritization for basal metabolism and gonadal development. To achieve an optimal cost-benefit balance, a series of metabolism modifications are needed. This study investigated the changing metabolite profiles that contribute to maintaining a balance of osmotic pressure and energy allocation for gonadal maturation. We applied ultra-performance liquid chromatography together with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), combined with chemometrics, for identifying metabolic changes regarding spawning broodstocks of Amur ide during migration. According to findings, there were 11,333 metabolites in Amur ide serum and 3,159 metabolites were found to change significantly during migration. Differentially expressed metabolites mainly affected the steroid hormone biosynthesis, the arachidonic acid metabolism, the biosynthesis of phenylalanine, tyrosine, and tryptophan, pyruvate metabolism, citrate cycle, as well as glycerophospholipid metabolism. Based on the enrichment analysis regarding metabolic pathways, biosynthesis of steroid hormone and arachidonic acid metabolism are two representative pathways, which are crucial for osmoregulation and gonadal maturation. The perturbation of some metabolites during migration was highlighted, which involves sexual maturation and reproduction, nitrogenous waste excretion, and energy allocation. The study assists in understanding the physiological plasticity exhibited by Amur ide during migratory spawning from a new perspective, which is useful as a scientific basis for the artificial breeding of Amur ide.
TL;DR: In this paper , the authors describe combined transcriptome profiling of asynchronously developing follicles in the same individual, showing that the levels of hsd17b12 and mPRγ mRNAs were much higher during the migratory nucleus stage, suggesting their respective involvement in the biosynthesis and functional pathway of the maturationinducing steroid 17α,20β-dihydroxy-4-pregnen-3-one.
TL;DR: In this article , miRNA-mRNA sequencing was performed on ovarian granulosa cells treated with kisspeptin in Tan sheep to determine the molecular pathways involved, and the sequencing results revealed that eight miRNAs significantly differed between the experimental and control groups.
Abstract: Simple Summary Neurons produce kisspeptin, a peptide hormone that stimulates the pituitary gland to produce gonadotropin and regulate reproductive development. Granulosa cells exist in the ovaries of female animals, secreting hormone receptors and regulating follicular maturation and hormonal balance. The mechanism of regulation of the function of granulosa cells by kisspeptin is still unclear. miRNA-mRNA sequencing was performed on ovarian granulosa cells treated with kisspeptin in Tan sheep to determine the molecular pathways involved. The sequencing results revealed that eight miRNAs significantly differed between the experimental and control groups. The results also indicated that several miRNAs and their target genes regulate steroid production and cell proliferation. This study’s findings will help further explore the molecular mechanism of kisspeptin in the regulation of the function of ovarian granulosa cells in Tan sheep. Abstract Kisspeptin is a peptide hormone encoded by the kiss-1 gene that regulates animal reproduction. Our studies revealed that kisspeptin can regulate steroid hormone production and promote cell proliferation in ovarian granulosa cells of Tan sheep, but the mechanism has not yet been fully understood. We speculated that kisspeptin might promote steroid hormone production and cell proliferation by mediating the expression of specific miRNA and mRNA in granulosa cells. Accordingly, after granulosa cells were treated with kisspeptin, the RNA of cells was extracted to construct a cDNA library, and miRNA-mRNA sequencing was performed. Results showed that 1303 expressed genes and 605 expressed miRNAs were identified. Furthermore, eight differentially expressed miRNAs were found, and their target genes were significantly enriched in progesterone synthesis/metabolism, hormone biosynthesis, ovulation cycle, and steroid metabolism regulation. Meanwhile, mRNA was significantly enriched in steroid biosynthesis, IL-17 signaling pathway, and GnRH signaling pathway. Integrative analysis of miRNA-mRNA revealed that the significantly different oar-let-7b targets eight genes, of which EGR1 (early growth response-1) might play a significant role in regulating the function of granulosa cells, and miR-10a regulates lipid metabolism and steroid hormone synthesis by targeting HNRNPD. Additionally, PPI analysis revealed genes that are not miRNA targets but crucial to other biological processes in granulosa cells, implying that kisspeptin may also indirectly regulate granulosa cell function by these pathways. The findings of this work may help understand the molecular mechanism of kisspeptin regulating steroid hormone secretion, cell proliferation, and other physiological functions in ovarian granulosa cells of Tan sheep.
TL;DR: A model in which DHCR24 plays an important part in regulating ESCs differentiation by curing the activities of steroid hormones synthesis is lead to.
Abstract: Spermatogonia stem cells (SSCs) have become one of the hotspots in modern life science research in the 21st century because of the broad application prospects in medicine, biology and animal breeding. Studies have shown that steroid biosynthesis signaling pathway is involved in the
multiple cell differentiation process, but the formation of SSCs is not clear. DHCR24 proved in our outcome that it play an important part in steroid biosynthesis. Without the absent of DHCR24, CYP7A1 and PTCH2 are not keeping the expression of downstream genes. It’s the downregulation
of the steroid biosynthesis pathway which lead to the decrement. What’s more, the steroid biosynthesis pathway could make it easy for the differentiation of embryonic stem cells (ESCs) is proved by qRT-PCR, immunofluorescence and flow cytometry analysis. All things considered. The above
mentioned outcomes has lead to a model in which DHCR24 plays an important part in regulating ESCs differentiation by curing the activities of steroid hormones synthesis.
TL;DR: The expression of genes belonging to ontology groups associated with steroid biosynthesis and metabolism, such as “cholesterol biosynthetic process” (GO:0006695), “regulation of lipid metabolic process, response to insulin, and response to lipopolysaccharide, were analyzed by using the microarray approach as mentioned in this paper .
Abstract: Abstract The ovary is commonly known as an endocrine gland responsible for sex steroid production. One of the outstanding cells in ovarian microenvironment - granulosa cells (GCs) are responsible for converting the androgens to estrogens during follicular growth and secreting progesterone after ovulation. These secretory processes within the ovary are directly involved in hormonal signaling pathways, and they depend on different stages of cholesterol and lipid biosynthesis during the ovarian cycle. The understating of the regulation and further investigation into the processes taking part in ovary will expose new clinical advantages in detection and treatment of female reproductive system diseases associated with sex hormone abnormalities. The expression of genes belonging to ontology groups associated with steroid biosynthesis and metabolism, such as “cholesterol biosynthetic process” (GO:0006695, “regulation of lipid biosynthetic process” (GO:0046890), “regulation of lipid metabolic process” (GO:0019216), “response to insulin” (GO:0032868) and “response to lipopolysaccharide” (GO:0032496) were analyzed by using the microarray approach. The patterns of gene expression in human GCs at days 1-day, 7-day, 15-day, and 30-day of primary in vitro culture have been analyzed. Based on the microarray results, a group of upregulated genes have been selected: CCL20, CXCL5, STAR, MSMO1, and AADAC. The genes STAT5B, OPA3, PPARG, PROX1, and SEC14L2 were decreased across all the experimental groups during the 30-day cell cultivation period. These results suggest that, the GCs in cell culture under in vitro express steroidogenic markers and it is important to understand associations with lipid and liposaccharide synthesis relative to reproductive medicine.
TL;DR: Wang et al. as mentioned in this paper used RNA-Seq and lipidomics technology to profile the ovarian transcriptome and serum lipidomics after feeding four ARA supplemented diets (named CT, LT, MT and HT), and the differentially expressed genes (DEGs and key differential metabolites were identified.