- |||||||||| ODM-208 / Orion Corp, Merck (MSD)
Journal: Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology. (Pubmed Central) - Apr 8, 2024
Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.
- |||||||||| flutamide / Generic mfg.
Journal: Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish. (Pubmed Central) - Mar 18, 2024
Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes...Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.
- |||||||||| Journal: Cytochrome P450 genes expression in human prostate cancer. (Pubmed Central) - Mar 12, 2024
Therefore, the expression of CYPs is not directly associated with prostate cancer but is largely determined by genetic, epigenetic factors, as well as endogenous substrates and xenobiotics. The significant correlative relationship between CYPs and genes associated with cancer may indicate common regulatory pathways that may have a synergistic effect on the tumor, ensuring the survival of cancer cells.
- |||||||||| Journal: New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis. (Pubmed Central) - Mar 11, 2024
The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish.
- |||||||||| Journal: Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. (Pubmed Central) - Feb 28, 2024
Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS.
- |||||||||| tamoxifen / Generic mfg.
Journal: Estrogen Signaling Inhibits the Expression of anti-M (Pubmed Central) - Feb 14, 2024
Using the cyp17a1- and cyp19a1a-deficient zebrafish, we provide evidence to show that the upregulated expression of amh and gsdf due to the compromised estrogen signaling probably determines their sexual fate towards testis differentiation. Collectively, our data suggest that estrogen signaling inhibits the expression of amh and gsdf during the critical time of sexual fate determination, which may broaden the scope of sex steroid hormones in regulating gonadal sex differentiation in fish.
- |||||||||| ODM-208 / Orion Corp, Merck (MSD)
Journal: Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer. (Pubmed Central) - Feb 13, 2024
Collectively, our data suggest that estrogen signaling inhibits the expression of amh and gsdf during the critical time of sexual fate determination, which may broaden the scope of sex steroid hormones in regulating gonadal sex differentiation in fish. In the Original Article, "Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer", originally published December 26, 2023 (DOI: https://doi.org/10.1056/EVIDoa2300171), in the Abstract, under "Background", the sentence "ODM-208, a novel inhibitor of cytochrome P450 17A1
- |||||||||| Preclinical, Journal: Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. (Pubmed Central) - Feb 8, 2024
ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.
- |||||||||| R-Spondin1 (NU-206) / ARCA Biopharma
Journal: Comparative transcriptome analysis of ovaries and testes reveals sex-biased genes and pathways in zebrafish. (Pubmed Central) - Feb 5, 2024
Finally, the expression levels of 14 sex-biased DEGs (cdc20, ccnb1, ypel3, chn1, bmp15, rspo1, tnfsf10, egfra, acta2, cox8a, gsdf, dmrt1, star, and cyp17a1) associated with the enriched pathways were subjected to further validation through qRT-PCR. The data acquired from these investigations offer valuable resources to support further exploration of the mechanisms governing sexual dimorphism and gonadal development in zebrafish.
- |||||||||| Preclinical, Journal: In vitro effects of uncarboxylated osteocalcin on buffalo Leydig cell steroidogenesis. (Pubmed Central) - Feb 2, 2024
When these cells were cultured and incubated with varying levels of UcOCN (6, 12, 24, and 48 ng/ml) and LH, there was a significant (P?<?0.01) increase in testosterone production and up-regulation (P?<?0.05) of CYP11A1, CYP17A1, HSD3?1 and HSD3?6 gene expression. In summary, the present study underscored the effects of UcOCN on testosterone biosynthesis, expression of crucial steroidogenic genes and interaction with GPRC6A receptors in buffalo Leydig cells, emphasizing its potential implications in andrology.
- |||||||||| progesterone / Generic mfg.
Journal: Luteinizing Hormone Surge-Induced Kr (Pubmed Central) - Jan 23, 2024
Overexpression of Klf4 decreased basal and Sf1-induced Cyp17A1 expressions and increased progesterone secretion...Taken together, these data indicate that the Cyp17A1 gene may be one of the downstream targets of Klf4, which is induced by LH in preovulatory GCs. This information may help in identifying potential targets for preventing the molecular changes occurring in hyperandrogenic disorders.
- |||||||||| Journal: Prostate cancer androgen biosynthesis relies solely on CYP17A1 downstream metabolites. (Pubmed Central) - Jan 12, 2024
Precursor steroids upstream of DHEA were converted down the first steps of the alternative DHT biosynthesis pathway, but did not proceed through to active androgen generation. Comprehensive steroid flux analysis of (CR)PC cells provides strong evidence against intratumoral de novo androgen biosynthesis and demonstrates that androgen precursor steroids downstream of CYP17A1 activities constitute the major source of intracrine androgen generation.
- |||||||||| Efficacy of NGS Testing for Pediatric Endocrine Related Disease (MTCC - Exhibit Halls DE) - Jan 10, 2024 - Abstract #ACMG2024ACMG_882;
Our data demonstrate that while providers prefer to order panel testing, the diagnostic yield is lower relative to ES. Although guidelines provide decision trees for testing approaches utilizing gene-specific panel testing in affected individuals, 14% of our cases harbored large CNVs outside of the tested regions, suggesting a genome wide approach may capture more diagnoses.
- |||||||||| Preclinical, Journal: l-valine supplementation disturbs vital molecular pathways and induces apoptosis in mouse testes. (Pubmed Central) - Jan 8, 2024
RT-qPCR validated 8 of 9 DEGs (Cd36, Scd1, Insl3, Anxa5, Lcn2, Hsd17b3, Cyp11a1, Cyp17a1 and Agt) to be decreased significantly, consistent with RNA-seq results. Taken together, l-valine treatment could disturb multiple signaling pathways (autophagy and RNA methylation etc.), and induce apoptosis to destroy the tissue structure of mouse testis.
- |||||||||| progesterone / Generic mfg.
Preclinical, Journal: Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone. (Pubmed Central) - Dec 28, 2023
Collectively, these findings imply that progesterone suppresses spinal astrocyte activation via 5?-reductase activity during the maintenance phase of chronic pain and has an analgesic impact on the mechanical allodynia associated with the growing neuropathy. Progesterone, however, stimulates spinal astrocytes during the induction stage of peripheral neuropathy and boosts the allodynic impact caused by CCI through early spinal P450c17 activation.
- |||||||||| Journal: REVERBA couples the circadian clock to Leydig cell steroidogenesis. (Pubmed Central) - Dec 26, 2023
Moreover, this REVERBA-dependent stimulation had a clear impact on testosterone production in the culture medium, underscoring REVERBA's involvement in the circadian regulation of testosterone. This study indicates that REVERBA, in addition to being a core component of the cellular clock, plays a key role in regulating androgen production in Leydig cells by influencing the transcription of critical steroidogenesis-related genes.
- |||||||||| progesterone / Generic mfg.
Preclinical, Journal: Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats. (Pubmed Central) - Dec 17, 2023
TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries...TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.
- |||||||||| Journal: Taste receptor type 1 member 3 regulates Western diet-induced male infertility. (Pubmed Central) - Nov 26, 2023
Additionally, we analyzed the public human dataset to assess the clinical implications of our findings and confirmed a significant association between TAS1R3 and male-infertility-related diseases. Our findings suggest that TAS1R3 regulates WD-induced male reproductive impairment via the AMPK/NR4A1 signaling and can be a novel therapeutic target for male infertility.
- |||||||||| Journal: Association of Metabolic and Endocrine Disorders with Bovine Ovarian Follicular Cysts. (Pubmed Central) - Nov 14, 2023
The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis linked the ovarian steroidogenesis pathway, especially the STAR, 3?-HSD, CYP11A1 and CYP17A1 genes, to the formation of follicular cysts (p < 0.01). These results indicated that hormone metabolic disorders and abnormal expression levels of hormone synthesis pathway genes are associated with the formation of bovine ovarian follicular cysts.
- |||||||||| temozolomide / Generic mfg.
Development of a novel CYP17A1-targeted inhibitor for glioblastoma (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_609;
Glioblastoma (GBM) is a highly aggressive and invasive brain tumor, resistant to current standard treatments, including temozolomide (TMZ) and radiotherapy...In vivo testing in the TMZ-resistant GBM orthotopic mouse model also showed promising anti-tumor activity, with treated mice demonstrating increased survival times compared to controls. In conclusion, our findings suggest that this drug targeting both CYP17A1 and HDAC6 presents a potential breakthrough in GBM-targeted therapy, addressing the pervasive issue of TMZ resistance.
- |||||||||| Preclinical, Review, Journal: Diuron-induced fetal Leydig cell dysfunction in in vitro organ cultured fetal testes. (Pubmed Central) - Nov 11, 2023
However, 3-?HSD, an FLC and ALC marker, was consistently maintained upon exposure to diuron in fetal testes compared to non-treated groups. In conclusion, our study demonstrates that diuron negatively impacts Fetal Leydig cell development, although it does not affect germ and Sertoli cells.
- |||||||||| Journal: The food safety assessment of all-female common carp (Cyprinus carpio) (cyp17a1+/-;XX genotype) generated using genome editing technology. (Pubmed Central) - Nov 6, 2023
Compared with those fed control carp, the rats fed AF common carp exhibited no significant difference in body weight, food intake, feed conversion ratio, hematology, serum biochemistry, urine test, relative organ weight, gross necropsy, and histopathological examination. This is the first food safety assessment of the farmed fish strain cultured using CRISPR/Cas9, which will further advance the fishery development of genome-edited animals.
- |||||||||| progesterone / Generic mfg.
Journal: Steroid 17?-hydroxylase/17, 20-lyase (cytochrome P450 17A1). (Pubmed Central) - Nov 3, 2023
Cytochrome P450 (P450) 17A1 plays a key role in steroidogenesis, in that this enzyme catalyzes the 17?-hydroxylation of both pregnenolone and progesterone, followed by a lyase reaction to cleave the C-20 land C-21 carbons from each steroid...Historic assay approaches are reviewed. Some information is also provided about outstanding questions in the research field, including catalytic mechanisms and searches for selective inhibitors.
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