Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Therapeutic potential of enzymes, neurosteroids, and synthetic steroids in neurodegenerative disorders: A critical review","authors":"Refik Servi , Ramazan Fazıl Akkoç , Feyza Aksu , Süleyman Servi","doi":"10.1016/j.jsbmb.2025.106766","DOIUrl":"10.1016/j.jsbmb.2025.106766","url":null,"abstract":"<div><div>Neurodegenerative disorders present a significant challenge to healthcare systems, mainly due to the limited availability of effective treatment options to halt or reverse disease progression. Endogenous steroids synthesized in the central nervous system, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), progesterone (PROG), and allopregnanolone (ALLO), have been identified as potential therapeutic agents for neurodegenerative diseases. Neurosteroids such as ALLO, DHEA, and PROG, as well as their synthetic analogs like Ganaxolene, Fluasterone, and Olexoxime, offer promising effects for conditions such as Alzheimer's disease (AD) and depression. Moreover, Brexanolone and Ganaxolone are synthetic steroids approved for the treatment of postpartum depression and epilepsy, respectively. Neurosteroids such as ALLO are crucial in modulating GABAergic neurotransmission and reducing neuroinflammation. These compounds enhance the activity of GABA-A receptors, leading to increased inhibitory signaling in the brain, which can help regulate mood, cognition, and neuroprotection. Small clinical trials and observational studies indicate that ALLO may have cognitive benefits, but no large-scale, definitive meta-analysis confirms a 20 % improvement in AD patients. Mitochondrial dysfunction plays a vital role in the pathogenesis of numerous neurological diseases due to the high-energy demand and sensitivity of neurons to oxidative stress. Reduced mitochondrial function leads to amyloid-beta plaques and tau tangles accumulation in AD. In Parkinson's disease (PD), mitochondrial dysfunction resulting from the PINK1 or Parkin genes leads to energy deficiencies and the accumulation of toxic byproducts. Mutations in genes such as SOD1, C9orf72, and TDP-43 have been associated with mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS). Moreover, studies on these neurodegenerative diseases suggest that inflammation is not merely a consequence of neurodegeneration but is also an essential factor in this process. Many neurological disorders involve multifaceted interactions between genetics, the environment, and immune responses, making it difficult to pinpoint their exact causes. Future research aims to overcome these hurdles through genetic advances, regenerative medicine, and personalized therapies. Cutting-edge technologies such as artificial intelligence and high-throughput screening are expected to accelerate drug discovery and improve diagnostic accuracy. Increasing collaboration between interdisciplinary fields such as bioinformatics, neuroscience, and immunology will lead to innovative treatment strategies. This comprehensive review discusses the therapeutic effects of enzymes, neurosteroids, and synthetic steroids in different neurodegenerative diseases, particularly AD, PD, ALS, and MS. Potential challenges in the therapeutic use of neurosteroids, such as the limited bioavailability and off-target effects of synthetic steroids, are a","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106766"},"PeriodicalIF":2.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the effects of estrogens on endometrial cancer cells of different grades","authors":"Renata Pavlič,&nbsp;Maja Novak Pušić,&nbsp;Tea Lanišnik Rižner","doi":"10.1016/j.jsbmb.2025.106762","DOIUrl":"10.1016/j.jsbmb.2025.106762","url":null,"abstract":"<div><div>Endometrial cancer (EC) is the most common gynecological malignancy in the Western world. The molecular basis and effects of various agents are frequently studied in model EC cell lines, but the most commonly used cell lines Ishikawa, HEC-1-A, RL95–2 and KLE have not been thoroughly and systematically investigated. We characterized EC cell lines of different grades by reassessing the expression of estrogen receptors ERα, ERβ, and GPER by qPCR and Western blot and investigated the effects of estrogens, estrone-sulfate, estrone and estradiol on their proliferation, migration, and clonogenicity. Estradiol promoted the proliferation of grade 1 Ishikawa EC cells and grade 2 RL95–2 cells. Estrone and estrone sulfate also stimulated the proliferation of Ishikawa, showed a tendency to increase the proliferation of HEC-1-A and RL95–2 cells, but decreased the proliferation of KLE. Estrogens had no effect on the migration and clonogenicity of these four EC cell lines, however, there was a trend toward a smaller colony area for cells incubated with higher estrogen concentrations. We have previously shown that in EC estradiol forms from inactive estrone sulfate via the sulfatase pathway. This study showed that estrogens significantly promote the proliferation of grade 1 Ishikawa EC cells, and grade 2 RL95–2 and decrease the proliferation of grade 3 KLE cells. These differences in proliferation were associated with ERα positivity of Ishikawa cells and GPER expression in other cells.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106762"},"PeriodicalIF":2.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular fluid concentrations of the vitamin D metabolite 24,25(OH)2D3 are positively associated with live birth rate after assisted reproductive technology","authors":"Ireen Kooij ,&nbsp;Rune Holt ,&nbsp;Li Juel Mortensen ,&nbsp;Mette Lorenzen ,&nbsp;Ursula Bentin-Ley ,&nbsp;Hans Krog ,&nbsp;Anders Hayden Berg ,&nbsp;Anders Juul ,&nbsp;Stine Gry Kristensen ,&nbsp;Anne Jørgensen ,&nbsp;Martin Blomberg Jensen","doi":"10.1016/j.jsbmb.2025.106764","DOIUrl":"10.1016/j.jsbmb.2025.106764","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between concentrations of vitamin D metabolites in follicular fluid and outcome of assisted reproductive technology (ART) treatment.</div></div><div><h3>Design</h3><div>Prospective cohort study including 116 women undergoing <em>in vitro</em> fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) treatment.</div></div><div><h3>Results</h3><div>All measured vitamin D metabolites 25OHD₃, 1,25(OH)₂D₃ and 24,25(OH)₂D₃ are detectable in follicular fluid. Follicular fluid concentration of the 24,25(OH)₂D₃ metabolite was higher than corresponding serum values, while the opposite phenomenon was observed for the 1,25(OH)₂D₃ metabolite. Local conversion is plausible as the vitamin D activating enzymes (CYP2R1 and CYP27B1) as well as the vitamin D receptor (VDR) are highly expressed in the developing follicle. Women who achieved a live birth had 29 % higher 24,25(OH)₂D₃ and 15 % higher 25OHD₃ concentrations in their follicular fluid (18 ± 7.9 versus 14 ± 6.2 nmol/L, p = 0.008 and 71 ± 22 versus 62 ± 18 nmol/L, p = 0.025, respectively) compared to women not achieving a live birth. Moreover, women with a low (≤ 15 %) follicular fluid 1,25(OH)₂D₃/24,25(OH)₂D₃ ratio had a higher live birth rate compared to women with a medium (16–84 %) or high (≥ 85 %) ratio (live birth rate: 53 % vs 29 % and 12 %, respectively, p = 0.032).</div></div><div><h3>Conclusion</h3><div>This study reveals that high levels of 24,25(OH)₂D₃ and low levels of the 1,25(OH)₂D₃/24,25(OH)₂D₃ ratio in follicular fluid are associated with increased live birth rates in women undergoing IVF/ICSI treatment. Conversion of vitamin D metabolites systemically or in the ovarian follicle may affect ART outcome. Further studies are warranted to support the findings from this pilot study and identify regulators of ovarian vitamin D metabolites.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106764"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification and biochemical characterization of mutant ligand binding domain of human estrogen receptor α protein","authors":"Murugesan Palaniappan ,&nbsp;Kurt M. Bohren","doi":"10.1016/j.jsbmb.2025.106763","DOIUrl":"10.1016/j.jsbmb.2025.106763","url":null,"abstract":"<div><div>The acquisition of mutations in the estrogen receptor alpha (ERα) gene (ESR1) is a key driver in the development of resistance to current endocrine therapy in breast cancer. Clinical studies have shown that ESR1 mutations are frequently observed in patients with metastatic ER-positive breast cancer and are associated with poor survival. Activating ESR1 somatic mutations, particularly Y537S and D538G, drive estrogen-independent activities in cell-based studies and these mutant receptors are less sensitive to current endocrine therapies. Here, we describe the bacterial expression and purification of the ligand binding domains of wild-type, Y537S, and D538G human ERα proteins. The biochemical activities of these domains were confirmed by homogeneous time-resolved fluorescence and polar screen ERα competition assays. The wild-type domain binds to coactivator peptides only in the presence of the ligand estradiol, whereas the Y537S or D538G domains bind coactivator peptides spontaneously even without estradiol, with the Y537S domain showing higher affinity. Thermal shift assays showed that the mutations stabilized these domains. Our purified human ERα wild-type, Y537S, and D538G ligand binding domains recapitulate the biological activities ascribed to the full-length proteins and can therefore be used for small molecule screens that seek to discriminate between wild-type and mutant ERα.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106763"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of different vitamin D forms and fortified foods to vitamin D intake in Europe: A narrative review","authors":"Maaike J. Bruins","doi":"10.1016/j.jsbmb.2025.106761","DOIUrl":"10.1016/j.jsbmb.2025.106761","url":null,"abstract":"<div><div>In the current narrative review, the bioavailability of the main vitamin D forms is evaluated. The mean intakes and main contributing forms of vitamin D in the European diet are estimated, as well as the major contributing dietary sources. The literature is reviewed for studies reporting on the proportion of users and non-users of fortified food with vitamin D intakes below reference intakes. In addition, the availability of vitamin D-fortified prepackaged retail products and fortification levels in the European market is assessed. Previously, vitamins D2 and D3 forms were considered the primary forms in the diet. Recent analytical methods suggest that dietary 25(OH)D3, when adjusted for higher bioequivalence, significantly contributes to total vitamin D intakes. When also considering 25(OH)D3 from foods, the estimated vitamin D intake from an average European diet was 3.8 µg/d of total Vitamin D Equivalents: vitamin D3, vitamin D2 and 25(OH)D3, contributing about 71 %, 2 %, and 27 %, respectively. Animal foods, fortified fats and spreads contributed most to total intakes. Literature suggests that 94–100 % of Europeans aged ≥ 13 y fail to meet the vitamin D reference intake of 10 µg/d. About 98–100 % of vitamin D-fortified food users and 99–100 % of non-users in the UK and Netherlands consumed less than 10 µg/d of vitamin D. About 1.2 % of prepackaged foods and drinks were voluntary fortified with vitamin D, margarine and plant-based drinks providing most of the daily vitamin D. Encouraging fortification and other strategies may support closing the gap between current and recommended vitamin D intakes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106761"},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The distinctive P450 oxidoreductase (PORD) urinary steroid metabolome in the first week of life: Report of three cases with severe disorder","authors":"E.S. Baranowski ,&nbsp;J. Idkowiak ,&nbsp;J. Waterson ,&nbsp;A. D’Harlingue ,&nbsp;A.H. Olney ,&nbsp;H.E. Ivison ,&nbsp;B.A. Hughes ,&nbsp;J.W. Mueller ,&nbsp;W. Arlt ,&nbsp;C.H.L. Shackleton","doi":"10.1016/j.jsbmb.2025.106760","DOIUrl":"10.1016/j.jsbmb.2025.106760","url":null,"abstract":"<div><div>P450 oxidoreductase (POR) facilitates electron flux to type 2 microsomal P450 cytochrome enzymes (CYPs), including the adrenal steroidogenic enzymes CYP17A1 and CYP21A2. Due to the combined impairment of these enzymes, POR deficiency (PORD), an autosomal recessive condition, results in congenital adrenal hyperplasia characterised by combined glucocorticoid and postnatal sex steroid deficiency. This study focuses on urinary steroid excretion in infants affected by PORD in the first week of life. We report on three neonatal PORD cases from two families. One family had two affected babies born three years apart who were stillborn and first-day deceased, respectively. DNA sequencing revealed a homozygous 3 bp deletion in exon six leading to an glutamic acid deletion (p.[Glu217del]). Bladder contents were obtained from the stillborn baby, and excreted urine was obtained from the second baby. In a second family, their second affected newborn, antenatally diagnosed carrying the common homozygous p.(Ala287Pro) mutation, had urine collected daily during the first week of life. Steroid excretions were quantified by gas chromatography-mass spectrometry (GC-MS). The birth-day excretions were very similar in all babies. Most notable and unusual was a large excretion of unmetabolised corticosterone, suggesting inhibited catabolism to allow maximum active gluco- and mineralocorticoid availability at birth. Because CYP3A7 (16α-hydroxylase) requires POR, there was an almost complete absence of usually dominant 3β-hydroxy-Δ⁵ steroids (16α-OH-DHEA and 16α-OH-pregnenolone) and the usually characteristic precursor pregnenolone metabolite 5-pregnene-3β,20α-diol (pregnenediol, 5PD). In the baby sequentially studied over a week, we observed gradual maturation to the typical and familiar PORD neonatal metabolome. At the end of the period, the minimally catabolised corticosterone had diminished, and steroid excretion was completely dominated by 5PD, excreted as both mono- and disulphate conjugates. Whether this metabolome is distinctive of all PORD infants, not just those with severe manifestation, is not known. On the first day of life, standard diagnostic markers are compromised due to fetal-placental-maternal contribution and unique neonatal steroid metabolism. However, the Day 1 PORD steroid metabolome remains distinctive, and we propose using additional biochemical markers reflective of the near complete reduction of POR-dependent CYP3A7 (16α-hydroxylase) activity to improve diagnostic yield.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106760"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive survey of disease-causing missense mutations of the cholesterol synthesis enzyme NSDHL: Low temperature and a chemical chaperone rescue low protein expression of select mutants","authors":"Nicole M. Fenton,&nbsp;Laura J. Sharpe,&nbsp;Dylan M. Fitzsimmons,&nbsp;Isabelle M. Capell-Hattam,&nbsp;Andrew J. Brown","doi":"10.1016/j.jsbmb.2025.106758","DOIUrl":"10.1016/j.jsbmb.2025.106758","url":null,"abstract":"<div><div>Cholesterol is essential to human life. Perturbations to any of the 22 cholesterol synthesis enzymes can lead to devastating developmental diseases. Each enzyme is exquisitely regulated both transcriptionally and post-translationally, playing a critical role in providing cholesterol to cells. We examined 13 missense mutations and one deletion mutation in the cholesterol synthesis enzyme NSDHL (NAD(P) Dependent Steroid Dehydrogenase-Like), known to cause the X-linked developmental disorders CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome and CK syndrome. Little is known about the effect of these missense mutations on the stability and function of NSDHL. Here we show that protein expression levels were low for all mutants, but some could be rescued by a lower temperature (30°C <em>vs.</em> 37°C) and/or the chemical chaperone glycerol. Additionally, heat shock proteins 70 and 90 are needed for optimal NSDHL protein expression suggesting that disease mutations in NSDHL may interfere with this interaction, perhaps during translation resulting in lower protein synthesis. Our findings that these disease-causing mutations reduce NSDHL protein expression, but some respond to lower temperature and/or the chemical chaperone glycerol, can help inform future treatments for CHILD and CK syndrome.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106758"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High reliance on fortified foods when optimizing diets of adolescents in Sweden for adequate vitamin D intake and climate sustainability","authors":"André Hesselink ,&nbsp;Anna Winkvist ,&nbsp;Anna Karin Lindroos ,&nbsp;Patricia Eustachio Colombo ,&nbsp;Linnea Bärebring ,&nbsp;Elinor Hallström ,&nbsp;Hanna Augustin","doi":"10.1016/j.jsbmb.2025.106759","DOIUrl":"10.1016/j.jsbmb.2025.106759","url":null,"abstract":"<div><div>The global food system contributes roughly one-third of global greenhouse gas emissions (GHGEs) making shifts towards more sustainable food consumption an imperative. Such diets also need to factor in nutrient requirements and cultural acceptability. Our aim was to simulate dietary changes for adolescents in Sweden to achieve the recommended intake (RI) for vitamin D while factoring in additional nutrients, cultural acceptability and keeping the diet within planetary boundaries for climate change. A baseline diet was estimated from Sweden’s national dietary survey Riksmaten Adolescents 2016–17 (n = 3099, ages 11–18 years), which provided food intake via two 24-hour recalls. Intake data were linked to the Swedish Food Agency’s food composition database and GHGE estimates from the Research Institutes of Sweden’s (RISE) Food Climate Database. Linear programming was used to optimize the baseline diet to meet the RI for vitamin D (10 µg/day), reduce GHGEs to ≤ 1.7 kg CO₂-equivalents/person/day, and minimize dietary changes from baseline to factor in cultural acceptability. A second optimization included 25 additional nutrients requirements. Both optimized diets met their respective requirements reducing GHGEs by 54 % but relied heavily on milk and yoghurt (fortified by law), which provided &gt; 60 % of vitamin D intake. Both diets also required major shifts toward plant-based foods and the second optimization demanded a five-fold greater change in diet from baseline compared to first optimization. Results suggest that adolescents in Sweden can achieve RIs for vitamin D and other nutrients while greatly reducing diet-related GHGEs, though cultural acceptability may be a challenge.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106759"},"PeriodicalIF":2.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of A. paeoniifolius extracts on bone growth and osteoporosis via inhibiting RANKL-mediated pathway","authors":"Mrinal Sanaye ,&nbsp;Maria Alva ,&nbsp;Tejal Wani ,&nbsp;Arindam Banerjee ,&nbsp;Rajasekaran R","doi":"10.1016/j.jsbmb.2025.106746","DOIUrl":"10.1016/j.jsbmb.2025.106746","url":null,"abstract":"<div><div>Osteoporotic fractures are commonly observed in postmenopausal women. The major risk factor involved is estrogen deficiency. Phytoestrogens, structurally identical to 17-estradiol, have been shown to decrease bone turnover markers, increase bone mineral density, and provide protection against osteoporosis. The present study involves probing the molecular mechanism of <em>Amorphophallus paeoniifolius (</em>AP<em>)</em> rich in phytoestrogens viz kaempferol, rutin, quercetin, and gallic acid, as some therapeutic moieties in the treatment of osteoporosis. The study involves extraction of AP followed by MTT assay for cytotoxicity, and RT-PCR for evaluating the mRNA expression of <em>RANKL</em>, <em>ALP</em>, <em>IL-6</em>, Osteopontin (<em>OPN</em>), and Osteocalcin (<em>OCN</em> <!-->) and western blot analysis of <em>RANKL</em>, along with bone mineralization assay. In the MTT assay, AP extracts showed biocompatibility in both MG-63 and UMR-106, with downregulation of osteoclast differentiation factors <em>RANKL</em>, and <em>IL-6</em> and upregulation of osteoblastic markers <em>OPN</em>, <em>OCN</em> <!-->, and <em>ALP</em> through RT-PCR analysis at 50 μg/ml. In western Blot analysis, decreased protein expression of RANKL indicates reduced bone resorption. A significant increase in Alizarin red dye staining intensity during treatment confirms the progression of calcium deposition, thereby ensuring bone remineralization. The study reveals that AP, promotes osteoblast differentiation, bone re-mineralization, and re-calcification by the downregulation of the <em>RANKL</em>-mediated pathway, suggesting potential therapeutic efficacy for the treatment of post-menopausal osteoporosis.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106746"},"PeriodicalIF":2.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zingerone modulates the circulating steroids hormone levels and testicular steroidogenic markers expression in mice: An in vivo and in silico study","authors":"Miti Jerang ,&nbsp;Guruswami Gurusubramanian ,&nbsp;Ved Prakash Singh ,&nbsp;Vikas Kumar Roy","doi":"10.1016/j.jsbmb.2025.106748","DOIUrl":"10.1016/j.jsbmb.2025.106748","url":null,"abstract":"<div><div>Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a phytochemical with potent anti-inflammatory and antioxidant properties. It has been shown that zingerone protects testis under pathological conditions by its antioxidant and anti-inflammatory effects. However, there is no direct evidence that zingerone specifically affects the testicular steroidogenesis in normal conditions. Therefore, in this study, we have investigated the effects of zingerone on testicular steroidogenesis by using in vivo and silico approaches. The mice were divided into four groups: Control, 10, 25, and 50 mg/kg dosages of zingerone, which were administered orally for 35 days. It was observed that zingerone treatment modulates both circulating hormone levels and the expression of steroidogenic protein markers. Specifically, the higher doses of zingerone resulted in an increase in the circulating estrogen and androstenedione levels, while progesterone, testosterone, and follicle-stimulating hormone levels were reduced. Further, no significant change was observed in the circulating LH level. The higher doses of zingerone resulted in an increased expression and localisation of 3βHSD, CYP19A1, LHR and decreased expression and localisation of StAR, CYP11A1, and 17βHSD protein. Our silico studies showed that the steroidogenic proteins (CYP11A1, 3βHSD, 17βHSD) when double docked with zingerone alongside its native ligands (cholesterol, pregnenolone, androstenedione) showed an increase in the binding affinity. In contrast, StAR, CYP19A1 when double docked with zingerone and its native ligands exhibited a lesser binding affinity compared to when these proteins were single docked with their native ligand and zingerone. In conclusion, in vivo study showed zingerone stimulates androstenedione, estrogen secretion and up-regulates the expression of CYP19A1, LHR and 3βHSD proteins, whereas it down-regulates the expression of StAR, CYP11A1 and 17βHSD proteins and circulating testosterone, progesterone, follicle-stimulating hormone levels. Furthermore, in silico study has also shown the binding affinities of zingerone with the steroidogenic markers. Thus, zingerone has modulatory effects on testicular steroid biosynthesis in normal mice.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"251 ","pages":"Article 106748"},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}