Steroid Synthesis Research Articles

Sex-specific decline in prefrontal cortex mitochondrial bioenergetics in aging baboons correlates with walking speed.

Mitochondria play a crucial role in brain aging due to their involvement in bioenergetics, neuroinflammation and brain steroid synthesis. Mitochondrial dysfunction is linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. Using a novel approach, we assessed mitochondrial bioenergetics from frozen prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6-22.8 years, approximately equivalent to 26.4-91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when activities were normalized for citrate synthase activity, suggesting that the decline in respiration is predominantly driven by changes in the specific activity of individual complexes rather than changes in mitochondrial number. Moreover, when donor sex was used as a covariate, we found that mitochondrial respiration was preserved with age in females, whereas males showed significant loss of ETC activity with age. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity relative to females. Circulating cortisol levels correlated only with complex II-linked respiration in males. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a previously unknown link between aging and bioenergetics across multiple tissues linking frailty and bioenergetic function. This study highlights a potential molecular mechanism for sexual dimorphism in brain resilience and suggests that in males changes in PFC bioenergetics contribute to reduced motor function with age.

Dmrt1 Is Responsible for Androgen-Induced Masculinization in Nile Tilapia.

17α-Methyltestosterone (MT) is a widely used androgen for all-male fish production in aquaculture. However, the molecular mechanism underlying MT-induced masculinization remains unclear. In this study, we aim to identify the key gene responsible for MT-induced masculinization using the Nile tilapia (Oreochromis niloticus) amhy, dmrt1, and gsdf mutants, which exhibit male-to-female sex reversal. Nile tilapia fry from these three mutant lines were treated with 50 μg/g MT from 5 to 30 days after hatching (dah). The results showed that amhy and gsdf mutants, but not dmrt1 mutants, were masculinized by the MT treatment. Gonadal transcriptome analysis revealed that genes involved in steroidogenesis and germ cell development in MT-treated dmrt1 mutants exhibited a similar expression pattern to that of the wild type (WT) XX. In addition, the dmrt1 mutants cannot be masculinized by co-treatment with MT and the aromatase inhibitor fadrozole. The MT treatment completely blocked early steroidogenic enzyme (Star2, Cyp17a2, and Cyp19a1a) expression independent of amhy, gsdf, and dmrt1. A luciferase analysis showed that MT directly suppressed basal and Sf-1-activated cyp19a1a promoter activity through ara and arb in cultured HEK293 cells. Furthermore, MT treatment inhibited germ cell proliferation in amhy and gsdf mutants but not in dmrt1 mutants. Consistently, dmrt1 expression was induced in MT-treated WT XX, -amhy, and -gsdf mutants. Taken together, these results suggest that dmrt1 is indispensable for MT-induced masculinization in Nile tilapia and that MT functions by inhibiting early steroid synthesis and activating dmrt1 to promote testis development.

Design, Synthesis, Anti-TMV Activity, and Structure-Activity Relationships of Seco-pregnane C21 Steroids and Their Derivatives.

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

Engineering of a hydroxysteroid dehydrogenase with simultaneous enhancement in activity and thermostability for efficient biosynthesis of ursodeoxycholic acid.

Hydroxysteroid dehydrogenases have emerged as indispensable tools in the synthesis of steroids, bile acids, and other steroid derivatives for the pharmaceutical and chemical industries. In this study, a novel approach was developed to simultaneously improve the stability and activity of a hydroxysteroid dehydrogenase by combining B-factor analysis and computer-aided prediction. This semi-rational method was demonstrated to be highly effective for enzyme engineering. In addition, NAD kinase was introduced to convert NAD+ to NADP+ for effective coenzyme regeneration in the whole-cell multienzyme-catalyzed system. This strategy reduces the significant economic costs associated with externally supplemented cofactors in NADP-dependent biosynthetic pathways.

CTBP1 links metabolic syndrome to polycystic ovary syndrome through interruption of aromatase and SREBP1

Some patients with polycystic ovarian syndrome (PCOS) suffered from metabolic syndrome (MetS) including dyslipidemia, hyperinsulinism, but the underlying mechanism is unclear. Although C-terminal Binding Protein 1 (CTBP1) is a transcriptional co-repressor frequently involved in hormone secretion disorders and MetS-associated diseases, the role of CTBP1 in PCOS is rarely reported. In the present study, we found that CTBP1 expression was significantly elevated in primary granulosa cells (pGCs) derived from the PCOS with MetS patients and was positively associated with serum triglyceride, but negatively correlated with serum estradiol (E2) or high-density lipoprotein. Mechanistic study suggested that CTBP1 physically bound to the promoter II of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) to inhibit the aromatase gene transcription and expression, resulting in the reduced E2 synthesis. Moreover, CTBP1 interacted with the phosphorylated SREBP1a at S396 in nuclei, leading to the FBXW7-dependent protein degradation, resulting in the reduced lipid droplets formation in pGCs. Therefore, we conclude that CTBP1 in GCs dysregulates the synthesis of steroid hormones and lipids through suppression of aromatase expression and promotion of SREBP1a protein degradation in PCOS patients, which may offer some fresh insights into the potential pathological mechanism for this tough disease.

Anti-Müllerian hormone deficiency leads to two distinct ovarian phenotypes with different alterations of sex hormones in gynogenetic carp

Anti-Müllerian hormone (Amh) plays conserved roles in gonadal development and function in vertebrates. Previous studies have demonstrated that amh deficiency results in severe gonadal hypertrophy in teleost. Here, we report a novel phenotype of gonadal atrophy caused by amh knockout in fish. Firstly, it was found that the amh gene had three alleles and was expressed in the cytoplasm of follicle cells in gynogenetic amphiploid gibel carp (Carassius gibelio). Subsequently, we constructed a mutant line of amh and identified two distinct ovarian abnormalities in gibel carp. Most mutants exhibited hypertrophic ovaries with increased proliferation and decreased differentiation of early germ cells, which is consistent with previously reported findings. Intriguingly, a small number of mutants displayed atrophic ovaries with decreased proliferation and premature differentiation of germ cells, which represents a novel phenotype in fish species. Transcriptome analysis revealed that these two distinct ovaries of amh mutants showed different alterations in the sex hormone biosynthesis pathway, when compared with wild-type ovaries. Furthermore, diverse gonadal sex hormone levels were also detected in these two abnormal ovaries, which were consistent with the transcriptional expressions of corresponding genes in the sex hormone synthesis pathway. These findings identify a novel atrophic ovarian phenotype of amh mutants and confirm the amh function in controlling the balance between proliferation and differentiation of germ cells in fish.

Effects of dietary cholesterol on ovary development and reproductive capacity in Pacific white shrimp broodstock, Litopenaeus vannamei

Cholesterol is an important component of fresh biological baits and essential precursor to synthesize steroid hormones for crustacean. However, the cholesterol demand in Pacific white shrimp broodstock and its roles on ovary development and reproductive capacity are unknown. In the present study, female Pacific white shrimp broodstock (initial weight 51.3 ± 0.5 g) were fed with three diets contained 0.5 %, 1 % or 1.5 % cholesterol for 45 days. The results found that dietary cholesterol levels did not affect survival rate, weight gain, egg-laying number, vitellogenin content and vitellogenin receptor gene expression in the hepatopancreas. However, the hepatosomatic index, gonadosomatic index, egg diameter, vitellogenin level in the ovary and fertilized egg, C22:6n-3 (DHA) level in the fertilized egg, total protein, triglyceride and cholesterol contents were all increased in the 1.0 % and 1.5 % cholesterol groups than those in the 0.5 % cholesterol group. Moreover, compared with the 0.5 % and 1.0 % cholesterol groups, the 1.5 % cholesterol group had significantly higher gonad maturation number, mating rate, estradiol level in the hemolymph, steroid hormones synthesis related genes (HMGCR, StAR, 17βHSD and 1vMFBP) expression in the ovary and hepatopancreas. In conclusion, dietary 1.5 % cholesterol could promote ovary development and reproductive capacity in female Litopenaeus vannamei broodstock by improving nutrients accumulation and steroid hormones synthesis pathway. Our results provide guidance for design of artificial compound feed and healthy development of shrimp broodstock farm.

Identification of candidate genes and pathways involved in the establishment of sexual size dimorphism in the olive flounder (Paralichthys olivaceus) using RNA-seq

Olive flounder (Paralichthys olivaceus) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 (fzd3) and prolactin (prl) in brains/pituitaries, and growth hormone receptor (ghr), estrogen receptor (esr1), insulin-like growth factor binding protein-3 (igfbp3), bone morphogenetic protein 8A-like (bmp8a), leptin receptor (lepr), and lipoprotein lipase-like (lpl) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.

Mouse testicular macrophages can independently produce testosterone and are regulated by Cebpb

BackgroundTesticular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved.ResultsTranscriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis.ConclusionsThis research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.

Effects of Heat Stress-Induced Sex Hormone Dysregulation on Reproduction and Growth in Male Adolescents and Beneficial Foods.

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2-6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Prenatal exposure to environmentally relevant levels of PAHs inhibits spermatogenesis in adult mice and the mechanism involved

Polycyclic aromatic hydrocarbons (PAHs) are a class of contaminants that cannot be banned. Exposure to PAHs has been reported to alter spermatogenesis in mammals, but little is known about prenatal exposure to a mixture of PAHs on the reproductive toxicity of adult offspring. In this study, we investigated the associations between prenatal exposure to environmentally relevant levels of PAHs in mice and testicular dysfunction, including impaired spermatogenesis and steroid hormone dysfunction in male offspring on postnatal day 180. The percentage of testicular apoptotic cells was significantly increased, which was further verified by the up-regulated BAX protein. The expression of Ar and the Leydig cell marker Cyp11a1 was down-regulated, suggesting an impairment in the synthesis of steroid hormones. DNA hypermethylation of the Tnp1 and Sohlh2 promoters suppresses transcriptional expression, consequently altering the sperm production process. This study shows that prenatal exposure to PAHs may induce long-term reproductive toxicity.

VITAMIN B2 AND ITS STATUS IN VEGETARIANS AND VEGANS

The main goal of this review was to briefly highlight the key points of today’s knowledge about the role and metabolism of vitamin B2 as well as to compare its status in vegans, vegetarians, and omnivores according to present data. Biologically active forms of water-soluble vitamin B2 (riboflavin) are represented by flavin mononucleotide (FMN) and flavin adenine diphosphate (FAD), which are coenzymes in the reactions of the electron transport chain and the pyruvate dehydrogenase complex. Riboflavin is also involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones. Riboflavin also participates in the folate cycle. Vitamin B2 is crucial for the metabolism of other vitamins. FMN is necessary for the for-mation of the active form of vitamin B6, while FAD is necessary for the synthesis of niacin. Severe clinical insufficiency of vitamin B2 is not common. Besides insufficient riboflavin consumption, hypothyroidism can also be a cause of vitamin B2 deficiency as thyroxine regulates the conversion of ribo-flavin to its active forms  FMN and FAD. Lack of riboflavin can cause tissue damage; especially of the epithelial, reproductive, and nervous system. The variety of its manifestations is related to the fact that riboflavin deficiency also disrupts the metabolism of vitamins B6, or PP. Similarly, riboflavin deficiency can also disrupt the folate cycle, increasing the level of homocysteine which damages vascular intima and leads to endothelial dysfunction and atherosclerosis as a result. Rapid urinary excretion of riboflavin makes it safe even if taken in a high dose, changing the urine colour into bright-yellow. This safety of riboflavin makes it unharmful to be used as an oral tracer for monitoring compliance in clinical research. Ultra-high doses of ribo-flavin (more than 400 mg/day) can cause diarrhoea or polyuria. The content of vitamin B2 in animal-derived products is higher than in plant-based ones. This also determines its lower intake in vegans and vegetarians compared to omnivores. While there is a shred of evidence that plant-based diets in-crease the production of bioavailable riboflavin by the gut microbiota, this does not appear to be sufficient to completely compensate for the vegetari-ans’/vegans’ reduced dietary intake of vitamin B2, as most of the researches point the fact that vegans and vegetarians are more prone to lack vita-min B2 than omnivores. At the same time, it should be noted that there exists no universally adopted optimal method for assessing the status of vit-amin B2 in the body. Further research and standardization of methods may ease to assess the prevalence and risks of riboflavin deficiency in various dietary groups

Abstract P148: Loss of Ovarian Estrogen Downregulates Renal Steroidogenesis

Hypertension impacts half of US adults and importantly is more prevalent in men than premenopausal women. Sex hormones, particularly estrogen, have been implicated in this sex-difference. Recently we showed renal medullary estrogenic signaling via the G protein-coupled estrogen receptor 1 promotes sodium excretion in female, but not male, Sprague Dawley (SD) rats which implicates estrogen as a possible female-specific natriuretic factor. This led us to question whether the kidney could produce its own steroids, including estrogen, to respond to salt load changes locally. Evidence in cultured COS-7 and fetal kidney cells indicates the expression and activity of steroidogenic enzymes. Recently, we showed the outer medulla of the female SD rat kidney expresses key enzymes and metabolites involved in sex steroid biosynthesis. It is unknown how ovarian estrogen regulates steroidogenesis in the kidney. We hypothesize that ovarian estrogen stimulates the intrarenal capacity to biosynthesize sex steroids. To test this, we measured mRNA expression of several steroidogenic enzymes in the renal outer medulla of gonadally-intact female or ovariectomized SD rats (N=6). Cholesterol is the initial substrate for steroid synthesis. Thus, we first measured HMG-CoA reductase (HMGCR), the key synthesizing enzyme for cholesterol and steroidogenic acute regulatory protein (StAR), which helps commit cholesterol to steroid synthesis. Ovariectomy (OVX) reduced mRNA expression of both when compared to intact females (HMGCR: 63.5 ± 6.2 vs 100.0 ± 10.7 P=0.0169; StAR: 66.6 ± 12.4 vs 100.0 ± 6.4 P=0.0298). Although not significantly different, OVX seemed to reduce the expression of hydroxysteroid 3-β Dehydrogenase, which converts several intermediate steps in androgen and estrogen synthesis, compared to intact females (73.4 ± 13.3 vs 100.0 ± 9.7 P=0.1283). Hydroxysteroid 17-β Dehydrogenase (17β-HSD) 1, which converts estrone to estradiol, was unchanged in OVX compared to intact females (107.6 ± 13.2 vs 100.0 ± 10.1 P=0.6537). OVX reduced expression of 17β-HSD2 (28.34 ± 7.8 vs 100.0 ± 12.85 P=0.0008) and 17β-HSD3 (71.1 ± 7.5 vs 100.0 ± 5.7 P=0.0097) which interconvert androstenedione and testosterone compared to intact females. Combined these data suggest that ovariectomy blunts the intrarenal machinery for steroidogenesis. Additional experiments are required to test whether menopause downregulates renal sex steroid biosynthesis and predisposes postmenopausal women to hypertension.

A multi-omics approach reveals that lotus root polysaccharide iron ameliorates iron deficiency-induced testicular damage by activating PPARγ to promote steroid hormone synthesis

Iron deficiency is a common nutritional issue that seriously affects male reproductive health. Lotus root polysaccharide iron (LRPF), a novel nutritional supplement, may ameliorate the damage caused by iron deficiency, however, the mechanism is unclear. In this study, we comprehensively determined the benefits of LRPF on reproduction in iron-deficient mice by integrating transcriptomics, microbiomics and serum metabolomics. Microbiomics showed that LRPF could restore changes to the intestinal microbiota caused by iron deficiency. Metabolomics results showed that LRPF stabilised steroid hormone and fatty acid metabolism in iron-deficient mice, reduced the content of ethyl chrysanthemumate (EC) and ameliorated the reproductive impairment. The transcriptomic analysis showed that LRPF regulated steroid hormone synthesis and the peroxisome proliferator-activated receptor (PPAR) signalling pathway in iron-deficient mice. In vitro experiments showed that LRPF could promote steroid hormone synthesis in Leydig cells by activating PPARγ. In conclusion, this study highlights the advantage of LRPF to improve testicular development.

The role of endoplasmic reticulum stress in the pathogenesis of oral diseases.

The endoplasmic reticulum (ER) is crucial for protein synthesis, transport, and folding, as well as calcium storage, lipid and steroid synthesis, and carbohydrate metabolism. Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the ER lumen due to increased protein secretion or impaired folding. While the role of ERS in disease pathogenesis has been widely studied, most research has focused on extraoral diseases, leaving the role of ERS in intraoral diseases unclear. This review examines the role of ERS in oral diseases and oral fibrosis pathogenesis. A systematic search of literature through July 2023 was conducted in the MEDLINE database (via PubMed) using specific terms related to ERS, oral diseases, and fibrosis. The findings were summarized in both table and narrative form. Emerging evidence indicates that ERS significantly contributes to the pathogenesis of oral diseases and fibrosis. ERS-induced dysregulation of protein folding and the unfolded protein response can lead to cellular dysfunction and inflammation in oral tissues. Understanding the relationship between ERS and oral disease pathogenesis could offer new therapeutic targets for managing oral health and fibrosis-related complications.

How to manage Cushing's disease after failed primary pituitary surgery.

The first-line treatment for Cushing's disease is transsphenoidal adenomectomy, which can be curative in a significant number of patients. The second-line options in cases of failed primary pituitary surgery include repeat surgery, medical therapy, and radiation. The role for medical therapy has expanded in the last decade, and options include pituitary-targeting drugs, steroid synthesis inhibitors, and glucocorticoid receptor antagonists. Bilateral adrenalectomy is a more aggressive approach, which may be necessary in cases of persistent hypercortisolism despite surgery, medical treatment, or radiation or when rapid normalization of cortisol is needed. We review the available treatment options for Cushing's disease, focusing on the second-line treatment options to consider after failed primary pituitary surgery.

Molecular characterization and expression profiling of 3 beta-hydroxysteroid dehydrogenase and hydroxysteroid 17-beta dehydrogenase in response to HCG stimulation in striped murrel, Channa striata (Bloch, 1793)

Striped murrel (Channa striata) is highly valued in the Indian subcontinent and Southeast Asia for its nutritional and medicinal benefits. However, the limited availability of high-quality seeds of murrel and the asynchronous maturation of brooders, particularly during peak spawning seasons creates problems in aquaculture. Beta-hydroxysteroid dehydrogenases (β-HSDs) are steroidogenic enzymes involved in the biosynthesis of active steroids in gametogenesis and steroidogenesis. This study aimed to clone and characterize the full-length cDNA sequences of two crucial enzymes, 3-beta hydroxysteroid dehydrogenase (Hsd3β) and 17-beta hydroxysteroid dehydrogenase (Hsd17β). It resulted in full-length cDNA sequences for Hsd3β and Hsd17β with 1101bp and 771bp length, respectively, encoding 366 and 256 amino acids. Signal peptide analysis indicated that both proteins are secretory, and hydropathy profiles suggested their hydrophilic nature. Notably, Rossmann-fold NAD(P)(+)-binding domains characteristic of Short-chain dehydrogenases/reductases (SDR) family genes were identified in Hsd3β (between 9-355 aa) and in Hsd17β (between 10-254 aa). Gene expression analyses were performed in testes and ovaries using qPCR at three key stages: preparatory, mature, and 16 h post human chorionic gonadotropin (hCG) injection (16 hpi). Results demonstrated a significant 2-fold upregulation of Hsd17β in mature and 16 hpi testes, while Hsd3β showed a significant 10-fold upregulation in mature testes compared to premature and 16 hpi stages. Ovarian expression of Hsd3β and Hsd17β showed minimal expression upon hCG injection (P < 0.05). These findings contribute to our understanding of Beta-hydroxysteroid dehydrogenases (β-HSDs), providing insights into regulating sex steroid hormone synthesis during the gonadal development of striped murrel.

Influence of estrogen on right ventricular mitochondrial function in pulmonary hypertension

There is a female predominance in pulmonary arterial hypertension (PAH) with a ~4:1 female-to-male ratio. However, female PAH patients exhibit better right ventricular (RV) function and thus better survival than the males. The majority of the current PAH therapies target pulmonary vascular remodeling and/or vasoconstriction in the pulmonary vasculature. However, no therapies directly target the RV, partially because the underlying mechanisms of RV failure in PAH are not fully understood. Since the RV serves as the main determinant of mortality, clarifying the mechanism of RV failure and the associated sex differences in PAH may promote the development of novel therapeutic strategies. Numerous molecular abnormalities have been detected in RV in PAH, particularly due to the suppression of mitochondrial function, including the inhibition of glucose oxidation and a shift to uncoupled aerobic glycolysis (Warburg metabolism) and excessive mitochondrial fission. The mitochondrial suppression is associated with hypocontractility and increased apoptosis in RV cardiomyocytes, and the hyperproliferative, pro-fibrotic, and apoptosis-resistant phenotypes in RV fibroblasts in PAH. Mitochondria also serve as the site for sex steroid synthesis, and in turn, the sex steroids, particularly estradiol (E2), influence the mitochondria both indirectly and directly. It is not well understood how E2 affects mitochondrial function in RV in PAH. Hence, this review focuses on the key mitochondrial genes and proteins that are influenced by PAH, E2, and sex.

Whole transcriptome sequencing revealed the gene regulatory network of hypoxic response in yak Sertoli cells

Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.

Integrative analysis of RNA-seq and Ribo-seq reveals that lncRNA-GRN regulates chicken follicular atresia through miR-103-3p/FBXW7 axis and encoding peptide

Follicular atresia in chickens seriously reduced the egg production and economic benefits of chickens. LncRNA plays a key role in the process of follicular atresia. In this study, RNA-seq and Ribo-seq were performed on normal and atretic follicles of Dahen broilers to screen out lncRNAs that may regulate follicle atresia, and to study the molecular mechanisms of their regulation. GRN granulin precursor (lncGRN, ID: 101748909) was highly expressed in atretic follicles with translational ability. A molecular regulatory network of lncGRN/miR-103-3p/FBXW7 was constructed through bioinformatics analysis and dual luciferase reporting. LncGRN promoted the expression of FBXW7 by adsorption of miR-103-3p, thereby inhibiting the proliferation of chicken granulosa cells (GCs), promoting apoptosis of chicken GCs and inhibiting steroid hormone synthesis thus induced follicular atresia. Meanwhile, we also found a micropeptide named GRN-122aa derived by lncGRN which can promote follicular atresia. In conclusion, our study found that lncGRN promoted follicular atresia through the lncGRN/miR-103-3p/FBXW7 axis and the translation micropeptide GRN-122aa. This study provided new insight into the post-transcriptional regulation mechanism of lncGRN suggesting that lncGRN may act as a potential to regulate chicken follicle development, and provided a theoretical argument for further improving the egg production of chickens through molecular breeding.