Testosterone synthesis

In this study, we applied AcmB2, sourced from Sterolibacterium denitrificans, to catalyze the oxidative dehydrogenation of 3-ketolupeol (lupenone), a derivative of lupeol, triterpene obtained from birch bark. This enzymatic Δ1 -dehydrogenation catalyzed by AcmB2 yielded glochidone, a bioactive compound frequently obtained from medicinal plants like Salvia trichoclada and Maytenus boria. Glochidone is known for its broad biological activities, including antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic as well as acetylcholinesterase inhibition...

Letrozole, an aromatase inhibitor preventing estrogen synthesis from testosterone, is used as an adjuvant therapy in estrogen receptor-positive breast cancer patients. However, like other aromatase inhibitors, it induces many side effects, including impaired cognition. Despite its negative effect in humans, results from animal models are inconsistent and suggest that letrozole can either impair or improve cognition. Here, we studied the effects of chronic letrozole treatment on cognitive behavior of adult female BALB/c mice, a relevant animal model for breast cancer studies, to develop an appropriate animal model aimed at testing therapies to mitigate side effects of letrozole...

IMPORTANCE: The adrenal androgen-metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer...

Forest musk deer is the most important animal for natural musk production, and the musk composition changes periodically during musk secretion, accompanied by variation in the com-position of deer-symbiotic bacteria. GC-MS and 16S rRNA sequencing were conducted in this study, the dynamic changes to correlated chemical composition and the microbiota across musk secretion periods (prime musk secretion period, vigorous musk secretion period and late musk secretion period) were investigated by integrating its serum testosterone level in different mating states...

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate...

Per- and poly-fluoroalkyl substances (PFAS) pose a threat to organisms and ecosystems due to their persistent nature. Ecotoxicology endpoints used in regulatory guidelines may not reflect multiple, low-level but persistent stressors. This study examines the biological effects of PFAS on Eastern short-necked turtles in Queensland, Australia. In this study, blood samples were collected and analysed for PFAS, hormone levels, and functional omics endpoints. High levels of PFAS were found in turtles at the impacted site, with PFOS being the dominant constituent...

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1 -/- zebrafish ( Danio rerio ) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1 -/- fish compared to cyp17a1 +/+ male fish, including stearoyl-CoA desaturase ( scd ) and fatty acid synthase ( fasn )...

Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility...

To clarify the causes of sex differences (male < female) in the serum total cholesterol (TCHO) and triglyceride (TG) levels in Meishan pigs, we examined the sex differences in mRNA levels of key hepatic enzymes involved in the biosynthesis/metabolism of cholesterol and TG using real-time RT-PCR. There were no sex differences in mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase and CYP51A1 for cholesterol biosynthesis, or of the rate-limiting enzyme CYP7A1 for bile acid synthesis from cholesterol...

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality...

INTRODUCTION: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. METHODS AND RESULTS: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis...

The worldwide prevalence of Aflatoxin B1 (AFB1 ), which contaminates feedstock and food, is on the rise. AFB1 inhibits testosterone (T) biosynthesis, but the mechanism is not yet clear. By establishing in vivo and in vitro models, this study found the number of Leydig cells (LCs), T content, and the expression of T biosynthesis key enzymes were suppressed after AFB1 treatment. AFB1 exposure also increased reactive oxygen species (ROS) and promoted mitochondrial injury and mitochondrial pathway apoptosis. Moreover, the AMPK signaling pathway was activated, and using an AMPK inhibitor relieved apoptosis and the suppressed T biosynthesis key enzymes of LCs caused by AFB1 through regulating downstream p53 and Nur77...

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured...

Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress...

A unified total synthesis route has been used to prepare 18- and 19-trideuterated testosterone, androstenedione and progesterone. The 18-trideuterated steroid synthetic method starts with the synthesis of 2-(methyl-d3)-1,3-cyclopentanedione from CD3I and 1,3-cyclopentanedione and is subsequently converted into the Hajos-Parrish ketone for synthesis of these trideuterated steroids. The 19-trideuterated steroid synthesis proceeds through non-deuterated Hajos-Parrish ketone with incorporation of the 19-methyl-d3 group from CD3I at a later stage of the same synthetic route...

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown...

PURPOSE: 11β-hydroxylase deficiency (11β-OHD) constitutes a rare form of congenital adrenal hyperplasia (CAH), typically accounting for ~5-8% of CAH cases. Non-classical 11β-OHD is reported even more rarely and frequently results in misdiagnosis or underdiagnosis due to its mild clinical symptoms. METHODS: A clinical, biochemical, radiological, and genetic study was conducted on a 9-year-old girl presenting with mild breast development, axillary hair growth, and advanced bone age...

BACKGROUND: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. OBJECTIVES: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo ...

Haloacetic acids (HAAs) are ubiquitous in drinking water and have been associated with impaired male reproductive health. However, epidemiological evidence exploring the associations between HAA exposure and reproductive hormones among males is scarce. In the current study, the urinary concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the internal exposure markers of HAAs, as well as sex hormones (testosterone [T], progesterone [P], and estradiol [E2 ]) were measured among 449 Chinese men...

PURPOSE: To determine the relationship between serum total testosterone (TT) levels and oxidative stress indices in patients with polycystic ovary syndrome (PCOS), and to investigate the effect of oxidative stress on androgen synthesis and its mechanism in rat ovarian theca-interstitial (T-I) cells. METHODS: Clinical, hormonal, metabolic, and oxidative stress parameters were analyzed in a cross-sectional case-control study including 626 patients with PCOS and 296 controls...