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Molecules (Basel, Switzerland) Jul 2019As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has... (Review)
Review
As a result of the findings of scientists working on the biosynthesis and metabolism of steroids in the plant and animal kingdoms over the past five decades, it has become apparent that those compounds that naturally occur in animals can also be found as natural constituents of plants and vice versa, i.e., they have essentially the same fate in the majority of living organisms. This review summarizes the current state of knowledge on the occurrence of animal steroid hormones in the plant kingdom, particularly focusing on progesterone, testosterone, androstadienedione (boldione), androstenedione, and estrogens.
Topics: Androstadienes; Androstenedione; Animals; Biosynthetic Pathways; Estrogens; Phytosterols; Plants; Progesterone; Steroids; Testosterone
PubMed: 31315257
DOI: 10.3390/molecules24142585 -
International Journal of Molecular... Nov 2021A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal...
A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine () placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrations, increased circulatory testosterone and androstenedione concentrations, and tended to reduce the weight of the fetus ( < 0.1). Moreover, the gene expression of was increased, and the expression of androgen receptor was decreased in the D120 chorioallantois (CA) of letrozole-treated mares in comparison to that of the control mares. We also found that at D120, the number of vessels tended to decrease in the CAs with letrozole treatment ( = 0.07). In addition, expression of a subset of angiogenic genes, such as , , and , were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of and and increases the angiogenic activity of equine endothelial cells in vitro. Our results from the estrogen-suppressed group demonstrated an impaired placental vascular network, suggesting an estrogen-dependent vasculogenesis in the equine CA during the first trimester.
Topics: Androstenedione; Angiopoietin-1; Animals; Aromatase; Estrogens; Female; Gene Expression Regulation, Developmental; Horses; Letrozole; Maternal-Fetal Relations; Neovascularization, Physiologic; Placenta; Pregnancy; Pregnancy Trimester, First; Receptors, Androgen; Steroid 17-alpha-Hydroxylase; Testosterone; Vascular Endothelial Growth Factor A
PubMed: 34829994
DOI: 10.3390/ijms222212116 -
The Journal of Clinical Endocrinology... Nov 2023Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions...
CONTEXT
Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions of sex steroids are poorly understood. Vascular calcification parallels the development of atherosclerosis, but is increasingly recognized as a diversified, highly regulated process, which itself may have pathophysiological importance for clinical cardiovascular events.
OBJECTIVE
To investigate the association between serum sex steroids and coronary artery calcification (CAC) in elderly men.
METHODS
We used gas chromatography tandem mass spectrometry to analyze a comprehensive sex steroid profile, including levels of dehydroepiandrosterone (DHEA), androstenedione, estrone, testosterone, estradiol, and dihydrotestosterone, in men from the population-based AGES-Reykjavik study (n = 1287, mean 76 years). Further, sex hormone-binding globulin (SHBG) was assayed and bioavailable hormone levels calculated. CAC score was determined by computed tomography. The main outcome measures were cross-sectional associations between dehydroepiandrosterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and quintiles of CAC.
RESULTS
Serum levels of DHEA, androstenedione, testosterone, dihydrotestosterone, and bioavailable testosterone showed significant inverse associations with CAC, while estrone, estradiol, bioavailable estradiol, and SHBG did not. DHEA, testosterone, and bioavailable testosterone remained associated with CAC after adjustment for traditional cardiovascular risk factors. In addition, our results support partially independent associations between adrenal-derived DHEA and testes-derived testosterone and CAC.
CONCLUSION
Serum levels of DHEA and testosterone are inversely associated with CAC in elderly men, partially independently from each other. These results raise the question whether androgens from both the adrenals and the testes may contribute to male cardiovascular health.
Topics: Aged; Humans; Male; Androstenedione; Coronary Artery Disease; Dehydroepiandrosterone; Dihydrotestosterone; Estradiol; Estrone; Sex Hormone-Binding Globulin; Testosterone; Vascular Calcification
PubMed: 37391895
DOI: 10.1210/clinem/dgad351 -
Frontiers in Endocrinology 2022To investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS.
OBJECTIVE
To investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS.
METHODS
We conducted a cross-sectional study of 166 women with PCOS and 139 age-matched control women at Peking University Third Hospital (Beijing, China) from March 2016 to December 2021. All participants underwent bioimpedance rate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, body composition parameters were assessed, based on the methods used in a previous study. Homeostasis model assessment-insulin resistance (HOMA-IR) and other indices calculated from fasting glucose and insulin were used to measure insulin resistance. The hormonal profiles [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), total testosterone (T), and androstenedione (A2)] were assessed by using biochemical methods. Two subgroup analyses were conducted according to waist-to-hip ratio (WHR; < 0.85, non-central obesity and ≥ 0.85, central obesity) and body fat percentage (BFP; < 35% for lean and ≥35% for obesity). The indices above were analyzed using a two-sided t-test or Wilcoxon rank sum test. Linear regression was used to investigate the effects of body composition on metabolism and sex hormones in the PCOS and control groups.
RESULTS
Compared to women without PCOS, women with PCOS and central obesity (=0.021), PCOS and noncentral obesity (<0.001), PCOS and high BFP (<0.001), and PCOS and low BFP (<0.001) had more severe glucose metabolism evaluated with HOMA-IR. Women with PCOS experienced greater insulin sensitivity impairment than did the normal population for every equal increase in BFP. LH, LH/FSH, total testosterone, and androstenedione were significantly higher in patients with PCOS than in healthy controls, regardless of WHR and BFP stratification. However, negative correlations existed between body fat indices (i.e., BFP and body mass index) and hormone indices (i.e., LH and androstenedione) in the PCOS group, but were absent in the control group.
CONCLUSIONS
Obese and non-obese women with PCOS have more severe insulin resistance and sex-hormone disorders than women without PCOS. The effect of body fat on sex-hormone disorders is only exist in women with PCOS. These findings suggested that PCOS clinical guidelines should be more specific to body fat.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/, Registration No. NCT04264832.
Topics: Humans; Female; Insulin Resistance; Polycystic Ovary Syndrome; Androstenedione; Cross-Sectional Studies; Luteinizing Hormone; Obesity; Follicle Stimulating Hormone; Testosterone; Gonadal Steroid Hormones; Body Composition; Blood Glucose
PubMed: 36699018
DOI: 10.3389/fendo.2022.1085656 -
Molecules (Basel, Switzerland) May 2022Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl... (Review)
Review
Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry's search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on "process improvement" techniques and on possible modifications of the "microorganism" involved in biosynthesis (64 and 62 documents, respectively). The most-reported "process improvement" technique is "chemical addition" (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the "microorganism" category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: sp. (basonym: sp.) (40%) and (known previously as ) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.
Topics: Androgens; Androstenedione; Biotransformation; Mycobacteriaceae; Phytosterols; Steroids
PubMed: 35630641
DOI: 10.3390/molecules27103164 -
Gynecological Endocrinology : the... Dec 2023To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to...
OBJECTIVE
To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS.
MATERIALS AND METHODS
This is a prospective case control study, 550 women recruited (aged 20-40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient.
RESULTS
The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS.
CONCLUSION
The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Androgens; Anti-Mullerian Hormone; Androstenedione; Case-Control Studies; East Asian People; Testosterone; Peptide Hormones
PubMed: 37141919
DOI: 10.1080/09513590.2023.2206927 -
IScience Jan 2023The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we...
The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome ( < 5 × 10). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites.
PubMed: 36660475
DOI: 10.1016/j.isci.2022.105839 -
Frontiers in Endocrinology 2023Although 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis, it is not clear whether sex hormones mediate this casual association. We aimed to explore how...
BACKGROUND
Although 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis, it is not clear whether sex hormones mediate this casual association. We aimed to explore how sex hormones affect the association between 25(OH)D and osteoporosis to provide meaningful insights on the underlying mechanisms from a genetic perspective.
METHODS
Genetic variations in 25(OH)D, total testosterone (TT), androstenedione (A4), estradiol (E2), and testosterone/17β-estradiol (T/E2) were determined through summary statistics. Taking osteoporosis as the outcome (FinnGen biobank, 332,020 samples), we conducted a Mendelian randomization (MR) analysis to establish the association between 25(OH)D and these sex hormones. The two-step MR analysis quantified the mediatory effects of sex hormones on osteoporosis. The results were further verified by pleiotropy and heterogeneity analyses.
RESULTS
MR results showed that 25(OH)D (OR= 1.27, = 0.04) and TT (OR= 1.25, = 0.04) had a causal effect on osteoporosis. No significant associations were observed between the other sex hormones (A4, E2, and T/E2) and osteoporosis (>0.05). Sensitivity analysis (>0.05) confirmed the robustness of the MR results. The two-step MR analysis provided evidence that the mediatory effect of TT was 0.014 (the percentage of TT mediation was 5.91%). Moreover, the direct effect of 25(OH)D on osteoporosis was 0.221. A4, E2, and T/E2 were not considered as potential mediators of the role of 25(OH)D as a risk factor for OP.
CONCLUSION
This study, through MR analysis, showed that TT mediates the causal effect of 25(OH)D on osteoporosis. Interventions targeting TT, therefore, have the potential to substantially reduce the burden of osteoporosis attributable to high 25(OH)D.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D; Vitamins; Gonadal Steroid Hormones; Osteoporosis; Testosterone; Estradiol
PubMed: 37082118
DOI: 10.3389/fendo.2023.1159241 -
Journal of Personalized Medicine Feb 2023The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of... (Review)
Review
The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of androgens. There are five different androgens produced in women: dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT). The most potent hormones are T and DHT, the latter being mainly produced from T in peripheral tissues, including endometrium. Although they are considered to exert antiproliferative effects in many settings and the expression of their receptors is more often associated with a good prognosis in EC, it is still unknown in which specific settings androgens have carcinogenic or protective effects in EC.
PubMed: 36836575
DOI: 10.3390/jpm13020341 -
Frontiers in Endocrinology 2022Leydig cells (Lc) reside in the interstitial compartment of the testis and are the target of Luteinising hormone (LH) for Testosterone (T) production, thus critically... (Review)
Review
Leydig cells (Lc) reside in the interstitial compartment of the testis and are the target of Luteinising hormone (LH) for Testosterone (T) production, thus critically regulates male fertility. Classical histological studies have identified two morphologically different populations of Lc during testicular development [fetal (FLc) and adult (ALc)]. Recent progress in cell/organ culture, genome-wide analysis, genetically manipulated mouse models, lineage tracing, and single-cell RNA-seq experiments have revealed the diverse cellular origins with differential transcriptomic and distinct steroidogenic outputs of these populations. FLc originates from both coelomic epithelium and notch-active Nestin-positive perivascular cells located at the gonad-mesonephros borders, and get specified as Nr5a1 (previously known as Ad4BP/SF-1) expressing cells by embryonic age (E) 12.5 days in fetal mouse testes. These cells produce androstenedione (precursor of T, due to lack of HSD17β3 enzyme) and play critical a role in initial virilization and patterning of the male external genitalia. However, in neonatal testis, FLc undergoes massive regression/dedifferentiation and gradually gets replaced by T-producing ALc. Very recent studies suggest a small fraction (5-20%) of FLc still persists in adult testis. Both Nestin-positive perivascular cells and FLc are considered to be the progenitor populations for ALc. This minireview article summarizes the current understanding of Lc development in fetal and adult testes highlighting their common or diverse cellular (progenitor/stem) origins with respective functional significance in both rodents and primates. (227 words).
Topics: Mice; Animals; Male; Testis; Leydig Cells; Nestin; Cell Differentiation; Testosterone; Primates
PubMed: 36686449
DOI: 10.3389/fendo.2022.1086276