ABSTRACT
Gravity in space can have a negative impact on the reproductive system. Given that the reproductive system is one of vitamin D's objectives, this study will use a simulated microgravity model to evaluate its impact on the rat reproductive system.Twenty-two male Wistar rats were allocated into four groups at random. Under microgravity circumstances, the rats were housed in both special and standard cages. Each group was then separated into two subgroups, one of which received vitamin D3 and the other did not. Blood was drawn twice to determine blood levels of vitamin D3, LH, FSH, and testosterone. Rat testes were isolated for histological analysis, as well as a piece of epididymis for sperm count and morphological examination.Microgravity had a detrimental effect on testicular tissue, resulting in lower serum levels of LH and testosterone (p-value < 0.001). Spermatogenesis was largely inhibited under microgravity. During microgravity conditions, however, vitamin D3 had a good effect on testicular structure, and the total number of sperm. Simulated microgravity affects the male reproductive system, compromising testicular morphology, sperm parameters, and hormonal balance. However, this study shows that vitamin D3 supplementation can act as a preventative strategy, minimizing the negative consequences of microgravity. The beneficial effect of vitamin D3 on testicular health and sperm quality implies that it may be useful in protecting male reproductive function in space-related situations.
Subject(s)
Cholecalciferol , Rats, Wistar , Testis , Testosterone , Weightlessness Simulation , Animals , Male , Cholecalciferol/pharmacology , Cholecalciferol/administration & dosage , Testis/drug effects , Testosterone/blood , Rats , Spermatogenesis/drug effects , Spermatogenesis/physiology , Sperm Count , Luteinizing Hormone/blood , Spermatozoa/drug effects , Follicle Stimulating Hormone/bloodABSTRACT
Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.
Subject(s)
5-alpha Reductase Inhibitors , Prostatic Hyperplasia , Animals , Humans , Male , 5-alpha Reductase Inhibitors/therapeutic use , Cholestenone 5 alpha-Reductase , Dihydrotestosterone , Prostatic Hyperplasia/drug therapy , TestosteroneABSTRACT
Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our in vitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.
Subject(s)
Glomerulonephritis , Plant Extracts , Testosterone , Male , Animals , Mice , Leydig Cells , Curcuma , Hydrocortisone , Yang DeficiencyABSTRACT
With aging, men develop testosterone-deficiency syndrome (TDS). The development is closely associated with age-related mitochondrial dysfunction of Leydig cell and oxidative stress-induced reactive oxygen species (ROS). Testosterone-replacement therapy (TRT) is used to improve the symptoms of TDS. However, due to its various side effects, research on functional ingredients derived from natural products that do not have side effects is urgently needed. In this study, using the mitochondrial dysfunction TM3 (mouse Leydig) cells, in which testosterone biosynthesis is reduced by H2O2, we evaluated the effects of elderberry extract and monosaccharide-amino acid (fructose-leucine; FL) on mRNA and protein levels related to steroidogenesis-related enzymes steroidogenic acute regulatory protein (StAR), cytochrome P450 11A1(CYP11A1, cytochrome P450 17A1(CYP17A1), cytochrome P450 19A1(CYP19A1, aromatase), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and 17ß-hydroxysteroid dehydrogenase(17ß-HSD). We analyzed elderberry extract and extract-derived FL for changes in ROS scavenging activity and testosterone secretion. Elderberry extract and FL significantly reduced H2O2-induced intracellular ROS levels, improved testosterone secretion, and increased the mRNA and protein expression levels of steroidogenesis-related enzymes (StAR, 3b-HSD, 17b-HSD, CYP11A1, CYp17A1). However, the conversion of testosterone to estradiol was inhibited by elderberry extract and extract-derived FL, which reduced the mRNA and protein expression of CYP19A1. In conclusion, elderberry extract and FL are predicted to have value as novel functional ingredients that may contribute to the prevention of TDS by ameliorating reduced steroidogenesis.
Subject(s)
Hydrogen Peroxide , Leydig Cells , Plant Extracts , Testosterone , Animals , Leydig Cells/metabolism , Leydig Cells/drug effects , Mice , Hydrogen Peroxide/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Male , Cell Line , Amino Acids/metabolism , Monosaccharides , Sambucus/chemistry , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Phosphoproteins/metabolism , Phosphoproteins/geneticsABSTRACT
Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.
Subject(s)
Disease Models, Animal , Gastrointestinal Microbiome , Insulin Resistance , Moxibustion , Polycystic Ovary Syndrome , Rats, Sprague-Dawley , Animals , Polycystic Ovary Syndrome/therapy , Polycystic Ovary Syndrome/metabolism , Female , Moxibustion/methods , Rats , Dehydroepiandrosterone/metabolism , Blood Glucose/metabolism , Insulin/blood , Insulin/metabolism , Metformin/pharmacology , Testosterone/blood , Ovary/metabolism , Ovary/microbiologyABSTRACT
Cumulus cells (CCs) synthesize estrogens that are essential for follicular development. However, the effects of androgen on estrogen production in buffalo CCs remain unknown. In the present study, the impacts of testosterone on estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes were investigated. The results showed that testosterone supplementation improved both the expression levels of estrogen synthesis-related genes (CYP11A1, CYP19A1, and 17ß-HSD) and the secretion levels of estradiol in buffalo CCs surrounding in vitro-matured oocytes. Furthermore, testosterone treatment enhanced the sensitivity of buffalo CCs surrounding in vitro-matured oocytes to follicle-stimulating hormone (FSH). This study indicated that testosterone supplementation promoted the estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes mainly through strengthening the responsiveness of CCs to FSH. The present study serves as a foundation of acquiring high-quality recipient oocytes for buffalo somatic cell nuclear transfer.
Subject(s)
Buffaloes , Testosterone , Female , Animals , Testosterone/pharmacology , Testosterone/metabolism , Cumulus Cells , Oocytes , Follicle Stimulating Hormone/pharmacology , Follicle Stimulating Hormone/metabolism , Dietary Supplements , Estrogens/pharmacology , Estrogens/metabolismABSTRACT
INTRODUCTION: The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature. OBJECTIVE: In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM). METHODS: This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone." RESULTS: The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density. CONCLUSION: There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.
Subject(s)
Hematologic Neoplasms , Hypogonadism , Humans , Hypogonadism/complications , Hypogonadism/etiology , Male , Hematologic Neoplasms/complications , Testosterone/blood , Testosterone/therapeutic useABSTRACT
PURPOSE OF REVIEW: Highlight the importance of exploring nutritional interventions that could be applied as alternative or supplementary therapeutic strategies to enhance men's fertility. RECENT FINDINGS: Lifestyle choices have prompted extensive discussions regarding its implications and applications as a complementary therapy. The growing concern over the decline in sperm quality underscores the urgency of investigating these alternative interventions. Calorie restriction (CR) has emerged as a promising strategy to improve male fertility. The efficacy of CR depends on factors like age, ethnicity and genetics. Clinical studies, such as CALERIE, have shown an improvement in serum testosterone level and sexual drive in men with or without obesity. Additionally, CR has been shown to positively impact sperm count and motility; however, its effects on sperm morphology and DNA fragmentation remain less clear, and the literature has shown discrepancies, mainly due to the nature of technically dependent assessment tools. The review advocates a personalized approach to CR, considering individual health profiles to maximize its benefits. It underscores the need for routine, accessible diagnostic techniques in male reproductive health. It suggests that future research should focus on personalized dietary interventions to improve male fertility and overall well-being in individuals with or without obesity and unravel CR's immediate and lasting effects on semen parameters in men without obesity.
Subject(s)
Caloric Restriction , Fertility , Infertility, Male , Obesity , Humans , Male , Caloric Restriction/methods , Spermatozoa , Testosterone/blood , Sperm Count , Sperm Motility , Semen AnalysisABSTRACT
OBJECTIVE: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older. DESIGN: 2 × 2 factorial design randomized controlled trial, follow up of 12 months. METHODS: Hypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement. RESULTS: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo. CONCLUSION: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.
Subject(s)
Accidental Falls , Hypogonadism , Testosterone , Vitamin D , Humans , Accidental Falls/prevention & control , Male , Testosterone/blood , Aged , Vitamin D/blood , Vitamin D/administration & dosage , Hypogonadism/drug therapy , Aged, 80 and over , Frailty/prevention & control , Frail ElderlyABSTRACT
Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250â¯mgâ¯kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250â¯mgâ¯kg-1 were challenged for the stress by immobilization (SIMB), for 6â¯h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).
Subject(s)
Aphrodisiacs , Infertility, Male , Pterocarpans , Rats , Male , Animals , Humans , Aphrodisiacs/pharmacology , Rats, Wistar , Semen Analysis , Pilot Projects , Molecular Docking Simulation , Pterocarpans/pharmacology , Plant Extracts/pharmacology , Plant Extracts/metabolism , Semen , Testis , Oxidative Stress , Infertility, Male/drug therapy , Infertility, Male/etiology , Infertility, Male/metabolism , Testosterone , Fructose/metabolismABSTRACT
Allium Cepa Linn. (Onions) has extensively been used in traditional medicine, is one of the important Allium species regularly used in our daily diet, and has been the source of robust phenolic compounds. The current study is intended to evaluate the fecundity-enhancing effect of A. Cepa on the reproductive performance of two successive generations of rats; F0 and F1. A. Cepa extract was initially tested for in vitro antioxidant assay via DPPH and ROS, followed by in vivo toxicity testing. In the fecundity assessment, eighteen pairs of male and female rats (n = 36, 1:1, F0 generation) were divided into three groups and dosed with 75mg/kg and 150 mg/kg daily of A. Cepa extract and saline respectively, up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Various parameters like Hematological, Hormonal (FSH, LH, Testosterone, estradiol), antioxidant markers (SOD, Glutathione peroxidase) and lipid profile of F0 and F1 generations were assessed with evaluation of histopathology of male and female organs. Ethanolic extract of A. Cepa showed the greatest antioxidant potential in DPPH and ROS methods. The continued exposure of the F0 and F1 generations to A. Cepa extract did not affect body weight, fertility index, litter size, and survival index. However, semen pH, sperm motility, sperm count, sperm viability, and semen volume were significantly improved in both generations. We have found pronounced fecundity outcomes in both genders of F0 and F1 generations with A. Cepa 150mg/kg/day extract as compared to control. Results showed that A. Cepa significantly increased (P < 0.05) hemoglobin, follicular stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone and glutathione peroxidase activities, while total lipid, LDL, and cholesterol were significantly decreased (P < 0.05) in both generations. Histology of both generations of animals reveals enhanced spermatogenesis and enhanced folliculogenesis with improved architecture. Altogether, the present results suggest that A. Cepa extract improved fecundity in both male and female rats by improving hormonal activities and oxidative stress.
Subject(s)
Antioxidants , Onions , Rats , Male , Female , Animals , Reactive Oxygen Species/pharmacology , Antioxidants/pharmacology , Sperm Motility , Seeds , Reproduction , Fertility , Body Weight , Testosterone , Luteinizing Hormone/pharmacology , Follicle Stimulating Hormone/pharmacology , Glutathione Peroxidase , Lipids/pharmacologyABSTRACT
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. METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350 mW, 808 nM, 2 min/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells. RESULTS: We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7-day PBMT (808 nm, 350 mW/cm2 , 42 J/cm2 ). Furthermore, PBMT significantly increased cerebral blood flow (CBF) and the expression of vascular-associated proteins, while inhibiting vascular permeability and reducing endothelial cell apoptosis. This ultimately mitigated behavioral deficits in PT stroke rats. Notably, treatment with the androgen receptor antagonist flutamide reversed the beneficial effects of PBMT. Cellular experiments confirmed that PBMT inhibited cell apoptosis and increased vascular-associated protein expression in brain endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD). However, these effects were inhibited by flutamide. Moreover, mechanistic studies revealed that PBMT-induced testosterone synthesis in bEnd.3 cells was partly mediated by 17ß-hydroxysteroid dehydrogenase 5 (17ß-HSD5). CONCLUSIONS: Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases.
Subject(s)
Low-Level Light Therapy , Stroke , Humans , Male , Rats , Mice , Animals , Testosterone/metabolism , Androgens/metabolism , Receptors, Androgen/metabolism , Endothelial Cells/metabolism , Flutamide/pharmacology , Flutamide/therapeutic use , Flutamide/metabolism , Stroke/therapyABSTRACT
BACKGROUND: Vitamin D (Vit D) deficiency has been linked to symptoms of polycystic ovary syndrome (PCOS), yet little is known about Vit D supplementation as a treatment for sexual dysfunction (SDy) in women with PCOS. AIM: To explore the implications of serum total 25-hydroxyvitamin D (25[OH]D) and bioavailable 25[OH]D (bio-25[OH]D) status and replacement on women with PCOS and SDy. METHODS: Reproductive-age women with PCOS who were not desiring fertility were eligible provided that they also had SDy, as assessed by the Female Sexual Function Index (FSFI), and were without severe depression, as evaluated by the Beck Depression Inventory II (BDI-II). Participants were given the recommended dietary allowance of Vit D (600 IU daily) plus hormonal contraception (HC; cyclic ethinyl estradiol/drospirenone) or no HC for 6 months. Comparisons between groups were analyzed by chi-square test and t-test, and Pearson's correlation coefficient analyzed correlations between FSFI with demographics, BDI-II, androgen levels, and total and bio-25[OH]D. OUTCOMES: The outcomes included SDy (FSFI <26.55), total and serum bio-25[OH]D levels, and total and free testosterone. RESULTS: A total of 42 women without severe depression completed the FSFI, with 28 (66.7%) having SDy. All FSFI domains, including arousal, lubrication, orgasm, and pain, were significantly lower as compared with women without SDy, with no associations with respect to demographics, total and free testosterone, or total and bio-25[OH]D. Vit D replacement was initiated with HC (n = 18) or no HC (n = 10), and for those completing the study, FSFI improved (score >26.55) in 61% (11/18) regardless of the treatment group. A time-treatment effect showed a significant change for the domain of orgasm, suggesting that HC had more of an impact than Vit D replacement. Improvement in sexual function as a dichotomous variable was not associated with age, body mass index, other demographics, total and free testosterone, total and bio-25[OH]D, or HC use. CLINICAL IMPLICATIONS: Due to the prevalence of SDy in women with PCOS, efficacious treatment options are necessary. STRENGTHS AND LIMITATIONS: This study is the first to analyze the effect of Vit D supplementation on SDy in women with PCOS. Limitations included the small number of participants who completed the study, thus limiting meaningful conclusions and generalizability. CONCLUSION: Vit D status was not associated with SDy and BDI-II. While HC may have played a role, standard Vit D supplementation could not account for the noted improvement in FSFI in women with PCOS.
Subject(s)
Polycystic Ovary Syndrome , Vitamin D/analogs & derivatives , Female , Humans , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Pilot Projects , Vitamin D/therapeutic use , Testosterone , Dietary SupplementsABSTRACT
The involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flutamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5-alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypothalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female rats.
Subject(s)
Androgens , Receptors, Androgen , Rats , Animals , Male , Female , Orexins/metabolism , Androgens/pharmacology , Androgens/metabolism , Rats, Wistar , Agouti-Related Protein/genetics , Receptors, Androgen/metabolism , Body Weight/physiology , Hypothalamus/metabolism , Pro-Opiomelanocortin/genetics , RNA, Messenger/metabolism , Testosterone/pharmacology , Oxidoreductases/metabolismABSTRACT
OBJECTIVES: To explore delayed puberty in cerebral palsy (CP) and to test the acceptability of an interventional puberty induction algorithm. METHODS: A two phase cohort study in children and adolescents diagnosed with CP who have delayed puberty. Phase 1: Retrospective review of clinical records and interviews with patients who have been treated with sex-steroids and Phase 2: Prospective interventional trial of pubertal induction with a proposed algorithm of transdermal testosterone (males) or oestrogen (females). Phase 1 examined experiences with sex-steroid treatment. Phase 2 collected data on height adjusted bone mineral density (BMAD), fractures, adverse effects, mobility and quality of life over two years during the induction. RESULTS: Phase 1, treatment was well tolerated in 11/20 treated with sex-steroids; phase 2, using the proposed induction algorithm, 7/10 treated reached Tanner stage 3 by nine months. One participant reached Tanner stage 5 in 24 months. Mean change in BMAD Z-scores was +0.27â¯% (SD 0.002) in those who could be scanned by dual-energy X-ray absorptiometry (DXA). CONCLUSIONS: Delayed puberty may be diagnosed late. Treatment was beneficial and well tolerated, suggesting all patients with severe pubertal delay or arrest should be considered for sex hormone supplementation.
Subject(s)
Cerebral Palsy , Puberty, Delayed , Adolescent , Child , Female , Humans , Male , Absorptiometry, Photon , Bone Density , Cohort Studies , Gonadal Steroid Hormones , Pilot Projects , Prospective Studies , Puberty , Quality of Life , TestosteroneABSTRACT
Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.
Subject(s)
Meditation , Mindfulness , Male , Humans , Meditation/psychology , Hydrocortisone , Testosterone , Mindfulness/methods , Stress, Psychological/therapy , Stress, Psychological/psychologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sobolifera (CS) has been traditionally utilized as an ethnic remedy for various health conditions, including chronic kidney diseases, anti-fatigue interventions, and management of chronic inflammation. Notably, CS is recognized for its substantial content of bioactive compounds, among which nucleosides prominently feature as constituents with diverse therapeutic advantages. AIM OF THE STUDY: This study aims to investigate the effects of CS on testosterone secretion in Leydig cells and explore the underlying mechanism. MATERIALS AND METHODS: Leydig cells were isolated from rat testes to establish a primary rat Leydig cells model. Cell proliferation and testosterone secretion were assessed via the methyl-piperidino-pyrazole (MTT) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Samples earmarked for RNA sequencing (RNA-Seq) analysis facilitated the identification of significantly differentially expressed genes (DEGs), and we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and enrichment analyses. The veracity of our findings was validated through quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: The results showed that CS and guanosine could promote Leydig cell proliferation and bolster testosterone secretion. Our integrative analysis of metabolomics and transcriptomics has unveiled the potential mechanisms governing testosterone synthesis. Specifically, metabolomics has illuminated striking correlations within cholesterol metabolism, and bile secretion. Concurrently, transcriptomics has underscored the pivotal roles played by the cyclic adenosine monophosphate (cAMP) signaling pathway and steroid hormone biosynthesis. Furthermore, our investigation has demonstrated CS's aptitude in elevating the expression of proteins and genes. Notably, our findings have elucidated that these effects can be mitigated by protein kinase A (PKA) and adenylate cyclase (AC) specific inhibitors. CONCLUSION: This study delineates the cAMP-PKA pathways as plausible mechanisms underpinning the testosterone-enhancing properties of CS, with guanosine emerging as a fundamental bioactive constituent.
Subject(s)
Hypocreales , Leydig Cells , Testosterone , Male , Rats , Animals , Testosterone/metabolism , Multiomics , Cyclic AMP/metabolism , Guanosine/metabolism , Guanosine/pharmacologyABSTRACT
BACKGROUND AND AIM: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. MATERIALS AND METHODS: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). RESULTS: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. CONCLUSION: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.
Subject(s)
Methotrexate , Selenium , Male , Mice , Animals , Methotrexate/adverse effects , Selenium/pharmacology , Caspase 3/metabolism , bcl-2-Associated X Protein/metabolism , Tumor Suppressor Protein p53 , Testosterone , Luteinizing Hormone/metabolism , Malondialdehyde/metabolism , Follicle Stimulating HormoneABSTRACT
Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.