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Hormones and Behavior May 2008Androgens act on the CNS to affect motor function through interaction with a widespread distribution of intracellular androgen receptors (AR). This review highlights our... (Review)
Review
Androgens act on the CNS to affect motor function through interaction with a widespread distribution of intracellular androgen receptors (AR). This review highlights our work on androgens and process outgrowth in motoneurons, both in vitro and in vivo. The actions of androgens on motoneurons involve the generation of novel neuronal interactions that are mediated by the induction of androgen-dependent neurite or axonal outgrowth. Here, we summarize the experimental evidence for the androgenic regulation of the extension and regeneration of motoneuron neurites in vitro using cultured immortalized motoneurons, and axons in vivo using the hamster facial nerve crush paradigm. We place particular emphasis on the relevance of these effects to SBMA and peripheral nerve injuries.
Topics: Androgens; Animals; Axons; Cells, Cultured; Cricetinae; Facial Nerve; Humans; In Vitro Techniques; Motor Neurons; Nerve Regeneration; Neurites; Receptors, Androgen
PubMed: 18387610
DOI: 10.1016/j.yhbeh.2008.01.014 -
Molecular and Cellular Endocrinology Mar 2018Doping with anabolic-androgenic steroids (AAS) is common among both male and female athletes and is a growing public health problem. Review of historical data of... (Review)
Review
Doping with anabolic-androgenic steroids (AAS) is common among both male and female athletes and is a growing public health problem. Review of historical data of systematic state-sponsored doping programs implemented by the German Democratic Republic in elite female athletes and from clinical trials of testosterone administration in non-athlete women suggests that AAS have ergogenic effects in women. The use of AAS in female athletes has been associated with adverse effects that include acne, hirsutism, deepening of the voice and menstrual disturbances; life-threatening adverse effects such as cardiac arrhythmias and sudden death have also been reported. Therefore, detection of AAS abuse in female athletes is important to ensure fairness in competition; at the same time, the athletes should be educated regarding the adverse consequences of AAS use. Although administration of exogenous androgens have been associated with ergogenic effects, it remains unclear whether endogenous hyperandrogenism seen in some medical conditions such as disorders of sexual development (DSD), congenital adrenal hyperplasia and polycystic ovary syndrome, confers any competitive advantage. Well-designed studies are needed to determine the effects of endogenous hyperandrogenism on athletic performance in female athletes.
Topics: Anabolic Agents; Androgens; Athletes; Athletic Performance; Female; Humans; Performance-Enhancing Substances; Steroids
PubMed: 28711608
DOI: 10.1016/j.mce.2017.07.010 -
European Journal of Pharmaceutical... Nov 2023Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic... (Meta-Analysis)
Meta-Analysis
Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic ovary syndrome (PCOS). However, unclear risk-benefit profiles jeopardize their appropriate clinical applications. This study aimed to quantitatively evaluate the effects of the aforementioned medications and to compare their risk-benefit profiles. Randomized controlled trials published until 14th March 2022 were searched in PubMed and Embase. A model-based meta-analysis was developed to examine the time-effect profiles of each medication. The maximal percentage change of the effect (E) and time to achieve half of E (T) were estimated. Primary outcomes included menstruation, hirsutism score, free androgen index (FAI), body mass index (BMI), insulin sensitivity, and lipid profiles. Overall, 200 studies (9,685 patients and 385 arms) were identified for modeling. OCs performed exceptionally well in improving menstruation (E: 149%; T: 7.44 weeks), hirsutism score (E: 66.2%; T: 26.2 weeks), and FAI (E: 75.7%; T: 0.51 weeks). However, OCs elevated the triglyceride (TG) level (E: 12.6%; T:1.19 weeks). After 12-week OC treatment, the TG level of approximately 30% of patients, whose baselines were normal, exceeded the reference limit. This suggested that OC-induced dyslipidemia should be routinely monitored. The maximal BMI-lowering effect of metformin was similar to that of placebo (E: 3.80%); however, metformin had a shorter T (6.67 weeks versus 12.9 weeks). Further, active lifestyle intervention plus placebo significantly decreased BMI (E: 8.78%). Adding metformin to active lifestyle intervention accelerated the BMI-lowering effect within 24 weeks, whereas with the extension of this addition beyond 24 weeks, BMI did not reduce further, which indicated that benefits were limited from this prolonged addition. AAs were less potent in reducing hirsutism score (E: 40.2% versus 66.2%) and FAI (E: 34.5% versus 75.7%) compared to OCs. OC plus metformin combined OC-derived androgen-suppressing effects and metformin-derived insulin-sensitizing effects, and partially relieved the OC-induced TG increase (E: 9.76%). Baseline dependency was found in most clinical responses, implying that pharmacotherapies tailored based on baselines achieved more clinical improvements. This study presents new quantitative evidence on pharmacotherapies for PCOS. Currently, long-term risk-benefit profiles and emerging therapies are inadequately reported and require more further research.
Topics: Humans; Female; Polycystic Ovary Syndrome; Contraceptives, Oral; Androgen Antagonists; Insulin; Hirsutism; Androgens; Metformin; Hypoglycemic Agents
PubMed: 37666459
DOI: 10.1016/j.ejps.2023.106577 -
The Journal of Clinical Endocrinology... Jun 2021
Topics: Anabolic Agents; Androgens; Fertility; Humans; Male; Steroids
PubMed: 33861859
DOI: 10.1210/clinem/dgab236 -
Hematology. American Society of... Dec 2017Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure... (Review)
Review
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.
Topics: Androgens; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Danazol; Female; Genetic Diseases, Inborn; Genetic Therapy; Humans; Leucine; Oxymetholone; Quercetin; Stem Cell Transplantation; Syndrome; Virilism
PubMed: 29222242
DOI: 10.1182/asheducation-2017.1.96 -
Psychoneuroendocrinology Apr 2018Developmental plasticity is a widespread property of living organisms, but different individuals in the same species can vary greatly in how susceptible they are to... (Review)
Review
Developmental plasticity is a widespread property of living organisms, but different individuals in the same species can vary greatly in how susceptible they are to environmental influences. In humans, research has sought to link variation in plasticity to physiological traits such as stress reactivity, exposure to prenatal stress-related hormones such as cortisol, and specific genes involved in major neurobiological pathways. However, the determinants of individual differences in plasticity are still poorly understood. Here we present the novel hypothesis that, in both sexes, higher exposure to androgens during prenatal and early postnatal life should lead to increased plasticity in traits that display greater male variability (i.e., a majority of physical and behavioral traits). First, we review evidence of greater phenotypic variation and higher susceptibility to environmental factors in males; we then consider evolutionary models that explain greater male variability and plasticity as a result of sexual selection. These empirical and theoretical strands converge on the hypothesis that androgens may promote developmental plasticity, at least for traits that show greater male variability. We discuss a number of potential mechanisms that may mediate this effect (including upregulation of neural plasticity), and address the question of whether androgen-induced plasticity is likely to be adaptive or maladaptive. We conclude by offering suggestions for future studies in this area, and considering some research designs that could be used to empirically test our hypothesis.
Topics: Adaptation, Physiological; Androgens; Animals; Biological Evolution; Female; Humans; Individuality; Male; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Sex Factors; Sexual Behavior
PubMed: 29500952
DOI: 10.1016/j.psyneuen.2018.02.025 -
Physiological Research 2011Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most... (Review)
Review
Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.
Topics: Adipose Tissue; Alopecia; Androgens; Animals; Body Composition; Cardiovascular Diseases; Cholestenone 5 alpha-Reductase; Dihydrotestosterone; Humans; Male; Mice; Obesity; Prostatic Hyperplasia; Rats; Receptors, Androgen; Testosterone
PubMed: 21114370
DOI: 10.33549/physiolres.932080 -
Science Advances Apr 2019Biological receptors distinguish and bind steroid sex hormones, e.g., androgen-, progestogen-, and estrogen-type hormones, with high selectivity. To date, artificial...
Biological receptors distinguish and bind steroid sex hormones, e.g., androgen-, progestogen-, and estrogen-type hormones, with high selectivity. To date, artificial molecular receptors have been unable to discriminate between these classes of biosubstrates. Here, we report that an artificial polyaromatic receptor preferentially binds a single molecule of androgenic hormones, known as "male" hormones (indicated with ), over progestogens and estrogens, known as "female" hormones (indicated with ), in water. Competitive experiments established the binding selectivity of the synthetic receptor for various sex hormones to be testosterone () > androsterone () >> progesterone () > β-estradiol () > pregnenolone () > estriol (). These bindings are driven by the hydrophobic effect, and the observed selectivity arises from multiple CH-π contacts and hydrogen-bonding interactions in the semirigid polyaromatic cavity. Furthermore, micromolar fluorescence detection of androgen was demonstrated using the receptor containing a fluorescent dye in water.
Topics: Androgens; Female; Gonadal Steroid Hormones; Humans; Magnetic Resonance Spectroscopy; Male; Models, Molecular; Molecular Conformation; Molecular Structure; Protein Binding; Receptors, Androgen; Receptors, Aryl Hydrocarbon; Receptors, Steroid; Structure-Activity Relationship
PubMed: 31016239
DOI: 10.1126/sciadv.aav3179 -
European Journal of Medical Research Jun 2022Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to...
BACKGROUND
Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations.
METHODS
Male SD rats aged 3-4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD.
RESULTS
Compared with the control group, the MVD decreased significantly in the castration group (P < 0.05). When the exogenous E concentration was constant, in general, the MVD of rats in all the groups increased with increasing exogenous DHT concentration. Compared with the castration group, the MVD increased significantly in the E0.05 + DHT0.015 mg/kg, E0.05 + DHT0.05 mg/kg, E0.05 + DHT0.15 mg/kg, E0.05 + DHT0.5 mg/kg, and E0.05 + DHT1.5 mg/kg groups (P < 0.05). In addition, when the exogenous DHT concentration was constant, the MVD increased with increasing exogenous E concentration in all the groups. Among them, compared with the control and castration groups, the MVD increased significantly in the DHT0.15 + E0.015 mg/kg, DHT0.15 + E0.15 mg/kg, and DHT0.15 + E0.5 mg/kg groups (P < 0.05).
CONCLUSIONS
Androgens play an important role in the regulation of prostatic MVD in SD rats, and a decrease in DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with increasing DHT concentration. In addition, prostatic MVD can be increased gradually with increasing oestrogen concentration.
Topics: Androgens; Animals; Dihydrotestosterone; Estrogens; Male; Microvascular Density; Prostate; Rats; Rats, Sprague-Dawley
PubMed: 35672771
DOI: 10.1186/s40001-022-00719-7 -
Endocrine Sep 2023The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving...
PURPOSE
The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments.
METHODS
Eight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2-6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses.
RESULTS
Ostarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm vs. 1.18 ± 0.04 g/cm in Orx); other bone parameters remained unaffected. Testosteron Prophylaxis positively influenced cortical density in femur (1.24 ± 0.05 g/cm vs. 1.18 ± 0.04 g/cm in Orx); Test. Therapy did not change any bony parameters.
CONCLUSION
Ostarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Receptors, Androgen; Bone Density; Osteoporosis; Androgens; Testosterone; Androgen Antagonists; Orchiectomy
PubMed: 37378829
DOI: 10.1007/s12020-023-03422-7