MicroRNAs are a kind of small non-coding single-stranded RNA molecules that negatively regulate the gene expression by binding to imperfect complementary sites in the 3' untranslated region of targeted mRNAs at the post-transcriptional level. Aberrant expressions of some miRNAs like miR-221/222, miR-146a and miR-125b have been found to be significantly associated with androgen-independent progression of prostate cancer. By analyzing the aberrant expressions and regulation mechanisms of miRNAs in cell lines, tissues and peripheral blood samples, we hope to provide a new theoretic base for the clinical diagnosis and treatment of androgen-independent prostate cancer.
Androgens ; pharmacology ; Humans ; Male ; MicroRNAs ; metabolism ; Prostatic Neoplasms ; metabolism

Partial androgen deficiency in aging males can be defined as a clincal condition characterized by a partial deficiency of androgen in blood and/or a decrease genomic sensitivity to testosterone or its active metabolites in target tissues. This state of hypogondism leads to a decline of physical energy, an altered state of well-being, a sexual dysfunction and various metabolic alterations. Testosterone supplement therapy can improve all these symptoms.
Aging ; physiology ; Androgens ; blood ; deficiency ; Humans ; Male ; Testosterone ; pharmacology

Prostate cancer generally relapses into castration resistant prostate cancer (CRPC) after androgen deprivation therapy, which may be associated with androgen metabolism, particularly de novo androgen synthesis apart from the amplification and mutation of androgen receptor and the activation of its signaling pathways. This article focuses on the advances in the studies of the changes in androgen metabolism and de novo androgen synthesis in CRPC as well as their possible mechanisms and clinical significance.
Androgen Antagonists ; pharmacology ; Androgens ; biosynthesis ; metabolism ; Humans ; Male ; Orchiectomy ; Prostate ; metabolism ; Prostatic Neoplasms, Castration-Resistant ; metabolism

Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins (HDL) cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.
Androgens ; adverse effects ; pharmacology ; physiology ; Doping in Sports ; Humans ; Sports ; Weight Lifting

The effects of androgen on lipid and the cardiovascular system are very important. The relationship between androgen and lipoprotein is rather complicated and influenced by many factors. The effects of endogenous androgen on the metabolism of lipoprotein vary with age, environment, nutrition and gender, while the effects of exogenous androgen on lipoprotein vary with different androgen preparations, administration methods and diseases to be treated. Androgen can impact the metabolism of lipoprotein, vascular endothelium, macrophage, vascular smooth muscle, angiotasis, blood coagulation, platelet and so on. The effects of polymorphism of the androgen receptor gene CAG on the cardiovascular system are important and yet somehow controversial and have to be further investigated.
Androgens ; pharmacology ; physiology ; Cardiovascular System ; drug effects ; Female ; Humans ; Lipoproteins ; metabolism ; Male ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; physiology

Androgen has been claimed for so long as a pivotal hormone in regulating male sexual function, acting both at the central and peripheral level. We believe that androgen is indeed the main synchronizer of sexual activity regulating libido and enzymes as nitric oxide synthase (NOS) and phosphodiesterase type 5 ( PDE5) , which are crucial for the erectile process. The main action of androgen is to timely adjust the erectile process as a function manifestation of sexual desire, therefore finalizing erection to sex.
Androgens ; pharmacology ; physiology ; Animals ; Male ; Nitric Oxide Synthase ; metabolism ; Penile Erection ; drug effects ; physiology ; Phosphoric Diester Hydrolases ; metabolism ; Rats

OBJECTIVETo investigate the impact of protein kinase B (Akt2) allele deletion on testicular reproductive function, and to discuss the regulatory effect of Cryptotanshinone on the reproductivity of male mice with Akt2 allele deletion and its molecular mechanism.

METHODSFifteen Akt2 +/+ male mice were randomly divided into Groups A (baseline control, n = 7) and B (stimulation, n = 8), and another 29 Akt2 -/- male mice into C (baseline control, n = 7), D (stimulation, n = 8), E (solvent, n = 7) and F (Cryptotanshinone, n = 7). Groups B and D underwent human chorionic gonadotropin (HCG) stimulation tests at 5 IU / 20 g, while A and C received physiological saline, all for 4 hours; Group F were given gastric lavage of Cryptotanshinone, while E solvent only, at 600 mg/kg twice a day for 8 weeks, both subjected to oral glucose tolerance tests (OGTT) at 2 g/kg before and after the treatment. The body and bilateral testis weights were obtained, the serum testosterone (T) level measured, and the expressions of testicular steroid hormone synthesis and glycometabolism-related genes determined by RT-PCR.

RESULTSOGTT showed that the level of blood glucose was significantly higher in Groups C and D than in A and B ([10.38 +/- 1.42] and [10.96 +/- 1.81] mmol/L vs [7.92 +/- 0.63] and [8.32 +/- 0.44] mmol/L, P < 0.05), but had no significant differences at different time points in E and F (P > 0.05). The testis weight was remarkably higher in Groups C and D than in A and B ([0.17 +/- 0.01] and [0.17 +/- 0.01] g vs [0.15 +/- 0.01] and [0.15 +/- 0.02] g, P < 0.05), but exhibited no obvious difference in E and F, nor were there any significant differences in body weight among different groups (P > 0.05). The serum T level was markedly higher in Group C than in A ([9.08 +/- 1.59] nmol/L vs [6.42 +/- 0.95] nmol/L, P < 0.05), but evidently lower in F than in E ([5.94 +/- 0.49] nmol/L vs [8.18 +/- 1.44] nmol/L, P < 0.05). The baseline expression levels of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA were significantly higher in Group C than in A (P < 0.05). After HCG stimulation, the expressions of Cyp11, Cyp17, 3B-HSD, and Star mRNA were remarkably increased in B and D, but with no obvious difference between the two groups (P > 0.05), while the expressions of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA markedly decreased in F as compared with E (P < 0.05).

CONCLUSIONAkt2 gene deletion may affect glycometabolism and testicular function, and cause abnormal glycometabolism and androgen secretion in male mice, whose molecular mechanism is associated with the elevated expressions of the key glycometabolic molecules and of the key enzymes for androgen synthesis. Cryptotanshinone can reduce the levels of androgens by down-regulating the expressions of the key enzymes for androgen synthesis.

Androgens ; blood ; Animals ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-akt ; genetics ; Sequence Deletion

AIMTo determine whether testosterone is involved in morphine withdrawal syndrome (WS).

METHODSIn order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS.

RESULTSThe severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats.

CONCLUSIONIt can be concluded that testosterone might be effectively involved in morphine WS.

Androgen Antagonists ; pharmacology ; Androgens ; pharmacology ; physiology ; Animals ; Behavior, Animal ; Female ; Flutamide ; pharmacology ; Male ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Narcotics ; pharmacology ; Orchiectomy ; Rats ; Rats, Wistar ; Severity of Illness Index ; Substance Withdrawal Syndrome ; physiopathology ; Testosterone ; pharmacology ; physiology

OBJECTIVETo observe depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-week intervals for the suppression of spermatogenesis in healthy Chinese men.

METHODSAfter screening, 30 healthy volunteers were enrolled and randomly assigned to 3 dosage-groups (n = 10/group): 1000 mg TU (Group A), 1000 mg TU plus 150 mg DMPA (Group B), 1000 mg TU plus 300 mg DMPA (Group C). All dosages were given as intramuscular injections at 8-week intervals. The study consisted of an 8-week control (baseline) period, a 24-week treatment period and a 24-week recovery period.

RESULTSConsistent azoospermia or severe oligozoospermia was achieved and maintained in all the volunteers during the treatment period, except 2 in the mere TU group who experienced a "rebound" in sperm concentrations. An 8-week regimen of TU plus DMPA at both tested combination dosages effectively suppressed spermatogenesis to azoospermia. All volunteers tolerated the injections; no serious adverse effects were reported.

CONCLUSIONThe lower combined dosage is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.

Adult ; Androgens ; pharmacology ; China ; Gonadotropin-Releasing Hormone ; biosynthesis ; Humans ; Hypothalamo-Hypophyseal System ; metabolism ; Male ; Medroxyprogesterone Acetate ; pharmacology ; Prospective Studies ; Sperm Count ; Spermatogenesis ; drug effects ; Testosterone ; analogs & derivatives ; pharmacology

Androgens control a broad range of physiological functions. The androgen receptor (AR), a steroid receptor that mediates the diverse biological actions of androgens, is a ligand inducible transcription factor. Abnormalities in the androgen signaling system result in many disturbances ranging from changes in gender determination and sexual development to psychiatric and emotional disorders. Androgen replacement therapy can improve many clinical conditions including hypogonadism and osteoporosis, but is limited by the lack of efficacious and safe therapeutic agents with easy delivery options. Recent progress in the area of gene regulation by steroid receptors and by selective receptor modulators provides an opportunity to examine if selective androgen receptor modulators (SARMs) could address some of the problems associated with current androgen therapy. Since the composition of the transcriptional initiation complex recruited by liganded AR determines the specificity of gene regulation, synthetic ligands aimed at initiating transcription of tissue and promoter specific genes offers hope for developing better androgen therapy. Establishment of assays that predict synthetic ligand activity is critical for SARM development. Advancement in high throughput compound screening and gene fingerprinting technologies, such as microarrays and proteomics, will facilitate and accelerate identification of effective SARMs.
Androgen Antagonists ; pharmacology ; Androgen Receptor Antagonists ; Androgens ; chemistry ; metabolism ; Chlormadinone Acetate ; analogs & derivatives ; pharmacology ; Humans ; Male ; Receptors, Androgen ; physiology ; Receptors, Cytoplasmic and Nuclear ; physiology ; Testosterone Congeners ; pharmacology