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

Humans ; Finasteride/pharmacology* ; Dutasteride/pharmacology* ; 5-alpha Reductase Inhibitors/pharmacology* ; Testosterone/metabolism* ; Hair Follicle/metabolism* ; Transcriptome ; Hair/metabolism*

OBJECTIVETo establish a prostatic hyperplasia model with Beagle canines.

METHODSTwenty-four two-year-old male Beagle canines were divided into treatment and control groups at random and were administrated testosterone propionate (TP) through intramuscular injection two months after castration. Three treatment groups were given 0.8, 2.5 and 7.5 mg/kg TP respectively, and the control was given the same volume of vehicle. Two months later, half of the animals were killed and the serum and prostate were prepared. After the wet weight and volume of prostate were measured, the dihydrotestosterone (DHT) level of serum and prostate were detected with DHT radioimmunoassay (RIA) kit, and paraffine section from canine prostate was stained by the HE methods. Pictures were taken by digital camera under microscope, and all the pictures were analyzed by computer for epithelial cell height and acinar luminal area of prostate with micro image analysis software. The canine prostate volume was measured with ultrasonic diagnosis instrument before castration, at two months after castration and at two months after being given TP.

RESULTSThe ultrasonic results showed that the prostate volumes of all the canines were smaller at two months after castration than before castration (P < 0.05), and after having been administrated TP for two months, and the prostate volumes of all treatment groups were larger than those of the control group (P < 0.01). The wet weight of the prostate of the treatment group was higher than that of the control group (P < 0.05), and both had dose-dependent relationship. The DHT level of serum and prostate of the canines became higher with the increase of TP dose. The results of micro image analysis showed that the acinar luminal area of prostate was enlarged, and the epithelial cell height increased with larger dose of TP.

CONCLUSIONSIt is practicable to establish prostatic hyperplasia model in Beagle canines after two months of TP administration.

Animals ; Dihydrotestosterone ; blood ; Disease Models, Animal ; Dogs ; Male ; Orchiectomy ; Prostatic Hyperplasia ; etiology ; Testosterone Propionate ; pharmacology

AIMTo investigate the effects of testosterone on bone mineral density (BMD), plasma levels of sex hormone and calcium, phosphorus, and parathyroid hormone (PTH).

METHODSThirty 10 week old male rabbits were randomized into sham operated (SH), orchiectomized (ORX) and testosterone undecanoate replacement (TU) group. TU rabbits were injected with testosterone undecanoate in 10 orchiectomized rabbits and the remaining SH and ORX rabbits, vehicle only 20 weeks after initiation of the experiment, bone mineral density was measured with dual-energy X-ray bone densitometer. Blood was collected for determination of serum levels of total testosterone, estradiol, calcium, magnesium, phosphorus and alkaline phosphatase (AKP).

RESULTSThe serum levels of total testosterone and femoral neck BMD decreased, serum levels of calcium, magnesium and AKP increased significantly in ORX rabbits, testosterone improved femoral neck BMD and decreased serum levels of calcium, magnesium and AKP significantly in TU rabbits.

CONCLUSIONThe results of the present study indicate that ORX decrease serum testosterone and BMD, exogenous testosterone treatment can prevent osteoporosis in ORX rabbits.

Animals ; Bone Density ; drug effects ; Calcium ; blood ; Male ; Orchiectomy ; Phosphorus ; blood ; Rabbits ; Testosterone ; pharmacology

OBJECTIVE: Although the protective effects of Momordica charantia L. (MC) extract on chemical-induced testicular damage have been studied, the preventive effects of MC extract on functional proteins in the epididymis under chronic stress have never been reported. This study investigated the protective effects of MC fruit extract on protein secretion, especially tyrosine-phosphorylated proteins, in the epididymis of rats exposed to chronic unpredictable stress (CUS). METHODS: Total phenolic compounds (TPC), total flavonoid compounds (TFC) and antioxidant capacities of MC extract were measured. Adult male rats were divided into 4 groups: control group, CUS group, and 2 groups of CUS that received different doses of MC extract (40 or 80 mg/kg). In treated groups, rats were given MC daily, followed by induction of CUS (1 stressor was randomly applied from a battery of 9 potential stressors) for 60 consecutive days. Plasma corticosterone and testosterone levels were analyzed after the end of experiment. Expressions of heat-shock protein 70 (HSP-70) and tyrosine-phosphorylated proteins present in the fluid of the head and tail of the epididymis were quantified using Western blot. RESULTS: MC extract contained TPC of (19.005 ± 0.270) mg gallic acid equivalents and TFC of (0.306 ± 0.012) mg catechin equivalents per gram, and had 2,2-diphenyl-1-picrylhydrazyl antioxidant capacity of (4.985 ± 0.086) mg trolox equivalents per gram, radical 50% inhibitory concentration of (2.011 ± 0.008) mg/mL and ferric reducing antioxidant power of (23.697 ± 0.819) µmol Fe(II) per gram. Testosterone level in the epididymis was significantly increased, while the corticosterone level was significantly improved in groups treated with MC extract, compared to the CUS animals. Particularly, an 80 mg/kg dose of MC extract prevented the impairments of HSP-70 and tyrosine-phosphorylated protein expressions in the luminal fluid of the epididymis of CUS rats. CONCLUSION MC fruit extract had antioxidant activities and improved the functional proteins secreted from the head and tail of the epididymis. It is possible to develop the MC fruit extract as a male fertility supplement for enhancing functional sperm maturation in stressed men.
Male ; Rats ; Animals ; Antioxidants/pharmacology* ; Tyrosine/metabolism* ; Plant Extracts/therapeutic use* ; Corticosterone ; Seeds ; Testosterone ; Fruit/metabolism*

OBJECTIVESTo confirm whether regeneration of prostate lobe indeed takes place on surgical lobectomy and if so, to what extent. Other issues studied are 1. whether the lobe regenerated is similar morphologically to that developing normally from neonatal origin to adulthood, and 2. the consequences of partial lobectomy on the contralateral lobe and the influence of sex steroid hormones on the regeneration process.

METHODSThe effect of surgical removal of one of the ventral prostate lobes on the size of the contralateral lobe has been studied at various time intervals after lobectomy.

RESULTSThe surgically extirpated ventral prostate lobe in rats regenerates attaining plateau size at 8-16 weeks post lobectomy. The regenerated lobe, however, remains significantly smaller than the original size. In early phase of post lobectomy (at 2 weeks) the contralateral lobe was significantly hypertrophied. It reverts to normal size on regeneration of the extirpated lobe with time. Orchiectomy carried out at the time of lobectomy caused a drastic reduction in the size of the remaining lobe, which was prevented by exogenous treatment with androgens. In animals receiving treatment with estrogens, the remaining lobe was partially but not fully atrophied. However, estrogens did not support the regeneration of the surgically removed lobe, which requires androgens.

CONCLUSIONSThese studies demonstrate that surgical removal of one of the ventral prostate lobe leads to a process of regeneration. However, the regenerated lobe does not attain the normal size.

Animals ; Estradiol ; pharmacology ; Male ; Orchiectomy ; Prostate ; drug effects ; physiology ; Prostatectomy ; Prostatic Hyperplasia ; etiology ; Rats ; Rats, Wistar ; Regeneration ; Testosterone ; pharmacology

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

Male antifertility drugs can induce contraception by interfering with spermatogenesis progression. Their action mechanism is correlated with the apoptosis of spermatogenic cells. This paper summarizes recent researches on the mechanism of male antifertility-drugs, including testosterone, gossypol, tamoxifen and triptolide, reviews their regulating effect on cell apoptosis and the expression of the key genes and proteins involved, and explores the significance of further researches on male antifertility drugs and cell apoptosis.
Apoptosis ; drug effects ; genetics ; Caspases ; genetics ; metabolism ; Contraceptive Agents, Male ; pharmacology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Gene Expression ; drug effects ; Gossypol ; pharmacology ; Humans ; Male ; Phenanthrenes ; pharmacology ; Tamoxifen ; pharmacology ; Testosterone ; 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

OBJECTIVETo investigate the effects of phytoestrogens (daidzein and genistein) on the testosterone production of rat Leydig cells and the possible mechanisms.

METHODSPrimary Leydig cells were obtained from 3-month old male SD rats using discontinuous Percoll density gradient centrifugation. The effects of phytoestrogens at various concentrations were evaluated by ELISA, with hCG as the positive control. The mRNA expression of P450 side-chain cleavage enzyme (P450scc) was analyzed by semi-quantitative RT-PCR.

RESULTSGenistein at 0.1 micromol/L obviously promoted the secretion of testosterone and upregulated the mRNA level of P450scc. At a higher concentration of 5 micromol/L, however, both daidzein and genistein significantly inhibited the testosterone production of Leydig cells (P > 0.05).

CONCLUSIONGenistein can promote the testosterone production of Leydig cells at a low concentration (0.1 micromol/L), but both daidzein and genistein can inhibit it at a higher concentration ( >5 micromol/L).

Animals ; Cells, Cultured ; Genistein ; pharmacology ; Isoflavones ; pharmacology ; Leydig Cells ; drug effects ; secretion ; Male ; Phytoestrogens ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; biosynthesis