A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy

Introduction:Prostate-specific antigen (PSA) kinetic patterns during neoadjuvant androgen deprivation therapy have been shown to predict unfavorable long-term outcomes.Objective:To investigate the effect of testosterone escape (TE) on these kinetic patterns, as this had not been previously reported.Methods:There were 50 consecutive prostate cancer patients who received 6 months of triptorelin prior to definitive radiotherapy (RT). Testosterone and PSA levels were measured at baseline and every 6 weeks. Clinical factors were tested for their ability to predict for TE and unfavorable PSA kinetic patterns. The effects of TE, at both 1.7 and 0.7 nmol/L levels, were analyzed.Results:TE occurred in at least one reading for 14% and 34% of the patients at the 1.7 and 0.7 nmol/L levels, respectively. No baseline factors predicted TE. The median PSA halving time was 25 days and the median pre-RT PSA level was 0.55 ng/mL. The only factor significantly associated with a higher pre-RT PSA level was a higher baseline PSA level. The only factor that significantly predicted a longer PSA halving time was TE at the 1.7 nmol/L level.Conclusions:TE and higher baseline PSA levels may adversely affect PSA kinetics and other outcomes for patients undergoing neoadjuvant hormone therapy prior to radiotherapy. Studies investigating the tailoring of neoadjuvant therapy by extending the duration in those patients with a higher baseline PSA level or by the addition of anti-androgens in those demonstrating TE, should be considered.     

用体外器官培养方法研究EDCs对新生小鼠睾丸的影响

目的 通过已建立的小鼠睾丸体外培养系统,研究四种内分泌干扰物（Endocrine Disrupting Chemicals,EDCs）对男性内分泌系统的影响。 方法 将新生小鼠的睾丸组织在体外环境中培养24h,而后在培养基中分别加入浓度为0.1μM, 1μM, 10μM and 100μM的四种（DEHP、MEHP、NP、p, p’-DDE）内分泌干扰物并培养72h,同时设置对照组;培养结束后进行组织学观察,测定冻存培养基中睾酮和抑制素βB (INH-βB)的分泌水平,同时测定细胞色素P450侧链裂解酶(P450Scc)、3β-羟基类固醇脱氢酶(3β-HSD)、细胞色素P45017α-羟化酶(P450C17)和波形蛋白（vimentin）的基因表达情况。 结果 所有剂量组中睾酮的分泌水平均发生改变;P450Scc、3β-HSD、P450C17和INH-βB蛋白质的表达及mRNA水平均受到四种内分泌干扰物的影响（P<0.05）;DEHP和MEHP降低了波形蛋白的mRNA水平（P<0.05）,而NP和p, p’-DDE对波形蛋白没有显著影响（P>0.05）。 结论 本研究建立的体外培养新生小鼠睾丸模型中,所选的四种已知EDCs改变了两种睾丸激素水平,三种类固醇合成酶以及与支持细胞功能相关的波形蛋白的表达。     

阿狄森病患者外周血白细胞性激素受体的改变及意义

应用放射配体结合法检测１６例阿狄森病患者外周血白细胞雌激素受体（ＥＲ）和雄激素受体（ＡＲ），同时用放射免疫分析检测血浆雌二醇（Ｅ２）和睾酮（Ｔ）水平，结果如下：１）阿狄森病患者血浆Ｅ２高于对照组，但无统计学意义，血浆Ｔ无明显改变，Ｅ２／Ｔ比值明显高于对照组（Ｐ〈０．０５）；２）阿狄森病患者白细胞ＥＲ明显高于对照组（Ｐ〈０．０１），ＡＲ轻度降低（Ｐ〉０．０５），ＥＲ／ＡＲ比值明显高于对照组（Ｐ〈０．     

前列腺特异性抗原、前列腺体积与睾酮水平的随龄变化及相关分析

目的:探讨50岁以上男性随增龄血清前列腺特异性抗原(PSA)、前列腺体积与激素变化的规律及相关性。方法:以524名50岁以上男性为研究对象,超声检测仪测前列腺体积,ELISA技术检测血清PSA含量,放射免疫分析法检测血清睾酮、促黄体生成激素(LH)含量。结果:(1)血清PSA含量随增龄增高和前列腺体积随增龄而增大;(2)血清睾酮(T)含量随增龄下降,血清LH含量则随增龄而增高;(3)血清PSA和LH含量与前列腺体积呈显著的正相关;(4)血清睾酮含量与前列腺体积呈负相关(r=-0.45,P＜0.01)。结论:血清PSA含量随增龄增高与前列腺的组织学变化有关,而睾酮水平的下降是前列腺异常增生的重要原因之一。     

Reinforcing aspects of androgens

Are androgens reinforcing? Androgenic-anabolic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, often with negative long-term health consequences. As a result, in 1991, testosterone was declared a controlled substance. Recently, Brower [K.J. Brower, Anabolic steroid abuse and dependence. Curr. Psychiatry Rep. 4 (2002) 377-387.] proposed a two-stage model of AAS dependence. Users initiate steroid use for their anabolic effects on muscle growth. With continued exposure, dependence on the psychoactive effects of AAS develops. However, it is difficult in humans to separate direct psychoactive effects of AAS from the user's psychological dependence on the anabolic effects of AAS. Thus, studies in laboratory animals are useful to explore androgen reinforcement. Testosterone induces a conditioned place preference in rats and mice, and is voluntarily consumed through oral, intravenous, and intracerebroventricular self-administration in hamsters. Active, gonad-intact male and female hamsters will deliver 1 microg/microl testosterone into the lateral ventricles. Indeed, some individuals self-administer testosterone intracerebroventricularly to the point of death. Male rats develop a conditioned place preference to testosterone injections into the nucleus accumbens, an effect blocked by dopamine receptor antagonists. These data suggest that androgen reinforcement is mediated by the brain. Moreover, testosterone appears to act through the mesolimbic dopamine system, a common substrate for drugs of abuse. Nonetheless, androgen reinforcement is not comparable to that of cocaine or heroin. Instead, testosterone resembles other mild reinforcers, such as caffeine, nicotine, or benzodiazepines. The potential for androgen addiction remains to be determined.     

The effect of the ovarian cycle on the sexual behaviour of the common marmoset (Callithrix jacchus)

The sexual behaviour of 7 pairs of marmosets was observed during 30 minute tests for 44-68 days and blood samples were collected from females for measurement of plasma progesterone, testosterone and oestrone. Copulations occurred throughout the ovarian cycle of 24-30 days. Females used a "tongue-flicking" display both as an invitational behaviour (proceptive tongue-flicks) and during copulation (receptive tongue-flicks) most frequently during the peri-ovulatory period. Frequencies of proceptivity were correlated positively with high mean levels of testosterone and oestrone during the cycle and with a short follicular phase. Males showed significant increases in tongue-flicks, mounts and ejaculations during the peri-ovulatory phase, together with a shortened post-ejaculatory interval and increased duration of penile erection after ejaculation. A retrospective analysis showed that these changes in the males' behaviour occurred only during tests where females were proceptive and not during other tests in the peri-ovulatory period. Females refused significantly more of the males' mounting attempts during the luteal phase and a corresponding reduction in mount frequency occurred at this time. Grooming, scent-marking, olfactory inspections and some other behaviours did not alter significantly in either sex during the ovarian cycle.     

Monitoring exercise stress by changes in metabolic and hormonal responses over a 24-h period

Summary Metabolic and endocrine responses of 14 subjects of varying levels of fitness to an intensive anaerobic interval training session were assessed before exercise and at 2 h, 4 h, 8 h and 24 h postexercise. The endocrine response of the same subjects to a control day, where they were required not to exercise, was also assessed and compared with the values obtained on the interval training day. Uric acid, urea, and creatine phosphokinase concentrations still remained elevated above pre-exercise values 24 h postexercise. Lactate, creatinine, testosterone and cortisol concentrations were significantly elevated above pre-exercise values immediately postexercise but these had reversed by 2 h postexercise. Over the remainder of the recovery period testosterone concentrations remained significantly lower than values measured at similar times on the control day. This was shown to be due directly to a change in testosterone as sex hormone binding globulin concentration remained constant throughout the recovery period. The data indicate that when comparisons of data were made to control (rest) days, imbalances in homeostasis, due to intensive training, are not totally reversed within the next 24-h. The data also demonstrate that the parameters measured undergo the same variations in subjects with a wide range of physical fitness, indicating that these parameters could be used to monitor exercise stress and recovery in athletes of a wide range of abilities. The more acute responses to exercise could be mistaken for overtraining if insufficient recovery time were not permitted between the final exercise session and taking blood samples, further emphasising the need to be able to recognise the difference between the fatigue associated with acute exercise and a state of chronic fatigue that may result from too little regeneration time within the training programme.     

Effects of high doses of testosterone propionate and testosterone enanthate on rat seminiferous tubules — a stereological and cytological study

The effects of exogenous testosterone on various testicular variables has become of increasing significance because of its potential use in male contraception. For this reason, high doses of two testosterone esters [testosterone propionate (TP) and testosterone enanthate (TE)] were used in a study of their influence on the morphology, length and curvature of the seminiferous tubules of the rat testis, and on cytological smears of the seminiferous tubules epithelium. TP was given for 14 days (3 mg/100 g body weight, i. m.) to assess the acute effects of testosterone on the seminiferous tubules. TE was administered for 60 days (in the same manner as TP) to study possible chronic effects on the rat testis. After TP and TE treatment the seminiferous tubule epithelium showed disorganization and desquamation of spermatogenic cells. In the TP-treated testes the tubules lined with Sertoli cells only were observed. The values for the length and curvature of seminiferous tubules of the TP- and TE-treated rats were significantly reduced (p<0.001). All these changes were observed earlier in the TP-treated than in the TE-treated animals. In cytological smears of the testis of the TP- and TE-treated rats an increase of vacuoles and residual bodies in Sertoli cell cytoplasm was noted. In addition, a reduction of spermatogenic cells, particularly sperms, was manifest in the smears after treatment. Large groups of Sertoli cells were seen in the smears from these testes.The study was supported by a Grant for Scientific Research No. 3-01-041 from the Ministry of Science, Technology and Informatics of the Republic of Croatia     

睾酮对低氧小鼠红细胞比容和血清促红细胞生成素的影响

为了观察性激素对红细胞生成的作用,应用低压舱(0.42atm,22h/d)分别给小鼠注射人重组促红细胞生成素(rhEPO)、睾酮、皮质醇,检测红细胞比容(Hct)和血清促红细胞生成素(sEPO)的变化。结果表明:低氧6d后,各组sEPO均显著升高(P<0.05);注射rhEPO或睾酮组的Hct显著增加(P<0.05);注射rhEPO或睾酮组的Hct显著增加(P<0.05),而注射皮质醇组Hct改变不显著(P>0.05)。     

阉割和睾酮替代对大鼠应激免疫抑制蛋白的影响

目的 :研究阉割和睾酮替代对束缚应激模型大鼠血清中应激免疫抑制蛋白的影响。方法 :成年雄性SD大鼠随机分为正常对照组、假手术组、阉割组、阉割后睾酮替代组。每组 10～ 12只。以上各组随机抽出一半给予束缚应激 ,另一半作为不应激对照。观察各组大鼠血清对ConA诱导的淋巴细胞转化的作用 ,作为反映血清中应激免疫抑制蛋白含量的指标。在离体实验中观察不同浓度的睾酮对淋巴细胞转化的直接作用。结果 :阉割可促进应激大鼠血清中应激免疫抑制蛋白的产生 ,睾酮替代可对抗这一作用。结论 :睾酮可在一定范围内对抗应激免疫抑制蛋白的产生。