Androgen deficiency impairs erectile function in rats through promotion of corporal fibrosis

The aim of this study was to investigate the underlying mechanism of androgen deficiency inducing corporal fibrosis, thereby causing erectile dysfunction (ED). Forty 12‐week‐old healthy male rats were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 20 rats were castrated followed by testosterone (T) (orally) each day: castration + 10mg/kg T group (Castration + 10T) and castration + 20 mg/kg T group (Castration + 20T). After 8 weeks' treatment, the main outcome measures were the following: serum levels of T; the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP); histologic changes in penile smooth muscle cells; the Smad and non‐Smad pathways; and extracellular matrix (ECM) protein deposition. Castration group showed lower level of T and ratio of ICP/MAP, reduced ratio of penile smooth muscle cells/collagen, increased extracellular matrix protein deposition, and a higher expression of the Smad and non‐Smad pathways. Castration + 10T partially preserved erectile function and histology stabilisation. However, the Castration + 20T group showed significantly better erectile function and molecular changes. Better efficacy could be expected with ART of adequate dose. Androgen deficiency induces corporal fibrosis through activation of the Smad and non‐Smad pathways, and accumulation of ECM proteins.     

Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study

Background

This multicenter, randomized, open-label, active-controlled study evaluated therapeutic equivalence, steady-state pharmacokinetics, and safety of a novel abiraterone acetate fine particle formulation (AAFP) 500 mg plus methylprednisolone vs. the originator AA (OAA) 1000 mg plus prednisone in men with metastatic castrate-resistant prostate cancer (mCRPC). The primary endpoint was a comparison of average of serum testosterone levels on treatment days 9 and 10 between groups.

Afternoon T: testosterone level is higher in red than yellow male polychromatic lizards

Recent work on within-species polymorphism across a broad range of taxa has renewed and considerably increased the attention to this classic evolutionary area, notably in lizard species where colors covary with reproductive strategies. We demonstrate elsewhere that red-headed males beat yellow-headed males in staged contests for females in the Australian painted dragon lizard Ctenophorus pictus. This morph difference in behaviour is linked to what appears to be a convention of red dominance in male-male interactions set very early in ontogeny, long before coloration has developed. In the current note, we investigate the relationship between time of day, which is directly linked to vigilance time in territorial males, and plasma levels of testosterone and corticosterone. We show that red males have higher testosterone levels in late afternoon following a day of territory patrolling and a non-significant trend in plasma corticosterone levels that decline with time of day. In conclusion, there are significant differences in testosterone profile between the two color morphs, providing a potential proximate link to the behavioural differences between them.     

Laterality in syrinx muscle morphology of the Japanese quail (Coturnix japonica)

In the Japanese quail, normally only males crow, but treatment of adult females with testosterone (T) facilitates the behavior. The sternotrachealis muscles are thought to adjust the length of the trachea during inspiration and/or expiration and control rigidity of the cartilages of the vocal organ (syrinx) during phonation. These muscles are heavier in males than females, and T increases their mass in females [Balthazart J, Schumacher M, Otttinger MA. Sexual differences in the japanese quail: Behavior, morphology, and intracellular metabolism of testosterone. Gen Comp Endocrinol 1983; 51:191-207., Schumacher M, Balthazart J. The effects of testosterone and its metabolites on sexual behavior and morphology in male and female Japanese quail. Physiol Behav 1983; 30:335-339.]. To investigate sex differences in morphology and potential effects of T in more detail, we examined several components of male, female, and T-treated female quail syrinx. No group effects were detected on overall tracheal size, size of the tracheal lumen, quantity of cartilage, overall muscle volume, or cross-sectional muscle area. However, the area and estimated volume of the muscles were greater on the right than left, due to increased fiber number. The similarity across groups suggests that if the sternotrachealis muscles are critical for crowing, morphology in females is sufficient, and the sex difference in behavior has another source. In contrast, these muscles may not play as large a role as previously hypothesized. If the increased number of fibers on the right has a functional consequence, it likely reflects one similar in the two sexes, for example a common role in the vocalizations they each produce--the male's crow and the female's cricket call.     

共培养大鼠睾丸体细胞组织工程技术构建雄激素分泌组织

目的：探讨应用组织工程技术体内外构建具有一定形态和睾酮分泌功能组织的可行性。方法：雄性Wister大鼠,无菌切取双侧睾丸,制备去势及移植鼠动物模型。睾丸去包膜,剪碎,胶原酶消化,经差速贴壁或直接混合共培养方法,分别获取睾丸间质细胞（Leydig细胞）和共培养的睾丸多种体细胞,两类细胞分别与可降解生物材料聚羟基乙酸（PGA）纤维复合并进行体外培养,光、电镜观察体外组织形成过程,定期检测培养液内睾酮分泌水平。取体外培养7d细胞-材料复合物,分别移植于去势鼠睾丸鞘膜腔或大网膜内（n=6）,不同时间点取材,通过大体观察、组织学染色和免疫细胞化学方法,检测移植鼠体内雄激素分泌组织的形成过程及血睾酮水平。结果：两类细胞均与PGA具有良好的亲和性,体外可形成具有一定睾酮分泌功能的细胞-材料复合物,体内移植2个月后,两类细胞-材料复合物在大网膜和睾丸鞘膜内均可形成具有一定形态的雄激素分泌组织,再生组织具有良好的血管化。血睾酮检测及统计分析结果表明,移植6周后,单纯Leydig细胞组血睾酮水平为（0．604±0．04）μg/L,共培养细胞组血睾酮水平为（0．854±0．03）μg／L,均明显高于单纯去势鼠血睾酮水平（0．564±0．05）μg/L（P〈0．01）,两组移植鼠相比,共培养细胞移植组血睾酮水平明显高于单纯Leydig细胞移植组（P〈0．01）。结论：以共培养睾丸体细胞作为种子细胞在体内外构建雄激素分泌组织具有可行性,共培养睾丸内体细胞是雄激素分泌组织构建的良好种子细胞。     

男性胃癌患者血清性激素水平的变化

目的探讨性激素在男性胃癌发病中的意义。方法采用放射免疫分析法检测32例男性胃癌患者及30例同年龄男性健康体检者血清中的雌二醇(ESTRADIOL,E2)、睾酮(Testosterone,T)及泌乳素(Prolactin,PRL)水平。结果胃癌组血清E2、T、PRL分别为41.81±5.53pg/ml、813.36±47.57ng/dl、14.35±1.52ng/ml,胃癌组血清E2、T明显低于对照组(P<0.05),而PRL明显高于对照组(P<0.05)。结论男性胃癌的发生可能与性激素代谢失衡有一定的关系。     

Physiological testosterone levels enhance chondrogenic extracellular matrix synthesis by male intervertebral disc cells in vitro,but not by mesenchymal stem cells

Background contextTestosterone (T) is a hormone and regulator involved in the processes of development of the organism (ie, promoting development of bone and muscle mass). Although T effects on the mesenchyme-derived muscle, bone, and adipose tissues are well studied, T effects on intervertebral disc (IVD) have not been reported.PurposeThe aim was to test the following hypothesis: if a physiological concentration of T (～30 nM) can improve in vitro chondrogenesis of human IVD cells and mesenchymal stem cells (MSCs).Study design/settingHuman IVD cells and MSCs were differentiated to chondrogenic lineage on gelatin scaffolds for 4 weeks, in the presence or absence of T.MethodsChondrogenesis was assessed by cell viability, by measuring gene expression with quantitative polymerase chain reaction and extracellular matrix (ECM) accumulation with immunoblotting, immunohistochemical, and biochemical methods.ResultsSupplementation of T to chondrogenic culture did not affect viability. In male IVD cells, T had a beneficial impact on chondrogenesis, particularly in nucleus pulposus cells, demonstrated by an increased expression of aggrecan, collagen type I, and especially collagen type II. Conversely, T had no effects on chondrogenesis of female IVD cells or MSCs from both genders. A gene expression array of transforming growth factor β/bone morphogenetic protein signaling cascade showed that in male IVD cells, T promoted a stable general but nonsignificant increase in gene expression. Furthermore, aromatase inhibitor anastrazole repressed the effect of T on ECM expression by IVD cells. The results suggest that T increased ECM accumulation in male IVD cells in combination with its conversion to estradiol by the enzyme aromatase.ConclusionsWe demonstrated that T effectively enhances in vitro chondrogenesis in male IVD cells, rising the interest in the possible role of sex hormones in IVD degeneration. Nevertheless, T does not affect chondrogenic differentiation of female IVD cells and MSCs from both genders.     

酪氨酸、米非司酮和睾酮对大鼠颗粒细胞凋亡的影响

大多数哺乳类动物的卵巢卵泡在排卵前闭锁，研究表明其发生机制是细胞凋亡。本实验观察了卵巢调控因子酪氨酸、米非司酮和睾酮对大鼠卵巢颗粒细胞凋亡的影响。结果：米非司酮和睾酮促进凋亡，造成ＤＮＡ的片段化反应；而酪氨酸的作用则相反。与对照组相比，米非司酮和睾酮组血清雌二醇含量下降而孕酮含量升高；酪氨酸组血清雌二醇水平升高而孕酮水平下降。米非司酮和睾酮增加闭锁卵泡数，酪氨酸作用则相反。