Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization

This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.     

雄激素源性脱发

雄激素源性脱发是由雄性激素引起，为进行性的头发密度减少，其包括男性型脱发及女性弥漫性脱发，曾被强调与皮脂溢出有关。Hamilton和Kuster研究分别证实了雄激素源性脱发是一种雄性激素依赖的多基因遗传性脱发，为治疗男性脱发提供了依据。针对DHT的增高、受体的存在，应用5α还原酶的抑制剂、毛发移植取得了一定的效果。通过本文的阐述，与大家共同探讨。     

Inhibitory effects of Serenoa repens on the kinetic of pig prostatic microsomal 5α-reductase activity

The pathogenesis of benign prostatic hyperplasia is linked to the accumulation of dihydrotestosterone (DHT), the active form of testosterone (T), in prostatic tissue. We have defined characteristics of 5α-reductase enzyme which catalyzes the conversion of T into DHT in prostatic microsomes of growing pigs. Peaks for the 5α-reductase activity were found at pH 5.5 and 8.0, which indicates the presence of both type 1 and type 2 isozymes. Kinetic parameters of porcine 5α-reductase in the presence of Serenoa repens extracts revealed uncompetitive, noncompetitive, and mixed types of inhibitions. Our results show the inhibitory action of S. repens on prostate porcine microsomal 5α-reductase activity.     

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH

The detection of low doses of recombinant growth hormone is a challenge in antidoping testing. Future testing may lead toward the longitudinal monitoring of IGF‐I and P‐III‐NP in an endocrine module. Additional biomarkers, for example vitamin D binding protein, alpha‐HS‐glycoprotein, fibronectin 1, and decorin have been identified in different omics studies. This was a longitudinal study of the usefulness of these putative biomarkers in relation to 2 weeks administration of low doses of recombinant growth hormone in healthy male volunteers. Moreover, the hematological parameters included in the athlete biological passport were studied as well as the serum concentration of testosterone and dihydrotestosterone. Fibronectin 1 increased by 20% during the treatment period (P ? 0.05), confirming the previous finding. Alpha‐HS‐glycoprotein decreased by 25% up to 3 weeks after treatment (P ? 0.05), contradicting previous results. The addition of fibronectin 1 increased the likelihood of detecting recombinant growth hormone intake based on individual calculated thresholds in some of the participants compared with the GH2000, IGF‐I, and P‐III‐NP. The multiplication of fibronectin 1 concentration by IGF‐I resulted in the most profound (up to 4‐fold) changes. A minor 15% increase (P = 0.003) in the reticulocyte percentage was observed, but the changes did not lead to any atypical profile based on individual passport thresholds. Vitamin D binding protein, decorin, testosterone, and dihydrotestosterone were not affected by growth hormone. Dihydrotestosterone sulfate was negatively correlated with IGF‐I at baseline (R = –0.50, P = 0.003) and post dose (R = –0.59, P = 0.01). In conclusion, fibronectin 1 was verified as a promising future biomarker for detecting low doses of recombinant growth hormone.     

雄激素源性秃发家系调查

目的:研究雄激素源性秃发(androgenetic alopecia,AGA)家系各成员特征,根据其临床表现及家系特点分析,发现雄激素源性脱发的遗传特点。方法:调查该家系共100名成员,AGA患者32例,其中男性30例,女性2例,调查对象的年龄2~78岁。男性与女性分别于28岁左右和58岁左右开始出现大量脱发。结论:发现雄激素源性秃发常会伴随痤疮和其他皮肤附属器疾病在患者的不同年龄阶段发病,且该病在男性中发病率较高,而在女性中发病率较低。雄激素源性秃发遗传方式较接近于从性显性的常染色体遗传,且患者病情严重程度受生活方式的影响。     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Hormonal changes and their impact on cognition and mental health of ageing men

Demographic changes resulting in ageing of the world's population have major implications for health. As men grow older, circulating levels of the principal androgen or male sex hormone testosterone (T) decline, while the prevalence of ill-health increases. Observational studies in middle-aged and older men have shown associations between lower levels of T and poorer mental health in older men, including worse cognitive performance, dementia and presence of depressive symptoms. The role of T metabolites, the more potent androgen dihydrotestosterone (DHT) and the oestrogen receptor ligand estradiol (E2) in the pathophysiology of cognitive decline are unclear. Studies of men undergoing androgen deprivation therapy in the setting of prostate cancer have shown subtle detrimental effects of reduced T levels on cognitive performance. Randomised trials of T supplementation in older men have been limited in size and produced variable results, with some studies showing improvement in specific tests of cognitive function. Interventional data from trials of T therapy in men with dementia are limited. Lower levels of T have also been associated with depressive symptoms in older men. Some studies have reported an effect of T therapy to improve mood and depressive symptoms in men with low or low-normal T levels. T supplementation should be considered in men with a diagnosis of androgen deficiency. Beyond this clinical indication, further research is needed to establish the benefits of T supplementation in older men at risk of deteriorating cognition and mental health.