Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testosterone -- the gonadal sex steroid hormone plays an important role in the central nervous system (CNS) development. One of the less known testosterone actions is neuroprotection. There are some evidences supporting the hypothesis that testosterone may act protectively in neurodegenerative disorders, e.g. Alzheimer's disease (AD), mild cognitive impairment (MCI) or depression. Androgens alter also the morphology, survival and axonal regeneration of motor neurons. These hormones accelerate the regeneration of hamster facial nerve and anterior tibialis sciatic nerve in rabbits following crush axotomy. Androgens exert trophic action in laryngeal motor nucleus of Xenopus laevis. Testosterone is linked to an increase in neuron somal size, neuritic growth, plasticity and synaptogenesis in both motoneurons of the spinal nucleus of the bulbocavernosus and several populations of pelvic autonomic neurons. The hormone reduced the extent of spinal cord damage in vitro. There are also evidences against the neuroprotective action of testosterone. Testosterone does not protect against methamphetamine-induced neurotoxicity of the dopaminergic system in mice and does not provide significant neuroprotection against glutamate-induced neurotoxicity. Androgens do not prevent striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Although the role of testosterone in the CNS is still poorly understood, accumulating evidence suggests that testosterone may create a future treatment for MCI and related cognitive diseases, including dementia and may influence motor neuron regeneration in adulthood. Androgen replacement therapy in selected male populations may hold therapeutic promise for the prevention and/or treatment of age-related disorders associated with neuronal injury.
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PMID:Neuroprotective role of testosterone in the nervous system. 1559 38

Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-mum-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an approximately 3- to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosterone-mediated suppression of resistance against blood-stage malaria.
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PMID:Testosterone suppresses protective responses of the liver to blood-stage malaria. 1561 82

Anabolic steroids are drugs of abuse. However, the potential for steroid reward and addiction remains largely unexplored. This study used i.c.v. testosterone self-administration and controlled infusions of testosterone or vehicle in hamsters to explore central mechanisms of androgen overdose. Forty-two hamsters used nose-pokes to self-administer 1 microg/microl testosterone i.c.v. 4 h/day in an operant chamber. During 1-56 days of androgen self-administration, 10 (24%) hamsters died. Deaths correlated with peak daily intake of testosterone. Of the hamsters that self-administered a peak intake of <20 microg/day, there was 100% survival (10/10). Survival decreased to 86% (19/22) when daily testosterone intake peaked at 20-60 microg/day. Only 30% (three of 10) survived when daily testosterone intake exceeded 60 microg/day. Deaths are not due to volume or vehicle because i.c.v. infusions of 80 mul vehicle had no effect. Testosterone overdose resembles opiate intoxication. When male hamsters received infusions of 40 microg testosterone, locomotion (25.1+/-18.8 grid-crossings/10 min), respiration (72.7+/-5.4 breaths/min) and body temperature (33.5+/-0.4 degrees C) were significantly reduced, compared with males receiving vehicle infusions (186.1+/-8.1 crossings/10 min, 117.6+/-1.0 breaths/min, 35.9+/-0.1 degrees C, P<0.05). However, males developed tolerance to continued daily testosterone infusion. After 15 days, locomotion (170.2+/-6.3 crossings), respiration (118.4+/-1.3 breaths/min), and body temperature (35.3+/-0.3 degrees C) in testosterone-infused males were equivalent to that in vehicle controls (P>0.05). The depressive effects of testosterone infusion are blocked by the opioid antagonist, naltrexone. With naltrexone pre-treatment (10 mg/kg s.c.), locomotion (183.7+/-1.8 crossings/10 min), respiration (116.9+/-0.3 breaths/min), and body temperature (36.1+/-0.4 degrees C) during testosterone infusion were equivalent to vehicle controls. Likewise, naltrexone prevents the reinforcing effects of i.c.v. testosterone self-administration. These results indicate that testosterone at high doses causes central autonomic depression, which may be a factor in deaths during self-administration. As well, the depressive effects of large quantities of testosterone may be mediated, at least in part, by an opioidergic mechanism.
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PMID:Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms. 1565 94

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.
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PMID:Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia. 1578 56

This study investigated the association of personality with cardiovascular stress reactivity (CVR) in men and women. Also, the degree to which testosterone and estradiol reactivity were related to personality and CVR measures was examined. Twenty-six men and 44 women completed the Cook-Medley Hostility Scale, the Beck Depression Inventory, and the Spielberger Trait Anxiety Inventory before speech, Stroop, and math stress. Testosterone (men) and estradiol (subset of women) were sampled once after an initial rest period and again after the last stressor. Cardiovascular reactivity, including cardiac output and total peripheral resistance (TPR), was assessed during stressors. For men, testosterone increased significantly with stress, and testosterone reactivity to stressors was significantly correlated with hostility. However, stepwise multiple regression revealed that hostility was the only independent predictor of CVR to speech, math, and Stroop stress in men, accounting for 13%-32% of the variance in TPR. Baseline systolic blood pressure explained 22% of the variance in TPR reactivity to speech preparation. No evidence was obtained to suggest that hostility, depressive mood, or anxiety predicted CVR in women, and estradiol did not show stress-sensitive effects. These data provide evidence that increased vascular reactivity may be one mechanism linking hostility to increased cardiovascular mortality in men and support the notion that hostility may have different implications for CVR in women.
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PMID:Hostility, testosterone, and vascular reactivity to stress: effects of sex. 1625 Jul 31

Gerenuk antelope in North American zoos are descended from 28 founders imported from Kenya approximately 20 years ago. Intensive management is required to prevent inbreeding depression. Artificial insemination has potential for augmenting genetic management, but successful application requires a thorough understanding of species' reproductive norms. Semen collected from captive (n = 10) and wild (n = 6) gerenuk contained low numbers of morphologically normal spermatozoa (approximately 40%). Age, but not season, influenced (P < 0.05) the proportion of morphologically normal spermatozoa (mean +/- s.e.m., 12-17 months of age, 10.3 +/- 1.9%; 18-26 months of age, 34.4 +/- 6.2%; 3-6 years of age, 40.0 +/- 4.7%). Seasonality was investigated by analysing faecal testosterone and progesterone in males and females, respectively, by radioimmunoassays. Females cycled all year (ovarian cycle length, 18.7 +/- 0.9 days). Testosterone in males did not vary (P > 0.05) with time of year. Three females (3/9, 33%) became pregnant by insemination with 9.75-54.0 x 0(6) motile fresh or frozen sperm after oestrus synchronisation with two prostaglandin F(2alpha) injections, 12 days apart. One female inseminated with frozen-thawed sperm delivered a full-term stillborn calf after 213 days gestation. These results characterise gerenuk reproductive norms and indicate that artificial insemination may be a useful tool in the genetic management of gerenuk.
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PMID:Reproductive physiology and artificial insemination studies in wild and captive gerenuk ( Litocranius walleri walleri ). 1636 24

The process of urbanization occurring in many developing countries may have consequences for reproductive endocrine function. Here, we test predictions concerning variation in South African male testosterone levels among subgroups across an urbanization gradient representing differences in both geography and socioeconomic status. Subjects included 364 males aged between 20 and 82 comprising a cross-sectional study conducted between 1996 and 1998. Testosterone levels were measured from serum samples obtained between 08:00 and 11:00. In ANCOVA analysis, male testosterone levels differed significantly along this rural-to-urban gradient, with members of the most urban group having higher testosterone levels than groups of farmers and inhabitants of informal housing areas adjacent to towns. Testosterone levels declined with age and were negatively related to body mass index (BMI). Testosterone levels did not differ according to HIV status. Further exploratory ANCOVA analyses revealed that physical activity levels, depression, affect, and hostility were not significantly associated with variation in testosterone levels. These data help document causes of variation in male testosterone levels in a context of urbanization and may have implications for clinical outcomes such as the development of a male hormonal contraceptive or prostate cancer.
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PMID:Predictors of South African male testosterone levels: the THUSA study. 1637 46

Several studies indicate that cell-mediated immune responses, i.e., macrophage (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MPhi cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MPhi was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MPhi from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.
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PMID:Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage. 1661 59

Sexual dysfunction is a frequently encountered comorbid condition in patients with many medical and psychiatric conditions, such as epilepsy and depression. Most depressed patients experience some type of sexual dysfunction, decreased sexual desire being the most common. The association of sexual dysfunction with epilepsy is less clear. Changes in sex hormone levels are common in patients with epilepsy and may be attributable to the disease or to antiepileptic drugs (AEDs). Sexual dysfunction associated with depression or epilepsy is generally treated according to standard guidelines for the management of sexual disorders, since data from special populations are not available. The most common forms of female sexual dysfunction are lack of sexual desire and difficulty achieving orgasm. There are no approved pharmacotherapies for female hypoactive sexual desire disorder or female orgasmic disorder. Female sexual arousal disorder is treated with estrogen replacement therapy when indicated or vaginal lubricants. The most common male sexual dysfunction disorders are premature ejaculation and erectile dysfunction. Phosphodiesterase type-5 inhibitor drugs are now the first-line treatment for erectile dysfunction, and selective serotonin reuptake inhibitors and topical anesthetic creams are nonapproved but effective treatments for premature ejaculation. Testosterone and aromatase inhibitors have been used investigationally to treat sexual dysfunction in men taking AEDs. Patient education and follow-up appointments are essential to ensure optimal outcomes of pharmacologic treatments for sexual dysfunction.
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PMID:Pharmacologic treatment strategies for sexual dysfunction in patients with epilepsy and depression. 1687 Nov 36

Around the menopause, changes in ovarian secretion of steroids result in changes in brain function: hot flushes and sweating later followed by changes in mood, libido and cognition. The relationship between sex steroids and brain functions are reviewed, with focus on hormonal treatments, in particular tibolone, on the postmenopausal brain and on associations between tissue levels and brain functions. Data on steroid levels in human brain are limited. Exogenous oestrogens alone or combined with progestagens reduce hot flushes and sweating, and may favourably affect anxiety, depression and mood. Testosterone alone or combined with E(2) improves libido and mood. Tibolone reduces hot flushes and sweating, and improves mood and libido, but does not stimulate endometrium or breast, like oestrogens. Tibolone is an ideal compound for studying steroid levels and metabolism in brain in view of its structural differences from endogenous steroids and its extensive metabolism required to express its endocrine effects. Brain levels of tibolone metabolites were measured in ovariectomized cynomolgus monkeys receiving tibolone for 36 days. Compared to serum, higher levels of the oestrogenic 3alpha/beta-hydroxytibolone and the androgenic/progestagenic Delta(4)-tibolone, and lower levels of sulphated metabolites are found in various brain regions. The high levels of oestrogenic metabolites in the hypothalamus explain hot flush reduction. Combined with the presence of Delta(4)-tibolone, the tibolone-induced increase in free testosterone through SHBG reduction explains androgenic effects of tibolone on mood and libido. The levels of tibolone metabolites in the monkey brain support tibolone's effects on brain functions.
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PMID:Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone. 1711 82


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