Testosterone-dependent induction of metallothionein in genital organs of male rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Tohyama C
PROVIDER: S-EPMC1217491 | biostudies-other | 1996 Jul
REPOSITORIES: biostudies-other
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Project description:The present study investigates the protective effects of testosterone against reproductive toxicity induced by cypermethrin (50 mg/kg body weight) in rats. Significant reduction in the testicular and accessory sex organ weights were observed in cypermethrin-treated rats over controls. Cypermethrin intoxication significantly reduced testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability and HOS-tail coiled sperm accompanied by significant reduction in the activity levels of testicular steroidogenic enzymes such as 3β- and 17β- hydroxysteroid dehydrogenases in rats as compared to controls. Further, qPCR studies indicated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR) significantly decreased in cypermethrin-treated rats over controls. Molecular docking analysis indicated that the binding affinity of cypermethrin (- 11.2 kcal/mol) towards StAR protein was greater as compared to its natural ligand, cholesterol (- 8.2 kcal/mol) suggesting improper cholesterol channeling across the testis. Significant reduction in the circulatory levels of testosterone was also recorded in cypermethrin-exposed rats. An increase in pre- and post-implantation loss was observed in rats cohabited with cypermethrin-treated rats. On the other hand, testosterone (4.16 mg/kg body weight) treatment ameliorated cypermethrin-induced reprotoxic effects in rats. To conclude, cypermethrin-induced deterioration of suppressed reproductive performance in male rats could be linked to its antiandrogenic effects and on the other hand, testosterone-mediated protection of male reproductive health in cypermethrin-treated rats at least in part occurs via restoration of testosterone biosynthesis, spermatogenesis and sperm maturation events.
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Project description:The aim of this study was to investigate the involvement of androgen, mainly testosterone, in the expression of renal senescence marker protein-30 (SMP30) in male rats. We found that the renal SMP30 expression was up-regulated by endogenous testosterone stimulation during puberty. Interestingly, androgen-deficient orchidectomized (ORX) rats exhibited lower SMP30 mRNA and protein expression in the kidney, and that was restored by testosterone propionate (TP) replacement. Abrogation of androgen receptor (AR) activity by co-treatment with flutamide abolished testosterone-induced SMP30 expression in the kidney as well as in the NRK52E cells. However, SMP30 expression was unaltered in the liver of ORX rats. We also showed a positive correlation between renal SMP30 expression and plasma testosterone level during the aging process. TP-induced SMP30 expression in ovariectomized (OVX) rats was observed and was an evidence to explain the gender difference of SMP30 levels. Immunofluorescence assay showed that renal SMP30 was specifically expressed in the proximal tubular segments of the kidney. The urinary Ca(2+) level was increased in both ORX and male aging rats. Taken together, our results indicate a novel role of testosterone in regulating SMP30 expression specifically in the kidney to contribute to urinary calcium absorption.
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Project description:Background: Leydig cells secrete the steroid hormone, testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid [corticosterone, (CORT) in rats] that decreases circulating testosterone levels in part through a direct action on its receptors in Leydig cells. Intratesticular CORT level is dependent on oxidative inactivation of CORT by 11?-hydroxysteroid dehydrogenase 1 (HSD11B1) in rat Leydig cells. Pain may cause the stress, thus affecting testosterone production in Leydig cells. Methods: Adult male Sprague-Dawley rats orally received vehicle control or 5 or 10 mg/kg dehydroepiandrosterone (DHEA) 0.5 h before being subjected to pain stimulation for 1, 3, and 6 h. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute pain-induced stress in rats and the possible mechanism of DHEA that prevented it. Plasma CORT, luteinizing hormone (LH), and testosterone (T) levels were measured, and Leydig cell gene expression levels were determined. The direct regulation of HSD11B1 catalytic direction by DHEA was detected in purified rat Leydig, liver, and rat Hsd11b1-transfected COS1 cells. Results: Plasma CORT levels were significantly increased at hour 1, 3, and 6 during the pain stimulation, while plasma T levels were significantly decreased starting at hour 3 and 6. Pain-induced stress also decreased Star, Hsd3b1, and Cyp17a1 expression levels at hour 3. When 5 and 10 mg/kg DHEA were orally administered to rats 0.5 h before starting pain stimulation, DHEA prevented pain-mediated decrease in plasma T levels and the expression of Star, Hsd3b1, and Cyp17a1 without affecting plasma CORT levels. DHEA was found to modulate HSD11B1 activities by increasing its oxidative activity and decreasing its reductive activity, thus decreasing the intracellular CORT levels in Leydig cells. Conclusion: Stress induced by acute pain can inhibit Leydig cell T production by upregulation of corticosterone. DHEA can prevent the negative effects of excessive corticosterone by modulating HSD11B1 activity.
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Project description:While the influence of testosterone levels on vulnerability to affective disorders is not straightforward, research suggests this hormone may confer some degree of resiliency in men. We recently demonstrated a role for the dentate gyrus in mediating testosterone's protective effects on depressive-like behavior in gonadectomized male rats. Here, testosterone may exert its effects through androgen receptor-mediated mechanisms or via local aromatization to estradiol.Gonadectomized male rats were implanted with a placebo, testosterone, or estradiol pellet, and subsequent protective anxiolytic- and antidepressant-like effects of testosterone and its aromatized metabolite, estradiol, were then investigated in the open field and sucrose preference tests, respectively. Moreover, their influence on gene expression in the hippocampus was analyzed by genome-wide complementary DNA microarray analysis. Finally, the contribution of testosterone's aromatization within the dentate gyrus was assessed by local infusion of the aromatase inhibitor fadrozole, whose efficacy was confirmed by liquid chromatography-tandem mass spectrometry.Both hormones had antidepressant-like effects associated with a substantial overlap in transcriptional regulation, particularly in synaptic plasticity- and mitogen-activated protein kinase pathway-related genes. Further, chronic aromatase inhibition within the dentate gyrus blocked the protective effects of testosterone.Both testosterone and estradiol exhibit anxiolytic- and antidepressant-like effects in gonadectomized male rats, while similarly regulating critical mediators of these behaviors, suggesting common underlying mechanisms. Accordingly, we demonstrated that testosterone's protective effects are mediated, in part, by its aromatization in the dentate gyrus. These findings thus provide further insight into a role for estradiol in mediating the protective anxiolytic- and antidepressant-like effects of testosterone.
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Project description:Deficits in coordinated motor behavior and mitochondrial complex V activity have been observed in aged males. Testosterone supplementation can improve coordinated motor behavior in aged males. We investigated the effects of testosterone supplementation on mitochondrial complex V function in the substantia nigra (a brain region that regulates motor activity) in aged male rats. These rats exhibited diminished ATP levels, attenuated mitochondrial complex V activity, and reduced expression of 3 of the 17 mitochondrial complex V subunits (ATP6, ATP8 and ATP5C1) in the substantia nigra. Testosterone supplementation increased ATP levels, mitochondrial complex V activity, and ATP6, ATP8 and ATP5C1 expression in the substantia nigra of the rats. Conversely, orchiectomy reduced mitochondrial complex V activity, downregulated ATP6 and ATP8 expression, and upregulated ATP5C1, ATP5I and ATP5L expression in the substantia nigra. Testosterone replacement reversed those effects. Thus, testosterone enhanced mitochondrial complex V function in the substantia nigra of aged male rats by upregulating ATP6 and ATP8. As potential testosterone targets, these two subunits may to some degree maintain nigrostriatal dopaminergic function in aged males.
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Project description:Biased mating due to female preferences towards certain traits in males is a major mechanism driving sexual selection, and may constitute an important evolutionary force in organisms with sexual reproduction. In birds, although the role of male ornamentation, plumage coloration, genetic dissimilarity, and body size have on mate selection by females have been examined extensively, few studies have clarified exactly how these characteristics affect female mate preferences. Here, we show that testosterone (T)-dependent male attractiveness enhances female preference for males of a polygamous species, the Japanese quail. A significant positive correlation between female mating preference and circulating T in the male was observed. The cheek feathers of attractive males contained higher levels of melanin and were more brightly colored. The ability of females to distinguish attractive males from other males was negated when the light source was covered with a sharp cut filter (cutoff;?<?640?nm). When females were maintained under short-day conditions, the expression of retinal red-sensitive opsin decreased dramatically and they became insensitive to male attractiveness. Our results showed that female preference in quail is strongly stimulated by male feather coloration in a T-dependent manner and that female birds develop a keen sense for this coloration due to upregulation of retinal red-sensitive opsin under breeding conditions.
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Project description:This study evaluated the efficacy of Momordica charantia (MC; bitter melon) extracts against andropause symptoms. We fermented MC with Lactobacillus plantarum and verified the ability of the fermented MC extracts (FMEs) to control testosterone deficiency by using aging male rats as an animal model of andropause. FME administration considerably increased total and free testosterone levels, muscle mass, forced swimming time, and total and motile sperm counts in aging male rats. In contrast, sex hormone-binding globulin, retroperitoneal fat, serum cholesterol, and triglyceride levels were significantly reduced in the treated groups compared to the non-treated control aging male rats. Furthermore, we observed that FME enhanced the expression of testosterone biosynthesis-related genes but reduced the expression of testosterone degradation-related genes in a mouse Leydig cell line. These results suggest that FME has effective pharmacological activities that increase and restore free testosterone levels and that FME may be employed as a promising natural product for alleviating testosterone deficiency syndrome.Supplementary informationThe online version contains supplementary material available at 10.1007/s10068-020-00872-x.
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