Browsing by Subject "Dihydrotestosterone"

Now showing 1 - 5 of 5
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    Differential effects of exercise and hormone treatment on spinal cord injury-induced changes in micturition and morphology of external urethral sphincter motoneurons
    (Sage, 2024) Hibbard, Emily A.; Du, Xiaolong; Zhang, Yihong; Xu, Xiao-Ming; Deng, Lingxiao; Sengelaub, Dale R.; Neurological Surgery, School of Medicine
    Background: Spinal cord injury (SCI) results in lesions that destroy tissue and spinal tracts, leading to deficits in locomotor and autonomic function. We have previously shown that after SCI, surviving motoneurons innervating hindlimb muscles exhibit extensive dendritic atrophy, which can be attenuated by treadmill training or treatment with gonadal hormones post-injury. We have also shown that following SCI, both exercise and treatment with gonadal hormones improve urinary function. Animals exercised with forced running wheel training show improved urinary function as measured by bladder cystometry and sphincter electromyography, and treatment with gonadal hormones improves voiding patterns as measured by metabolic cage testing. Objective: The objective of the current study was to examine the potential protective effects of exercise or hormone treatment on the structure and function of motoneurons innervating the external urethral sphincter (EUS) after contusive SCI. Methods: Gonadally intact young adult male rats received either a sham or a thoracic contusion injury. Immediately after injury, one cohort of animals was implanted with subcutaneous Silastic capsules filled with estradiol (E) and dihydrotestosterone (D) or left blank; continuous hormone treatment occurred for 4 weeks post-injury. A separate cohort of SCI-animals received either 12 weeks of forced wheel running exercise or no exercise treatment starting two weeks after injury. At the end of treatment, urinary void volume was measured using metabolic cages and EUS motoneurons were labeled with cholera toxin-conjugated horseradish peroxidase, allowing for assessment of dendritic morphology in three dimensions. Results: Locomotor performance was improved in exercised animals after SCI. Void volumes increased after SCI in all animals; void volume was unaffected by treatment with exercise, but was dramatically improved by treatment with E + D. Similar to what we have previously reported for hindlimb motoneurons after SCI, dendritic length of EUS motoneurons was significantly decreased after SCI compared to sham animals. Exercise did not reverse injury-induced atrophy, however E + D treatment significantly protected dendritic length. Conclusions: These results suggest that some aspects of urinary dysfunction after SCI can be improved through treatment with gonadal hormones, potentially through their effects on EUS motoneurons. Moreover, a more comprehensive treatment regime that addresses multiple SCI-induced sequelae, i.e., locomotor and voiding deficits, would include both hormones and exercise.
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    Dihydrotestosterone suppression of proinflammatory gene expression in human meibomian gland epithelial cells
    (Elsevier, 2020-04) Sahin, Afsun; Liu, Yang; Kam, Wendy R.; Darabad, Raheleh Rahimi; Sullivan, David A.; Medicine, School of Medicine
    Purpose: We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs. Methods: Differentiated cells were cultured in media containing vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software. Results: Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs. Conclusions: Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.
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    Protective effects of gonadal hormones on spinal motoneurons following spinal cord injury
    (Medknow Publications, 2018-06) Sengelaub, Dale R.; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    Spinal cord injury (SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI. We previously demonstrated that motoneurons, and the muscles they innervate, show pronounced atrophy after SCI. Importantly, SCI-induced atrophy of motoneuron dendrites can be attenuated by treatment with gonadal hormones, testosterone and its active metabolites, estradiol and dihydrotestosterone. Similarly, SCI-induced reductions in muscle fiber cross-sectional areas can be prevented by treatment with androgens. Together, these findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be ameliorated by treatment with gonadal hormones, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.
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    Testosterone does not shorten action potential duration in Langendorff perfused rabbit ventricles
    (Elsevier, 2023-10) Ueoka, Akira; Sung, Yen-Ling; Liu, Xiao; Rosenberg, Carine; Chen, Zhenhui; Everett, Thomas H, IV; Rubart, Michael; Tisdale, James E.; Chen, Peng-Sheng; Pediatrics, School of Medicine
    Background: Women have longer baseline QT intervals than men. Because previous studies showed that testosterone and 5α-dihydrotestosterone shorten the ventricular action potential duration (APD) in animal models, differential testosterone concentrations may account for the sex differences in QT interval. Objective: The purpose of this study was to test the hypothesis that testosterone shortens the APD in Langendorff-perfused rabbit ventricles. Methods: We performed optical mapping studies in hearts with or without testosterone administration. Acute studies included 26 hearts using 2 different protocols, including 17 without and 9 with atrioventricular (AV) block. For chronic studies, we implanted testosterone pellets subcutaneously in 7 female rabbits for 2-3 weeks before optical mapping studies during complete AV block. Six rabbits without pellet implantation served as controls. Results: The hearts in the acute studies were paced with a pacing cycle length (PCL) of 200-300 ms and mapped at baseline and after administration of 1 nM, 10 nM, 100 nM, and 3 μM of testosterone. There was no shortening of APD80 at any PCL. Instead, a lengthening of APD80 was noted at higher concentrations. There were no sex differences in testosterone responses. In chronic studies, heart rates were 136 ± 5 bpm before and 148 ± 9 bpm after (P = .10) while QTc intervals were 314 ± 9 ms before and 317 ± 99 ms after (P = .69) testosterone pellet implantation, respectively. Overall, ventricular APD80 in the pellet group was longer than in the control group at 300- to 700-ms PCL. Conclusion: Testosterone does not shorten ventricular repolarization in rabbit hearts.
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    Testosterone does not shorten action potential duration in Langendorff-perfused rabbit ventricles
    (Elsevier, 2022-11) Ueoka, Akira; Sung, Yen-Ling; Liu , Xiao; Rosenberg, Carine; Chen, Zhenhui; Everett, Thomas H., IV; Rubart , Michael; Tisdale, James E.; Chen, Peng-Sheng; Medicine, School of Medicine
    Background Women have longer baseline QT intervals than men. Because previous studies showed that testosterone and 5α-dihydrotestosterone shorten the ventricular action potential duration (APD) in animal models, differential testosterone concentrations may account for the sex differences in QT interval. Objective The purpose of this study was to test the hypothesis that testosterone shortens the APD in Langendorff-perfused rabbit ventricles. Methods We performed optical mapping studies in hearts with or without testosterone administration. Acute studies included 26 hearts using 2 different protocols, including 17 without and 9 with atrioventricular (AV) block. For chronic studies, we implanted testosterone pellets subcutaneously in 7 female rabbits for 2–3 weeks before optical mapping studies during complete AV block. Six rabbits without pellet implantation served as controls. Results The hearts in the acute studies were paced with a pacing cycle length (PCL) of 200–300 ms and mapped at baseline and after administration of 1 nM, 10 nM, 100 nM, and 3 μM of testosterone. There was no shortening of APD80 at any PCL. Instead, a lengthening of APD80 was noted at higher concentrations. There were no sex differences in testosterone responses. In chronic studies, heart rates were 136 ± 5 bpm before and 148 ± 9 bpm after (P = .10) while QTc intervals were 314 ± 9 ms before and 317 ± 99 ms after (P = .69) testosterone pellet implantation, respectively. Overall, ventricular APD80 in the pellet group was longer than in the control group at 300- to 700-ms PCL. Conclusion Testosterone does not shorten ventricular repolarization in rabbit hearts.