Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of wound samples from rats treated with the 5alpha-reductase inhibitor MK-434

ABSTRACT: The present study aimed to delineate the central mechanisms by which androgens delay wound repair. Blocking the conversion of testosterone to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase limits its ability to impair skin wound healing, suggesting that DHT is a more potent inhibitor of repair than is testosterone. This study aims to identify, through transcription profiling, potential mechanisms by which the 5alpha-reductase inhibitor MK-434 modulates repair. Microarray analysis of wound RNA samples from rats in which the transformation of testosterone to DHT is prevented has identified biological processes and key individual genes through which DHT may contribute to the altered healing profile in such animals. These include genes with putative roles in wound contraction and re-epithelialization.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Leo Zeef

PROVIDER: E-MEXP-1232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization.

Gilliver S C SC Ruckshanthi J P D JP Hardman M J MJ Zeef L A H LA Ashcroft G S GS

The Journal of pathology 20090101 1

The ongoing search for explanations as to why elderly males heal acute skin wounds more slowly than do their female counterparts (and are more strongly disposed to conditions of chronic ulceration) has identified endogenous oestrogens and androgens as being respectively enhancers and inhibitors of repair. We previously demonstrated that blocking the conversion of testosterone to 5alpha-dihydrotestosterone (DHT) limits its ability to impair healing, suggesting that DHT is a more potent inhibitor ...[more]

PMID: 18855875

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Project description:This a model from the article: Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats. Potter LK, Zager MG, Barton HA. Am J Physiol Endocrinol Metab. 2006:91(5):E952-64. 16757547 , Abstract: The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. Understanding these regulatory mechanisms is important for assessing the reproductive effects of environmental and pharmaceutical androgenic and antiandrogenic compounds. A mathematical model for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the adult rodent ventral prostate was developed on the basis of a model by Barton and Anderson (1997). The model describes the systemic and local kinetics of testosterone (T), 5alpha-dihydrotestosterone (DHT), and luteinizing hormone (LH), with metabolism of T to DHT by 5alpha-reductase in liver and prostate. Also included are feedback loops for the positive regulation of T synthesis by LH and negative regulation of LH by T and DHT. The model simulates maintenance of the prostate as a function of hormone concentrations and androgen receptor (AR)-mediated signal transduction. The regulatory processes involved in prostate size and function include cell proliferation, apoptosis, fluid production, and 5alpha-reductase activity. Each process is controlled through the occupancy of a representative gene by androgen-AR dimers. The model simulates prostate dynamics for intact, castrated, and intravenous T-injected rats. After calibration, the model accurately captures the castration-induced regression of the prostate compared with experimental data that show that the prostate regresses to approximately 17 and 5% of its intact weight at 14 and 30 days postcastration, respectively. The model also accurately predicts serum T and AR levels following castration compared with data. This model provides a framework for quantifying the kinetics and effects of environmental and pharmaceutical endocrine active compounds on the prostate. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Potter, Zager, Barton (2006) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@auckland.ac.nz The University of Auckland Auckland Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Dataset Information

Transcription profiling by array of wound samples from rats treated with the 5alpha-reductase inhibitor MK-434

Publications

5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization.

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