Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing

Bibliographic Details
Main Author: Head, Cynthia C.
Language:English
Published: The Ohio State University / OhioLINK 2007
Subjects:
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1186957947
id ndltd-OhioLink-oai-etd.ohiolink.edu-osu1186957947
record_format oai_dc
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu11869579472021-08-03T05:52:35Z Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing Head, Cynthia C. Wound healing steroid hormones androstenediol glucocorticoids inflammation Nuclear factor-kappa B Stress impaired wound healing <p>Stress activates the hypothalamic-pituitary-adrenal (HPA) axis resulting in increased serum glucocorticoids (GCs); GCs are used clinically for their potent anti-inflammatory actions. Thus, because the stress-induced increase in GC is anti-inflammatory, stress predictably suppresses the inflammatory phase of wound healing and slows closure of cutaneous wounds. Previous studies from this laboratory suggest that the steroid hormone dehydroepiandrosterone (DHEA) and its metabolites androstenediol (AED) and androstenetriol (AET) counter-regulate the immune-suppressive functions of GCs. Thus we hypothesized that pharmacological treatment of animals with AED would diminish the health adverse effects of elevated GCs. It is further hypothesized that by counterbalancing the GC-mediated transcriptional regulation of cytokine gene expression through interactions with the transcriptional activator NF-κB, AED will restore inflammation and improve wound healing in stressed animals.</p> <p>A murine model of cutaneous wound healing was used. Male CD-1 mice underwent daily cycles of restraint stress (RST), which began three days prior to wounding. Animals were treated with AED at 3 timepoints, while control animals received vehicle treatment. Photoplanimetry was utilized to assess healing kinetics of the wounds. Wounds were harvested at various times and processed for real time PCR analysis, or the TransAM™ assay.</p> <p>The results show that RST delayed wound closure and altered the kinetics of inflammatory gene expression compared to control animals and did so by modulating NF-κB activation. Treatment with AED prevented the anti-inflammatory effects of RST and augmented NF-κB driven gene expression above control levels. Preliminary data suggest the effects of AED are manifest at the level of transcription initiation complex formation, and future studies will test this hypothesis. In conclusion, the data indicate that AED may be a viable pharmacological approach to functionally antagonize the effects of stress and presumably glucocorticoids, thereby improving wound healing.</p> 2007-08-30 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1186957947 http://rave.ohiolink.edu/etdc/view?acc_num=osu1186957947 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Wound healing
steroid hormones
androstenediol
glucocorticoids
inflammation
Nuclear factor-kappa B
Stress impaired wound healing
spellingShingle Wound healing
steroid hormones
androstenediol
glucocorticoids
inflammation
Nuclear factor-kappa B
Stress impaired wound healing
Head, Cynthia C.
Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
author Head, Cynthia C.
author_facet Head, Cynthia C.
author_sort Head, Cynthia C.
title Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
title_short Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
title_full Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
title_fullStr Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
title_full_unstemmed Hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
title_sort hormonal regulation of cutaneous wound healing: effect of androstenediol on stress impaired wound healing
publisher The Ohio State University / OhioLINK
publishDate 2007
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1186957947
work_keys_str_mv AT headcynthiac hormonalregulationofcutaneouswoundhealingeffectofandrostenediolonstressimpairedwoundhealing
_version_ 1719426968681709568