The effects of ovarian hormone deficiency on wound contraction in a rat model

Calvin, Melissa; Dyson, Mary; Rymer, J.; Young, Steve

doi:10.1111/j.1471-0528.1998.tb10057.x

Cited by 40 publications

(28 citation statements)

References 24 publications

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“…C, no injection at wound site; PBS, vehicle control. estrogen in maintaining a rapid rate of healing in both animal and human models, suggesting that the marked reduction of estrogen with age in both females and males plays a major role in age-related impaired woundhealing states (2)(3)(4)(5)(6)(7)(8). Moreover, evidence suggests that a crucial mechanism underlying the responses to estrogen involves a dampening of the inflammatory response, resulting in reduced proteolytic activity and enhanced matrix deposition (6).…”

Section: Discussionmentioning

confidence: 99%

Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

Ashcroft¹,

Mills²,

Lei³

et al. 2003

J. Clin. Invest.

284

184

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IntroductionBecause of a complex interaction of medical and epidemiological factors, there has been a rapid increase in the size of the elderly population. With this, there has also been a parallel increase in morbidity associated with age-related delayed wound healing, which costs the health services over $9 billion per year. Cutaneous wound healing is characterized by an initial inflammatory response, followed by reformation of the epithelial barrier and matrix deposition. Accumulating evidence implicates inflammation, and the resultant proteolysis of matrix, as a causative factor in age-related delayed healing and suggests that in the absence of infection, the inflammatory response is inappropriately excessive (1, 2). There is striking evidence from animal studies dating back to 1962 that estrogens play a crucial role in cutaneous wound healing and repair is significantly delayed in its absence, an event characterized by profound leukocyte recruitment during the initial stages of injury and tissue destruction (3-6). Moreover, exogenous estrogen replacement in these animal and human models reverses the effects on healing (6-8). In this regard, recent reports have shown that hormonereplacement therapy (HRT) prevents the development of chronic wounds (both pressure ulcers and venous ulcers) in postmenopausal women (9, 10). Intriguingly, the positive effect of topical estrogen has been shown in both elderly women and men, reflecting the marked decrease in local estrogenic activity secondary to reduced ovarian activity in women, a decline in the adrenal estrogenic precursor dehydroepiandrosterone (DHEA) in men and women, and altered aromatization of systemic precursors to local active estrogen (6).In excessive and chronic inflammatory disorders, the influx of leukocytes occurs unabated, leading to enhanced cytokine and chemokine production, further unchecked leukocyte recruitment, and ultimately proteolytic tissue destruction. Estrogen accelerates the cutaneous wound-healing process, associated with enhanced matrix deposition, rapid epithelialization, and a dampening of the inflammatory response (2-8).One potential downstream target for hormonal effects Characteristic of both chronic wounds and acute wounds that fail to heal are excessive leukocytosis and reduced matrix deposition. Estrogen is a major regulator of wound repair that can reverse agerelated impaired wound healing in human and animal models, characterized by a dampened inflammatory response and increased matrix deposited at the wound site. Macrophage migration inhibitory factor (MIF) is a candidate proinflammatory cytokine involved in the hormonal regulation of inflammation. We demonstrate that MIF is upregulated in a distinct spatial and temporal pattern during wound healing and its expression is markedly elevated in wounds of estrogen-deficient mice as compared with intact animals. Wound-healing studies in mice rendered null for the MIF gene have demonstrated that in the absence of MIF, the excessive inflammation and delayed-healing phenotype associ...

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Section: Discussionmentioning

confidence: 99%

Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

Ashcroft¹,

Mills²,

Lei³

et al. 2003

J. Clin. Invest.

284

184

View full text Add to dashboard Cite

show abstract

“…Estrogens seem to play a crucial role in cutaneous wound healing, which is substantially delayed in their absence (2)(3)(4)(5). Mechanisms of action include enhancement of re-epithelialization (by increasing mitotic rate of epidermal cells), matrix deposition, and neovascularization (2)(3)(4)(5)(10)(11)(12)(13)(14). Estrogens also dampen the initial inflammatory response and reduce collagen degradation during the remodeling phase by inhibiting production of protease by fibroblasts (15).…”

Section: Abramov Correspondence Fertil Steril 2011mentioning

confidence: 99%

“…Because a large proportion of these surgeries are being performed in postmenopausal women, it is essential to understand how estrogen (E) deficiency affects this process. There is striking evidence from animal studies that Es play a crucial role in cutaneous wound healing and that repair is significantly delayed in its absence (2)(3)(4)(5). Reduced E levels have major downstream effects on cellular and tissue responses to injury, including impaired cytokine signal transduction, unchecked inflammation, and altered protein balance (2)(3)(4)(5).…”

mentioning

confidence: 98%

“…There is striking evidence from animal studies that Es play a crucial role in cutaneous wound healing and that repair is significantly delayed in its absence (2)(3)(4)(5). Reduced E levels have major downstream effects on cellular and tissue responses to injury, including impaired cytokine signal transduction, unchecked inflammation, and altered protein balance (2)(3)(4)(5). At present only scant data have been published regarding the role of Es in the wound healing process in the vagina of either animals or humans.…”

mentioning

confidence: 98%

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Effect of bilateral oophorectomy on wound healing of the rabbit vagina

Abramov¹,

Webb²,

Botros³

et al. 2011

Fertility and Sterility

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“…Recentes estudos têm demonstrado impactos deletérios da menopausa sobre a massa óssea e sobre o sistema cardiovascular, bem como a redução destes efeitos pela terapia de reposição hormonal (TRH). Entretanto, os possíveis efeitos da deficiência de hormônios ovarianos neste período sobre a pele e sobre o processo de reparação das feridas ainda é pouco documentado 2 . A reparação tecidual envolve um processo complexo que resulta na substituição do tecido lesado por colágeno e o órgão reparado perde parte de sua funcionabilidade, pois o colágeno não apresenta as mesmas propriedades do tecido em questão.…”

Section: Introductionunclassified

Efeitos da terapia de reposição hormonal na cicatrização de anastomoses de cólon

et al. 2005

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RESUMOObjetivo: Existe coincidência entre os sintomas do climatério e o aparecimento acentuado dos sinais de envelhecimento da pele. Estudos, em modelos animais, mostraram que o estrógeno é uma espécie de mediador crítico na cicatrização de feridas. Os autores apresentam um estudo da influência da terapia de reposição hormonal (TRH) em anastomoses de cólon, feitas em ratas. Métodos: Utilizam 3 grupos de ratas Wistar, um grupo de ooforectomizadas com TRH feita com 50mg de estrógeno e 2 mg de acetato de medroxiprogesterona, um de ooforectomizadas e sem TRH e um de ratas laparotomizadas e não ooforectomizadas. Realizaram a ooforectomia e a confirmação da condição hormonal após 28 dias. Em seguida instituíram a TRH ou de solução fisiológica, diariamente. Após 2 meses fizeram uma colotomia esquerda com anastomose término-terminal e estudaram a resistência e a densidade de colágeno com 7 e 14 dias. Resultados: As anastomoses dos cólons das ratas sem TRH eram menos resistentes do que as do grupo controle tanto no 7.o dia (p=0,0488) como no 14. o dia (p=0,0115). A densidade de colágeno foi menor no 7.o dia (p=0,0210) com menor presença de colágeno I (p=0,0023) e de colágeno III (p=0,0470). No 14.o dia estas diferenças permaneceram significantes. Nas anastomoses dos cólons das ratas com TRH as diferenças, em relação ao grupo controle, não foram significantes. Conclusão: A falta dos hormônios ovarianos leva à menor resistência e atrasa a maturação de anastomoses do cólon, em ratas e estas deficiências são compensadas pela TRH. Descritores: Cicatrização de feridas. Terapia de reposição hormonal. Estrógeno. Progesterona. Colágeno. ABSTRACT Purpose:The symptoms of the climacteric coincide with the marked appearance of signs of skin aging. Studies on animal models have shown that estrogen is a critical mediator in wound healing. The authors report a study of the influence of hormonal replacement therapy (HRT) on colon anastomoses performed in female rats. Methods: Three groups of Wistar rats were used: one submitted to oophorectomy and receiving HRT with 50 mg estrogen and 2 mg medroxyprogesterone acetate, one submitted to oophorectomy without HRT, and one of laparotomized but not oophorectomized rats. Hormonal condition was confirmed 28 days after oophorectomy and HRT or physiological saline was then administered daily. Left colotomy was performed after 2 months with end-to-end anastomosis, and resistance and collagen density were determined after 7 and 14 days. Results: the anastomoses of the colons of rats receiving no HRT were less resistant than those of the control group both on the 7th (p=0.0488) and 14th (p=0.0115) day. Collagen density was lower on the 7 th day (p=0.0210), with a lower presence of collagen I (p=0.0023) and collagen III (p=0.0470), and these differences continued to be significant on the 14 th day. The colon anastomoses of rats receiving HRT did not differ significantly from control. Conclusion: The lack of ovarian hormones leads to a lower resistance and delays the maturation of colon anastomosis in ...

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The effects of ovarian hormone deficiency on wound contraction in a rat model

Cited by 40 publications

References 24 publications

Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

Effect of bilateral oophorectomy on wound healing of the rabbit vagina

Efeitos da terapia de reposição hormonal na cicatrização de anastomoses de cólon

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