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Role of adrenal medulla in development of sexual dimorphism in inflammation

Authors

  • Paul G. Green,

    1. Departments of Oral and Maxillofacial Surgery,
    2. Division of Neuroscience and NIH Pain Center (UCSF), C-522, Box 0440, University of California San Francisco, San Francisco, California 94143–0440, USA
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  • Solbritt Rantapää Dahlqvist,

    1. Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden
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  • William M. Isenberg,

    1. Obstetrics Gynecology and Reproductive Sciences and
    2. Division of Neuroscience and NIH Pain Center (UCSF), C-522, Box 0440, University of California San Francisco, San Francisco, California 94143–0440, USA
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  • Frederick J.-P. Miao,

    1. Departments of Oral and Maxillofacial Surgery,
    2. Division of Neuroscience and NIH Pain Center (UCSF), C-522, Box 0440, University of California San Francisco, San Francisco, California 94143–0440, USA
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  • Jon D. Levine

    1. Departments of Oral and Maxillofacial Surgery,
    2. Medicine, University of California San Francisco, San Francisco, California 94143–0440, USA
    3. Division of Neuroscience and NIH Pain Center (UCSF), C-522, Box 0440, University of California San Francisco, San Francisco, California 94143–0440, USA
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: Dr Paul G. Green, 4NIH/UCSF Pain Center, as above.
E-mail: paul@itsa.ucsf.edu

Abstract

Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17β-oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone.

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