title: Role of adrenal medulla in development of sexual dimorphism in inflammation.
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 17beta-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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Obstetrics Gynecology and Reproductive Sciences and Medicine, University of California San Francisco, San Francisco, California 94143-0440, USA. paul@itsa.ucsf.edu
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: S R
authors.initials: SR
authors.lastname: Dahlqvist
authors.forename: W M
authors.initials: WM
authors.lastname: Isenberg
authors.forename: F J
authors.initials: FJ
authors.lastname: Miao
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D012739:Gonadal Steroid Hormones / Q000172:deficiency*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D011960:Receptors, Estrogen; D001920:Bradykinin