Female Sex Steroid Hormones

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The association between obesity and asthma has been particularly strong in adult women and postpubertal girls, suggesting that female sex hormones may be contributing to the increased risk of asthma in obesity (5,28,41). Aromatase, the enzyme responsible for converting androgens to estrogens, is found in adipose tissue. Therefore, it is reasonable to hypothesize that obesity increases estrogen and is associated with early menarche (42), and the risk of developing asthma is particularly strong in girls with early menarche (25). The two different estrogen receptors (ERs), ERa and ER^, are expressed in adipose tissue. In general, estrogen leads to an increase in basal metabolic rate as well as increased ambulatory activity and decreased activity of lipoprotein lipase in laboratory animals. Mice genetically deficient in ERa, as well as those lacking in aromatase, are obese; however, oophorectomized ERa mice have much less fat than intact ERa mice, suggesting that the estrogen signaling through ER^ may promote fat deposition. Although there is some literature on the effect of estrogen on airway responsiveness in animal models, it is unclear how estrogen might impact the development of asthma, but both estrogen and progesterone have been shown to increase IL-4 and IL-13 in peripheral blood mononuclear cells (5,28,41), and there may be other effects on immune or inflammatory cells. Pertaining to sex differences, in mice, O3 induced injury and inflammation of the lungs was enhanced in both male and female Cpefat mice when compared to their respective gender-matched controls, indicating, at least in obese mice, that gender had no impact augmenting response to O3 (34).

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