Sex Hormone Signaling in the Lung in Health and Disease: Airways, Parenchyma, and Pulmonary Vasculature

Frump, Andrea L.; Lahm, Tim

doi:10.1007/978-3-319-23998-9_2

Cited by 4 publications

(5 citation statements)

References 222 publications

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“…Endogenous estrogens include estrone (E1), 17-β-estradiol (E2), and estriol (E3), with E2 being the major form present in adult females and males while E3 is present at high levels in pregnancy ( 7 ). Testosterone is synthesized in both females and males and is converted by 5α-reductase to the physiologically active metabolite dihydrotestosterone (DHT) or by aromatase to estradiol ( 8 ).…”

Section: Sex Hormones and Receptor Signalingmentioning

confidence: 99%

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

2018

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Sex differences in the incidence and severity of respiratory virus infection are widely documented in humans and murine models and correlate with sex biases in numbers and/or functional responses of innate immune cells in homeostasis and lung infection. Similarly, changes in sex hormone levels upon puberty, pregnancy, and menopause/aging are associated with qualitative and quantitative differences in innate immunity. Immune cells express receptors for estrogens (ERα and ERβ), androgens (AR), and progesterone (PR), and experimental manipulation of sex hormone levels or receptors has revealed that sex hormone receptor activity often underlies sex differences in immune cell numbers and/or functional responses in the respiratory tract. While elegant studies have defined mechanistic roles for sex hormones and receptors in innate immune cells, much remains to be learned about the cellular and molecular mechanisms of action of ER, PR, and AR in myeloid cells and innate lymphocytes to promote the initiation and resolution of antiviral immunity in the lung. Here, we review the literature on sex differences and sex hormone regulation in innate immune cells in the lung in homeostasis and upon respiratory virus infection.

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Section: Sex Hormones and Receptor Signalingmentioning

confidence: 99%

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

2018

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“…In addition to the immune response [ 59 ], sex hormones have been shown to influence lung function, the course of disease, and the response to environmental agents (e.g., O 3 ) in animal models and in humans [ 21 ]. E 2 is the major form of estrogen and DHT is the active form of testosterone in adult females and males, respectively [ 59 ]. In the current study, Gx females and Gx males received DHT and E 2 , respectively.…”

Section: Discussionmentioning

confidence: 99%

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

et al. 2020

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Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O3) and sex, as well as gonadal hormones, on the bronchoalveolar lavage (BAL) readouts and survival, respectively, of Klebsiella pneumoniae-infected SP-A KO mice. Male and female SP-A KO mice were exposed to O3 or filtered air and infected with K. pneumoniae. We studied markers of inflammation and tissue damage at 4, 24, and 48 h, as well as the survival over 14 days, of gonadectomized (Gx) mice implanted with control pellets (CoP) or hormone (5α-dihydrotestosterone (DHT) in female gonadectomized mice (GxF) or 17β-estradiol (E2) in male gonadectomized mice (GxM)). We observed: (1) an increase in neutrophil and macrophage inflammatory protein-2 levels as time progressed post-infection, and O3 exposure appeared to increase this response; (2) an increase in lactate dehydrogenase, total protein, oxidized protein, and phospholipids in response to O3 with no consistent sex differences in studied parameters; and (3) a reduction in survival of the GxM and CoP mice, the GxM and E2 mice, and the GxF and DHT mice but not for the GxF and CoP mice after O3. Without SP-A, (a) sex was found to have a minimal impact on BAL cellular composition and tissue damage markers, and (b) the impact of gonadal hormones on survival was found to involve different mechanisms than in the presence of SP-A.

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“…They are primarily produced by the three main organ systems—namely, the gonads, the adrenal glands, and the fetoplacental unit (Carey et al 2007b , c ). However, they have also been known to be metabolized in several nonendocrine peripheral tissues and organ systems (Koledova and Khalil 2007 ; Townsend et al 2012a ; Sathish et al 2015 ; Frump and Lahm 2016 ; Fuentes and Silveyra 2019 ). The local production of sex steroids within specific tissues, mainly from nongonadal sources, depends on the concentration of the enzymes in cholesterol metabolism.…”

Section: Biology Of Sex Steroidsmentioning

confidence: 99%

“…Additionally, male sex is considered a major risk factor among the early childhood group, with the risk of developing chronic asthma being four-fold greater for boys than it is for girls until the age of 14 (Townsend et al 2012a ; Zein and Erzurum 2015 ; Yung et al 2018 ). A number of studies have shown that respiratory allergic diseases are also prevalent in males during childhood, whereas they become more frequent and severe in females between adolescence and adulthood, indicating a major role of sex steroids as critical modulators of the immune response (Humbert et al 2006 ; Martinez et al 2012 ; Frump and Lahm 2016 ; Fuentes and Silveyra 2018 ; Barbagelata et al 2019 ). Risk factors for childhood asthma include both genetic and environmental aspects—for example, prenatal complications in the infant breathing leading to RDS (Bonnet et al 2009 ), child’s gender, and the presence of atopy (Trivedi and Denton 2019 ).…”

Section: Functions Of Sex Steroids Across the Lifespan: An Emphasis Omentioning

confidence: 99%

Sex Steroids and Their Influence in Lung Diseases Across the Lifespan

Borkar

Sathish

2021

Physiology in Health and Disease

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The economic burden of lung diseases continues to be on the rise, with increasing annual expenditures every year. However, the pathophysiology of lung diseases remains complex. Sex steroids are known to influence the development and the physiology of lungs across the life course. During puberty, there is a progressive increase in sex-steroid levels, which results in anatomical and physiological differences between the sexes, and the interactions are most likely causes of the observable sexual dimorphism in the incidence, prevalence, and severity of multiple lung pathologies. Notably, fluctuations during the menstrual cycle and pregnancy impact many lung pathologies, suggesting a link between female sex steroids and lung health. This chapter highlights the influence of sex steroids in lung diseases across the lifespan, adding to our understanding of their complex roles. Focusing on various time points, we aim to understand the following: (1) the inherent function of sex steroids in lung physiology, (2) their differential nature in lung diseases, (3) contribution of sex steroids in males versus females across the lifespan, (4) the implications of sex-steroid signaling, and (5) the probing questions on sex steroids and their interactions influencing the lungs. With the intention of appreciating the nuances of sex steroids in humans pertaining to epidemiological sex differences, we inform readers about the mechanisms involved in the sex–age interaction and sex steroids’ contributions in lung diseases across the lifespan.

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Sex Hormone Signaling in the Lung in Health and Disease: Airways, Parenchyma, and Pulmonary Vasculature

Cited by 4 publications

References 222 publications

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

Sex Hormones Regulate Innate Immune Cells and Promote Sex Differences in Respiratory Virus Infection

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

Sex Steroids and Their Influence in Lung Diseases Across the Lifespan

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