scholarly journals Sex Disparities in Cystic Fibrosis: Review on the Effect of Female Sex Hormones on Lung Pathophysiology and Outcomes

2020 ◽  
pp. 00475-2020
Author(s):  
G.Y. Lam ◽  
J. Goodwin ◽  
P.G. Wilcox ◽  
B.S. Quon
Keyword(s):  
Cystic Fibrosis ◽  
Sex Differences ◽  
Sex Hormones ◽  
Mucociliary Clearance ◽  
Therapeutic Interventions ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Sex Disparities

Sex differences in morbidity and mortality have been reported in the cystic fibrosis (CF) population worldwide. However, it is unclear why CF women have worse clinical outcomes than men. In this review, we focus on the influence of female sex hormones on CF pulmonary outcomes and summarise data from in vitro and in vivo experiments on how estrogen and progesterone might modify mucociliary clearance, immunity and infection in the CF airways. The potential for novel sex hormone related therapeutic interventions is also discussed.

Mucus clearance: in vivo canine tracheal vs. in vitro bullfrog palate studies

1977 ◽  
Vol 42 (5) ◽  
pp. 761-766 ◽  
Author(s):  
A. Giordano ◽  
C. K. Shih ◽  
D. S. Holsclaw ◽  
M. A. Khan ◽  
M. Litt
Keyword(s):  
Cystic Fibrosis ◽  
Mucociliary Clearance ◽  
Objective Method ◽  
Flow Properties ◽  
Therapeutic Modalities ◽  
Mucus Clearance ◽  
Clearance Studies ◽  
Frog Palate

Tracheal mucociliary clearance was studied by a radioisotope technique in pentothal-anesthetized beagles in the control, atropinized, or dehydrated state. Mucus collected from a tracheal pouch in each dog was used for in vitro bullfrog (Rana cantesbiana) palate clearance studies and compared to the in vivo clearance rates. In all three experimental states, there was a significant correlation between in vivo and in vitro rates, suggesting that tracheal pouch mucus is a good model for investigating the mucociliary flow properties of intact airway mucus. When compared to matched controls, atropine appeared to cause a slowing of the in vivo clearance rate but not of the in vitro rate. Dehydration had no effect on either. The appropriateness of the frog palate method in the study of human respiratory disease (e.g., chronic bronchitis, cystic fibrosis) as well as its potential as an objective method of assessing the effects of various therapeutic modalities in these diseases is discussed.

Inhibition of lower esophageal sphincter circular muscle by female sex hormones.

1978 ◽  
Vol 234 (3) ◽  
pp. E243 ◽  
Author(s):  
R S Fisher ◽  
G S Roberts ◽  
C J Grabowski ◽  
S Cohen
Keyword(s):  
Lower Esophageal Sphincter ◽  
Sex Hormones ◽  
Circular Muscle ◽  
Response Curves ◽  
Circular Smooth Muscle ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Esophageal Sphincter ◽  
Muscle Responses

To determine the effect of estrogenic and progesteronic activity on lower esophageal sphincter (LES) circular muscle, studies were performed on 20 adult opossums. Does-response curves on circular smooth muscle strips from the LES were constructed for gastrin and acetylcholine alone, and with 17beta-estradiol and/or progesterone added. Each female hormone significantly decreased the maximal LES muscle responses to gastrin and acetylcholine. A combination of 17beta-estradiol and progesterone abolished the response to gastrin. In contrast, the male sex hormone, dihydrotestosterone, had no effect. In conclusion, administration of estrogen and progesteron, but not dihydrotestosterone, in vitro reduced LES muscle responses to gastrin and acetylcholine. These studies suggest that the female sex hormones can alter LES function and potentially may be of importance in the pathogenesis of heartburn of pregnancy.

Sex Differences in the Pharmacokinetics of Antidepressants: Influence of Female Sex Hormones and Oral Contraceptives

2014 ◽  
Vol 53 (6) ◽  
pp. 509-519 ◽  
Author(s):  
Valérie A. Damoiseaux ◽  
Johannes H. Proost ◽  
Vincent C. R. Jiawan ◽  
Barbro N. Melgert
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Oral Contraceptives ◽  
Female Sex ◽  
Female Sex Hormones

scholarly journals Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes

2021 ◽  
Vol 22 (12) ◽  
pp. 6358
Author(s):  
Andreja Moset Zupan ◽  
Carolyn Nietupski ◽  
Stacey C. Schutte
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Elastic Fibers ◽  
Skin Substitutes ◽  
Estradiol Treatment ◽  
Male And Female ◽  
Female Sex ◽  
Dermal Substitutes ◽  
Female Sex Hormones ◽  
17Β Estradiol

Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.

Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy

1995 ◽  
Vol 268 (1) ◽  
pp. G107-G115 ◽  
Author(s):  
S. Grimbert ◽  
C. Fisch ◽  
D. Deschamps ◽  
A. Berson ◽  
B. Fromenty ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Liver ◽  
Palmitic Acid ◽  
Sex Hormones ◽  
Tricarboxylic Acid Cycle ◽  
Liver Mitochondria ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Acute Fatty Liver

Acute fatty liver of pregnancy occurs in some women. As other cases of microvesicular steatosis are due to impaired mitochondrial oxidation of fatty acids, we investigated the effects of female sex hormones on liver mitochondria in female mice. Three hours after administration of both estradiol (36 mumol/kg) and progesterone (150 mumol/kg), the in vitro beta-oxidation of [U-14C]palmitic acid and the activity of the tricarboxylic acid cycle decreased 49 and 54%, whereas the in vivo oxidation of [U-14C]palmitic acid decreased 38%. One week of treatment with both sex hormones produced ultrastructural lesions of mitochondria, decreased the recovery of mitochondrial proteins by 34%, increased state 4 respiration by 54-77%, and decreased the activities per gram of liver of several enzymes involved in the activation, mitochondrial uptake, and oxidation of fatty acids by 34-54%. We conclude that female sex hormones have deleterious effects on liver mitochondria and suggest that these effects, together with other factors, may contribute to the development of acute fatty liver of pregnancy in some women.

scholarly journals Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis

2021 ◽  
Vol 28 (1) ◽  
pp. 155-188
Author(s):  
Massimo Conese ◽  
Sante Di Gioia
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Wound Repair ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Interventions ◽  
In Vivo Studies ◽  
Mesenchymal Transition ◽  
Molecular Events

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions.

Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro

2020 ◽  
Vol 66 (6) ◽  
pp. 444-449
Author(s):  
A.V. Shchulkin ◽  
I.V. Chernykh ◽  
N.M. Popova ◽  
A.A. Slepnev ◽  
E.N. Yakusheva
Keyword(s):  
Sex Hormones ◽  
Constitutive Androstane Receptor ◽  
Direct Inhibition ◽  
Protein Activity ◽  
Transporter Protein ◽  
Female Sex ◽  
Female Sex Hormones ◽  
P Glycoprotein ◽  
Increased Activity

The effects of female sex hormones estradiol and progesterone on P-glycoprotein (Pgp) functioning have been investigated using Caco-2 cells. Pgp activity was analyzed in a transwell system by the transport of its substrate, fexofenadine. The amount of the transporter protein was analyzed by enzyme immunoassay. Incubation of Caco-2 cells with 10 μM estradiol and incubation for 3 days increased activity and synthesis of Pgp. Moreover, this effect was suppressed by the inhibitor of the constitutive androstane receptor (CAR) CINPA 1. Incubation of these cells with 100 μM progesterone for 3 days increased Pgp synthesis, but its activity remained unchanged due to non-genomic (direct) inhibition of Pgp molecule by gestagen. The pregnan-X receptor inhibitor (PXR), ketoconazole suppressed the inducing effect of progesterone on Pgp synthesis. The combination of 10 μM estradiol and 100 μM progesterone increased Pgp synthesis, but did not increase the transporter protein activity, due to direct inhibition of the Pgp molecule by progestogen. Thus, it was found that estradiol increased activity and synthesis of Pgp by stimulating CAR, and progesterone stimulated transporter protein synthesis by activating PXR.

scholarly journals Endocrine regulation of lung disease and inflammation

2018 ◽  
Vol 243 (17-18) ◽  
pp. 1313-1322 ◽  
Author(s):  
Nathalie Fuentes ◽  
Patricia Silveyra
Keyword(s):  
Sex Differences ◽  
Lung Function ◽  
Lung Disease ◽  
Sex Hormones ◽  
Lung Diseases ◽  
Endocrine Regulation ◽  
Male And Female ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Chronic Lung Diseases

Sex-based disparities have been identified in respiratory physiology, and in many chronic lung diseases including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. The observed sex differences in lung disease prevalence and incidence have been linked to changes in circulating levels of sex hormones that start after puberty and that have been shown to affect physiological and immunological functions. While the exact roles of male and female sex hormones in these processes have not been fully elucidated, it is now evident that these can target many lung cell types and affect several functions of the respiratory system. In this mini-review, we have summarized seminal studies aimed to understand the effects of the most relevant male and female sex hormones (estrogens, progesterone, and androgens) and their receptors on lung function. Moreover, we have reviewed the known influences of sex hormones and of the hypothalamic–pituitary–gonadal axis in lung disease and immunity. Understanding the roles of sex hormones in the regulation of lung function and inflammation is the first step for the potential development of more effective therapeutic options to prevent and treat lung disease in men and women. Impact statement Sex-differences in the incidence and severity of inflammatory lung diseases have been recognized for years. Women of reproductive age are more likely to suffer from chronic lung disease, with higher mortality rates than men. Physiological changes in hormone levels such as those occurring during the menstrual cycle, pregnancy, and menopause have been associated with lung function changes and asthma symptoms. Despite this, the roles of sex hormones in the mechanisms associated with lung diseases have not been fully elucidated. This review summarizes basic and clinical studies of sex hormones as potential modulators of lung function and inflammation. The information obtained from sex-specific research on lung physiology and pathology will potentially help in the development of sex-specific therapeutics for inflammatory lung disease that may account for the hormonal status of the patient.

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