Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors

Shao, Ruijin; Egecioglu, Emil; Weijdegård, Birgitta; Ljungström, Karin; Ling, Charlotte; Fernández-Rodrı́guez, Julia; Billig, Håkan

doi:10.1677/joe.1.06896

Cited by 19 publications

(14 citation statements)

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“…Progesterone receptor transcripts were also very low and flagged as present in only ∼ 30% of the arrays of liver samples. Previous studies have failed to find PR expression in normal liver tissue [15], [16]; although PR has been identified in certain hepatic abnormalities [15], [23]. There are other non-classical P4 receptors [9], [10] that may mediate some of the progesterone actions in liver [9], [17], such as the progesterone receptor component 1 (PGRMC1) that we detected as present in all our microarrays.…”

Section: Discussionmentioning

confidence: 49%

Estradiol and Progesterone Exhibit Similar Patterns of Hepatic Gene Expression Regulation in the Bovine Model

et al. 2013

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Female sex steroid hormones, estradiol-17β (E2-17β) and progesterone (P4) regulate reproductive function and gene expression in a broad range of tissues. Given the central role of the liver in regulating homeostasis including steroid hormone metabolism, we sought to understand how E2-17β and P4 interact to affect global gene expression in liver. Ovariectomized cows (n = 8) were randomly assigned to 4 treatment groups applied in a replicated Latin Square design: 1) No hormone supplementation, 2) E2-17β treatment (ear implant), 3) P4 treatment (intravaginal inserts), and 4) E2-17β combined with P4. After 14 d of treatment, liver biopsies were collected, allowing 28 d intervals between periods. Changes in gene expression in the liver biopsies were monitored using bovine-specific arrays. Treatment with E2-17β altered expression of 479 genes, P4 472 genes, and combined treatment significantly altered expression of 468 genes. In total, 578 genes exhibited altered expression including a remarkable number (346 genes) that responded similarly to E2-17β, P4, or combined treatment. Additional evidence for similar gene expression actions of E2-17ß and/or P4 were: principal component analysis placed almost every treatment array at a substantial distance from controls; Venn diagrams indicated overall treatment effects for most regulated genes; clustering analysis indicated the two major clusters had all treatments up-regulating (172 genes) or down-regulating (173 genes) expression. Thus, unexpectedly, common biological pathways were regulated by E2-17β and/or P4 in liver. This indicates that the mechanism of action of these steroid hormones in the liver might be either indirect or might occur through non-genomic pathways. This unusual pattern of gene expression in response to steroid hormones is consistent with the idea that there are classical and non-classical tissue-specific responses to steroid hormone actions. Future studies are needed to elucidate putative mechanism(s) responsible for overlapping actions of E2-17β and P4 on the liver transcriptome.

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Section: Discussionmentioning

confidence: 49%

Estradiol and Progesterone Exhibit Similar Patterns of Hepatic Gene Expression Regulation in the Bovine Model

et al. 2013

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“…In contrast to our finding that PR-B was dominant in hTECs, Shao and colleagues (13) reported dominant PR-A expression in the mouse lung. This difference might be related to species or strain, tissue examined, or the stage of development (9,13).…”

Section: Discussionmentioning

confidence: 99%

“…In endometrial tissue, PR-A and PR-B dually serve an antiinflammatory role (20). Expression of PR in the lungs has been reported, but cell-specific localization and function has not been characterized (12,13,16,21). …”

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confidence: 99%

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Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Jain

Ray

Pan

et al. 2012

Am J Respir Cell Mol Biol

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Previous studies have demonstrated a female disadvantage in airway diseases, such as asthma and bronchiectasis. The basis for this sex disparity is unknown. We hypothesized that the female sex hormone, progesterone (P4), inhibits functions of the normal airway mucociliary apparatus. P4 receptor (PR) expression was evaluated in human lung and cultured primary human airway epithelial cells isolated from male and female lung transplant donors. PR expression was restricted to the proximal region of the cilia of airway epithelia, and was similar in men and women. Expression of isoform PR-B was more abundant than PR-A in cells from both sexes. Airway epithelial cell exposure to P4 decreased cilia beat frequency (CBF) by 42.3% (67.2). Inhibition of CBF was prevented by coadministration of P4 with the active form of estrogen, 17b-estradiol, or the PR antagonist, mifepristone. P4 inhibition was time and dose dependent, with a significant decrease by 8 hours and maximal effect at 24 hours, accompanied by translocation of PR from the cilia to the nucleus. Inhibition of cilia beat was also prevented by treatment of cells with actinomycin D, suggesting that CBF inhibition is a transcriptionally mediated event. Together, these findings indicate that sex hormones influence the function of a key component of the mucociliary apparatus. These mechanisms may contribute to the sex disparity present in airway diseases and provide therapeutic targets for the treatment of these debilitating airway diseases.Keywords: cilia; progesterone receptor; cilia beat frequency; sex disparity; lung diseaseMultiple epidemiologic studies have established that women have more severe airway disease than men (1, 2). Women with asthma and chronic obstructive lung disease have more frequent and severe exacerbations than men, and a lower disease-specific quality of life (1, 3). Bronchiectasis affects women more commonly, and is more aggressive than in men (2, 4). For example, in cystic fibrosis (CF), a disease in which the impact of bronchiectasis has been extensively studied, women have worse outcomes and a decreased life expectancy compared with men, despite a similar cause of disease. This has been attributed specifically to a greater severity of lung disease, and is present even after adjusting for potentially confounding morphometric, nutritional, compliance, and microbial factors (4, 5). In addition, in models of Pseudomonas aeruginosa infection, one of the most common pathogens found in bronchiectasis, female mice are more affected than males, again for unclear reasons (6). Defects in mucociliary clearance are a central component to the development of bronchiectasis. We, therefore, hypothesize that female sex hormones regulate the mucociliary apparatus.The major female sex hormones, estrogen and progesterone (P4), vary in levels during ovulatory cycles, pregnancy, menopause, and with exogenous delivery. Although their roles in the uterus, ovary, oviduct, and breast have been well studied, expression and function in other tissues are less well desc...

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“…The target regions, including the mediobasal hypothalamus and suprachiasmatic-preoptic area were dissected (limited anteriorly by the optic chiasma, laterally by the hypothalamic fissures, posteriorly by the mammilary bodies, and in depth by the subthalamic sulcus). Tissue protein was prepared as described [48]. Protein concentrations were determined with the BCA protein assay (Pierce, Rockford, IL), using bovine serum albumin as the standard.…”

Section: Methodsmentioning

confidence: 99%

Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

et al. 2009

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Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5α-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4–5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS.

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Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors

Cited by 19 publications

References 70 publications

Estradiol and Progesterone Exhibit Similar Patterns of Hepatic Gene Expression Regulation in the Bovine Model

Estradiol and Progesterone Exhibit Similar Patterns of Hepatic Gene Expression Regulation in the Bovine Model

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

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