Functional Significance of Nuclear Estrogen Receptor Subtypes in the Liver of Goldfish

Estrogens work by binding to and activating specific estrogen receptors (ERs). Although mammals have two major nuclear ER subtypes (ERα and ERβ), three subtypes have been shown in teleost fish (ERα, ERβ-I, and ERβ-II). 17β-Estradiol stimulates the production of an egg yolk precursor protein (vitellogenin) in the liver of oviparous species, including the goldfish. However, the functional involvement of the ER subtypes in this process is not fully understood. Here, using primary goldfish hepatocytes, we test the hypothesis that all three ER subtypes are functionally involved in the liver of goldfish by using RNA interference to specifically knock-down the different ER subtypes. The results suggest that ERα is induced by estradiol through activation of the ERβ subtypes. This induction serves to sensitize the liver to further stimulation by estradiol. The knock-down results were supported by use of ER subtype specific antagonists. Sensitization by up-regulation of ERα is likely to be important for seasonal spawners such as goldfish, to bring about a change from somatic growth to reproductive development, and vitellogenesis. The novel data presented in this study provide strong support for the hypothesis that the goldfish ER subtypes play functional roles in the regulation of vitellogenin and ERα and provide a framework for the better understanding of ER signaling in fish and other vertebrates.

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The Evolving Roles of Cardiac Macrophages in Homeostasis, Regeneration, and Repair

International Journal of Molecular Sciences ◽

10.3390/ijms22157923 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7923

Author(s):

Santiago Alvarez-Argote ◽

Caitlin C. O’Meara

Keyword(s):

Cardiac Injury ◽

Cardiac Regeneration ◽

Normal Function ◽

Cardiac Conduction ◽

Cell Detection ◽

Fate Mapping ◽

The Novel ◽

Functional Roles ◽

Macrophage Populations ◽

And Function

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.

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Distinct evolutionary trajectories of V1R clades across mouse species

10.21203/rs.2.22451/v3 ◽

2020 ◽

Author(s):

Caitlin H Miller ◽

Polly Campbell ◽

Michael J Sheehan

Keyword(s):

Positive Selection ◽

House Mouse ◽

Gene Family Evolution ◽

Specific Gene ◽

Receptor Subtypes ◽

Gene Repertoire ◽

Social Signals ◽

Functional Roles ◽

Wide Range ◽

Evolutionary Trajectories

Abstract BACKGROUND: Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus . We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. RESULTS: We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for distinct evolutionary processes across different clades, from largescale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable, as some clades exhibit abundant positive selection while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation. CONCLUSION: Analysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of receptors.

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Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes

Endocrinology ◽

10.1210/endocr/bqaa127 ◽

2020 ◽

Vol 161 (9) ◽

Cited By ~ 12

Author(s):

Franck Mauvais-Jarvis ◽

Sabra L Klein ◽

Ellis R Levin

Keyword(s):

Immune Response ◽

Distress Syndrome ◽

Immune Dysregulation ◽

Innate Immune ◽

The Novel ◽

Cytokine Storm ◽

Inflammatory Infiltration ◽

Biological Sex ◽

17Β Estradiol ◽

Novel Coronavirus

Abstract Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17β-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.

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Downregulation of Estrogen Receptor Gene Expression by Exogenous 17β-Estradiol in the Mammary Glands of Lactating Mice

Experimental Biology and Medicine ◽

10.1177/153537020623100311 ◽

2006 ◽

Vol 231 (3) ◽

pp. 311-316 ◽

Cited By ~ 25

Author(s):

Toshinobu Hatsumi ◽

Yutaka Yamamuro

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Mammary Gland ◽

Single Injection ◽

Receptor Gene ◽

Self Regulation ◽

Estrogen Receptor Gene ◽

17Β Estradiol ◽

Nuclear Estrogen Receptor ◽

Receptor Gene Expression

The biological actions of estrogen are mostly conveyed through interaction with the nuclear estrogen receptor (ER). Previous evidence indicated that estrogen participates in self-regulation through the modulation of the expression of its own receptors. However, the self-regulation of estrogen against ER in the mammary gland during established lactation has not yet been investigated. The present study evaluated ER gene expression in the lactating gland activated by large doses of 17β-estradiol (E2). Repeated E2 treatments dose-dependently decreased the gene, expression of ER, especially its subtype ER-α mRNA, Which was decreased to 10% of the vehicle-injected control by 1 μg E2 injection, whereas it was decreased by 73% for another subtype, ER-β. A single injection of 5 μg of E2 drastically downregulated both ER genes within 12 hrs of injection, and they did not recover to pretreatment level within 48 hrs. Western blot analysis verified that E2 treatment inhibited the phosphorylation of Stat5, which is a potent transcriptional regulator for ER mRNA. The present findings demonstrate that E2 treatment decreases the gene expression of its own receptor in the mammary gland during galactopoesis and induces an apparent transition of the ER profile in the mammary gland during lactation into postlactation.

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Segmental differences in angiotensin receptor subtypes in interlobular artery of hydronephrotic rat kidneys

AJP Renal Physiology ◽

10.1152/ajprenal.1993.265.6.f881 ◽

1993 ◽

Vol 265 (6) ◽

pp. F881-F885 ◽

Cited By ~ 1

Author(s):

K. Hayashi ◽

H. Suzuki ◽

T. Saruta

Keyword(s):

Vessel Diameter ◽

Receptor Subtypes ◽

Ang Ii ◽

Functional Roles ◽

Renal Vasoconstriction ◽

Mediated Action ◽

Renal Microvasculature ◽

Dose Dependent ◽

Rat Kidneys ◽

At2 Receptors

Recent studies demonstrate that angiotensin II (ANG II)-induced vascular action is mediated preferentially by AT1 receptors. Although autoradiographic studies indicate the presence of AT2 receptors in large preglomerular vessels, functional roles for AT2 receptors in ANG II-induced renal vasoconstriction remain undetermined. We examined the effects of DuP-753 and PD-123319 on ANG II-induced vasoconstriction of interlobular arteries (ILA) in isolated perfused hydronephrotic rat kidneys to directly assess the AT1- and AT2-mediated action of ANG II on renal microvessels. Both DuP-753 (0.1-10 microM) and PD-123319 (0.1-10 microM) elicited dose-dependent vasodilation of ANG II-induced ILA constriction, with 86 +/- 4% and 36 +/- 4% inhibition by 10 microM DuP-753 and PD-123319, respectively. The reversal by DuP-753 of ANG II-induced ILA vasoconstriction was greater in small-caliber segments than in large-caliber segments. In contrast, the ability of PD-123319 (10 microM) to inhibit the vasoconstriction was augmented as the vessel diameter increased (slope = +0.46, correlation coefficient = +0.68; P < 0.01). Thus, although AT1 predominantly mediates the ANG II-induced ILA vasoconstriction, PD-123319-sensitive ANG II receptors (e.g., AT2 or AT1B) may also participate partly in the ILA vasoconstriction, particularly at large-caliber segments. In conclusion, distribution of ANG II receptor subtypes may differ depending on the size of the renal microvasculature.

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