Androgens and estrogens are known to be critical regulators of mammalian physiology and development. While these two classes of steroids share similar structures (in general, estrogens are derived ...from androgens via the enzyme aromatase), they subserve markedly different functions via their specific receptors. In the past, estrogens such as estradiol were thought to be most important in the regulation of female biology, while androgens such as testosterone and dihydrotestosterone were believed to primarily modulate development and physiology in males. However, the emergence of patients with deficiencies in androgen or estrogen hormone synthesis or actions, as well as the development of animal models that specifically target androgen- or estrogen-mediated signaling pathways, have revealed that estrogens and androgens regulate critical biological and pathological processes in both males and females. In fact, the concept of "male" and "female" hormones is an oversimplification of a complex developmental and biological network of steroid actions that directly impacts many organs. In this Review, we will discuss important roles of estrogens in males and androgens in females.
Steroid hormones are produced throughout the phylogenetic tree, from plants to mammals. In the past 40 years, steroid receptors localized to the nucleus have been recognized as being important to ...mediating steroid action in many organs. This action mainly arises from the regulation of key genes that are important for organ development and function. These include but are not limited to genes influencing the reproductive tract, mammary glands, bone, brain, fat differentiation, pituitary hormone regulation, and metabolic effects in many organs. Unfortunately, steroids also promote the development of hormone-responsive cancers, including breast, uterus, and prostate cancer. It has also been shown that steroid receptors exist outside the nucleus in many organs and cells, with unclear impact for normal development, health, and disease. This review describes the evidence from many laboratories that these receptors exist and function with nuclear receptors to provide the full impact of all steroid hormones.
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.
Plasma membrane estrogen receptors Levin, Ellis R
Trends in endocrinology and metabolism,
12/2009, Letnik:
20, Številka:
10
Journal Article
Recenzirano
Odprti dostop
It is now firmly established that estrogen and all sex steroid receptors exist in discrete cellular pools outside the nucleus. Estrogen receptors (ER) have been localized to the plasma membrane where ...both ERα and ERβ function in a wide variety of cells and organs. ERs have also been found in discrete cytoplasmic organelles including mitochondria and the endoplasmic reticulum. In ligand-dependent fashion, each ER pool contributes to the overall, integrated effects of estrogens producing biological outcomes. This review highlights the recent work establishing new roles and targets of membrane ER signaling. Such actions include prevention of vascular injury or cardiac hypertrophy, sexual behavior and pain perception mediated through the central nervous system, osteoblast survival, and fluid resorption in the colon.
Abstract
We present new determinations of the rest-UV luminosity functions (LFs) at
z
= 2–9 to extremely low luminosities (>−14 mag) from a sample of >2500 lensed galaxies found behind the Hubble ...Frontier Fields (HFF) clusters. For the first time, we present faint-end slope results from lensed samples that are fully consistent with blank-field results over the redshift range
z
= 2–9, while reaching to much lower luminosities than possible from the blank-field studies. Combining the deep lensed sample with the large blank-field samples allows us to set tight constraints on the faint-end slope
α
of the
z
= 2–9 UV LFs and its evolution. We find a smooth flattening in
α
from −2.28 ± 0.10 (
z
= 9) to −1.53 ± 0.03 (
z
= 2) with cosmic time (
dα
/
dz
= −0.11 ± 0.01), fully consistent with dark matter halo buildup. We utilize these new results to present new measurements of the evolution in the
UV
luminosity density
ρ
UV
brighter than −13 mag from
z
∼ 9 to
z
∼ 2. Accounting for the star formation rate (SFR) densities to faint luminosities implied by our LF results, we find that unobscured star formation dominates the SFR density at
z
≳ 4, with obscured star formation dominant thereafter. Having shown we can quantify the faint-end slope
α
of the LF accurately with our lensed HFF samples, we also quantify the apparent curvature in the shape of the UV LF through a curvature parameter
δ
. The constraints on the curvature
δ
strongly rule out the presence of a turn-over brighter than −13.1 mag at
z
∼ 3, −14.3 mag at
z
∼ 6, and −15.5 mag at all other redshifts between
z
∼ 9 and
z
∼ 2.
Steroid hormone receptors mediate numerous crucial biological processes and are classically thought to function as transcriptional regulators in the nucleus. However, it has been known for more than ...50 years that steroids evoke rapid responses in many organs that cannot be explained by gene regulation. Mounting evidence indicates that most steroid receptors in fact exist in extranuclear cellular pools, including at the plasma membrane. This latter pool, when engaged by a steroid ligand, rapidly activates signals that affect various aspects of cellular biology. Research into the mechanisms of signalling instigated by extranuclear steroid receptor pools and how this extranuclear signalling is integrated with responses elicited by nuclear receptor pools provides novel understanding of steroid hormone signalling and its roles in health and disease.
Extra-nuclear steroid receptors mediate steroid hormone functions in brain, bone, cancer, and the cardiovascular system through epigenetic modulation of genes and non-genomic effects.
Steroid ...receptors existing outside the nucleus are increasingly being recognized in many organs and cell types, impacting the biology of bone, the heart and blood vessels, and the central nervous system. Some controversy exists as to the nature of the receptors at the plasma membrane. However, compelling evidence has been advanced that at least some classical steroid receptors mediate steroid ligand actions originating as signaling from the cell surface. Here I review the recent findings in this evolving field emphasizing the in vivo impact of these receptor pools with a focus on estrogen receptors.
The main purpose of this article is to review studies that have investigated the effects of three types of planning (rehearsal, pre-task planning, and within-task planning) on the fluency, ...complexity, and accuracy of L2 performance. All three types of planning have been shown to have a beneficial effect on fluency but the results for complexity and accuracy are more mixed, reflecting both the type of planning and also the mediating role of various factors, including task design and implementation variables and individual difference factors. A secondary purpose is to outline a theory that can account for the role that planning plays in L2 performance. The article concludes with a list of limitations in the research to date.
Relativistic Cosmology Ellis, George F. R.; Maartens, Roy; MacCallum, Malcolm A. H.
03/2012
eBook
Cosmology has been transformed by dramatic progress in high-precision observations and theoretical modelling. This book surveys key developments and open issues for graduate students and researchers. ...Using a relativistic geometric approach, it focuses on the general concepts and relations that underpin the standard model of the Universe. Part I covers foundations of relativistic cosmology whilst Part II develops the dynamical and observational relations for all models of the Universe based on general relativity. Part III focuses on the standard model of cosmology, including inflation, dark matter, dark energy, perturbation theory, the cosmic microwave background, structure formation and gravitational lensing. It also examines modified gravity and inhomogeneity as possible alternatives to dark energy. Anisotropic and inhomogeneous models are described in Part IV, and Part V reviews deeper issues, such as quantum cosmology, the start of the universe and the multiverse proposal. Colour versions of some figures are available at www.cambridge.org/9780521381154.
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