Vitamins and Hormones最新文献

Stress responses to physical, psychological, environmental, or cellular stressors, has two arms: initiation and recovery. Corticotropin-releasing factor (CRF) is primarily responsible for regulating and/or initiating stress responses via, whereas urocortins (UCNs) are involved in the recovery response to stress via feedback inhibition. Stress is a loaded, polysemous word and is experienced in a myriad of ways. Some stressors are good for an individual, in fact essential, whereas other stressors are associated with bad outcomes. Perceived stress, like beauty, lies in the eye of the beholder, and hence the same stressor can result in individual-specific outcomes. In mammals, there are two main biological sexes with reproduction as primary function. Reproduction and nutrition can also be viewed as stressors; based on a body of work from my laboratory, we propose that the functions of all other organs have co-evolved to optimize and facilitate an individual's nutritional and reproductive functions. Hence, sex differences in physiologically relevant outcomes are innate and occur at all levels- molecular, endocrine, immune, and (patho)physiological. CRF and three UCNs are peptide hormones that mediate their physiological effects by binding to two known G protein-coupled receptors (GPCRs), CRF₁ and CRF₂. Expression and function of CRF family of hormones and their receptors is likely to be sexually dimorphic in all organs. In this chapter, based on the large body of work from others and my laboratory, an overview of the CRF family with special emphasis on sex-specific actions of peripherally expressed CRF₂ receptor in health and disease is provided.

Thyroid hormone (T3) plays critical roles in organ metabolism and development in vertebrates. Anuran metamorphosis is perhaps the most dramatic and best studied developmental process controlled by T3. Many changes in different organs/tissues during anuran metamorphosis resemble the maturation/remodeling of the corresponding organs/tissues during mammalian postembryonic development. The plasma T3 level peaks during both anuran metamorphosis and mammalian postembryonic development. T3 exerts its developmental function through transcriptional regulation via T3 receptors (TRs). Studies on the metamorphosis of two highly related anurans, pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, have led to a dual function model for TRs during development. This has been supported by strong molecular and genetic evidence. Here we review some of the evidence with a focus on more recent gene knockout studies in Xenopus tropicalis. These studies have not only supported the model but also revealed novel and TR subtype-specific roles during Xenopus development, particularly a critical role of TRα in controlling developmental timing and rate.

Type 2 diabetes (T2D) is a metabolic disease characterized by the development of β-cell dysfunction with hepatic, muscular and adipose tissue insulin resistance. Although the molecular mechanisms leading to its development are not entirely known, investigations of its causes reveal a multifactorial contribution to its development and progression in most cases. In addition, regulatory interactions mediated by epigenetic modifications such as DNA methylation, histone tail modifications and regulatory RNAs have been found to play a significant role in the etiology of T2D. In this chapter, we discuss the role of DNA methylation and its dynamics in the development of the pathological features of T2D.

Endometriosis is a benign gynecological disease affecting ∼10% of reproductive-aged women and is defined as the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis can cause a variety of health problems, from pelvic discomfort to catamenial pneumothorax, but it's mainly linked with severe and chronic pelvic pain, dysmenorrhea, and deep dyspareunia, as well as reproductive issues. The pathogenesis of endometriosis involves an endocrine dysfunction, with estrogen dependency and progesterone resistance, and inflammatory mechanism activation, together with impaired cell proliferation and neuroangiogenesis. The present chapter aims to discuss the main epigenetic mechanisms related to estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis. There are numerous epigenetic mechanisms participating in endometriosis, regulating the expression of the genes encoding these receptors both indirectly, through the regulation of transcription factors, and directly, through DNA methylation, histone modifications, micro RNAs and long noncoding RNAs. This represents an open field of investigation, which may lead to important clinical implications such as the development of epigenetic drugs for the treatment of endometriosis and the identification of specific and early biomarkers for the disease.

Hormones have been considered as key factors involved in the maintenance of the redox status of the body. We are making considerable progress in understanding interactions between the endocrine system, redox status, and oxidative stress with the dynamics of life, which encompasses fertilization, development, growth, aging, and various pathophysiological states. One of the reasons for changes in redox states of vertebrates leading to oxidative stress scenario is the disruption of the endocrine system. Comprehending the dynamics of hormonal status to redox state and oxidative stress in living systems is challenging. It is more difficult to come to a unifying conclusion when some hormones exhibit oxidant properties while others have antioxidant features. There is a very limited approach to correlate alteration in titers of hormones with redox status and oxidative stress with growth, development, aging, and pathophysiological stress. The situation is further complicated when considering various tissues and sexes in vertebrates. This chapter discusses the beneficial impacts of hormones with antioxidative properties, such as melatonin, glucagon, insulin, estrogens, and progesterone, which protect cells from oxidative damage and reduce pathophysiological effects. Additionally, we discuss the protective effects of antioxidants like vitamins A, E, and C, curcumin, tempol, N-acetyl cysteine, α-lipoic acid, date palm pollen extract, resveratrol, and flavonoids on oxidative stress triggered by hormones such as aldosterone, glucocorticoids, thyroid hormones, and catecholamines. Inflammation, pathophysiology, and the aging process can all be controlled by understanding how antioxidants and hormones operate together to maintain cellular redox status. Identifying the hormonal changes and the action of antioxidants may help in developing new therapeutic strategies for hormonal imbalance-related disorders.

Follicle-stimulating hormone (FSH) and estrogens are fundamental to support reproductive functions. Beside the well-known FSH membrane receptor (FSHR), a G protein-coupled estrogen receptor (GPER) has been found, over the last two decades, in several tissues. It may trigger rapid, non-genomic responses of estradiol, activating proliferative and survival stimuli. The two receptors were co-characterized in the ovary, where they modulate different intracellular signaling cascades, according to the expression level and developmental stage of ovarian follicles. Moreover, they may physically interact to form heteromeric assemblies, suggestive of a new mode of action to regulate FSH-specific signals, and likely determining the follicular fate between atresia and dominance. The knowledge of FSH and estrogen membrane receptors provides a new, deeper level of comprehension of human reproduction.

Arginine-vasopressin (AVP) and oxytocin (OT) are neurohypophysial hormones which share a high sequence and structure homology. These are two cyclic C-terminally amidated nonapeptides with different residues at position 3 and 8. In mammals, AVP and OT exert their multiple biological functions through a specific G protein-coupled receptor family: four receptors are identified, the V1a, V1b, V2 receptors (V1aR, V1bR and V2R) and the OT receptor (OTR). The chemical structure of AVP and OT was elucidated in the early 1950s. Thanks to X-ray crystallography and cryo-electron microscopy, it took however 70 additional years to determine the three-dimensional structures of the OTR and the V2R in complex with their natural agonist ligands and with different signaling partners, G proteins and β-arrestins. Today, the comparison of the different AVP/OT receptor structures gives structural insights into their orthosteric ligand binding pocket, their molecular mechanisms of activation, and their interfaces with canonical Gs, Gq and β-arrestin proteins. It also paves the way to future rational drug design and therapeutic compound development. Indeed, agonist, antagonist, biased agonist, or pharmacological chaperone analogues of AVP and OT are promising candidates to regulate different physiological functions and treat several pathologies.

Glucocorticoids are members of steroid hormones that are biosynthesized in the intermediate cellular zone of the adrenal cortex (zona fasciculata) and released into the peripheral blood as final products of the hypothalamic-pituitary-adrenal (HPA) axis, as well as under the control of the circadian biologic system. These molecules regulate every physiologic function of the organism as they bind to an almost ubiquitous hormone-activated transcription factor, the glucocorticoid receptor (GR), which influences the rate of transcription of a huge number of target genes amounting to up to 20% of the mammalian genome. The evolving progress of cellular, molecular and computational-structural biology and the implication of epigenetics in every-day clinical practice have enabled us a deeper and ever-increasing understanding of how target tissues respond to natural and synthetic glucocorticoids. In this chapter, we summarize the current knowledge on the structure, expression, function and signaling of the human glucocorticoid receptor in normal and pathologic conditions.

The Androgen Receptor (AR) is a ligand (androgen) activated transcription factor and a member of the nuclear receptor (NR) superfamily. It is required for male sex hormone function. AR-FL (full-length) has the domain structure of NRs, an N-terminal domain (NTD) required for transactivation, a DNA-binding domain (DBD), a nuclear localization signal (NLS) and a ligand-binding domain (LBD). Paradoxes exist in that endogenous ligands testosterone (T) and 5α-dihydrotestosterone (DHT) have differential effects on male sexual development while binding to the same receptor and transcriptional specificity is achieved even though the androgen response elements (AREs) are identical to those seen for the progesterone, glucocorticoid and mineralocorticoid receptors. A high resolution 3-dimensional structure of AR-FL by either cryo-EM or X-ray crystallography has remained elusive largely due to the intrinsic disorder of the NTD. AR function is regulated by post-translational modification leading to a large number of proteoforms. The interaction of these proteoforms in multiprotein complexes with co-activators and co-repressors driven by interdomain coupling mediates the AR transcriptional output. The AR is a drug target for selective androgen receptor modulators (SARMS) that either have anabolic or androgenic effects. Protstate cancer is treated with androgen deprivation therapy or by the use of AR antagonists that bind to the LBD. Drug resistance occurs due to adaptive AR upregulation and the appearance of splice variants that lack the LBD and become constitutively active. Bipolar T treatment and NTD-antagonists could surmount these resistance mechanisms, respectively. These recent advances in AR signaling are described.