Cell surface receptor interactions of C27-steroid hormone ecdysterone immobilized on nanodispersed magnetite
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Ecdysterone
Steroid hormone
ENDOCRINE DISRUPTING CHEMICALS ALTER STEROID TRANSPORT PROTEINS AND STEROID FREE AND BOUND FRACTIONS
The effects of endocrine disrupting chemicals (EDCs) on the development of sexually dimorphic characteristics in vertebrates have been studied extensively for over sixty years. Throughout this time , studies have focused mainly on the disrupted steroidogenesis and steroid signaling pathways. Often , only freely suspended plasma steroids were reported , despite the fact that a large portion of plasma steroids are bound to circulating steroid transport proteins. When bound to transport proteins , steroids have reduced binding to steroid nuclear and membrane receptors and increased binding to transport protein receptors. Thus , steroid transport proteins regulate steroid activity. Sexually dimorphic characteristics of tissues require specific concentrations and milieus of steroids during development and disruption of these steroid milieus leads to abnormal differentiation. Therefore , it is likely that the developing organism also requires specific free and bound ratios depending on the sex. However , few studies have addressed the effects of EDCs on sexual dimorphism of steroid transport proteins and steroid fractions despite the impact that transport proteins have on steroid signaling , development , and physiology. To address this , I first summarize the current literature on the regulation of transport proteins , their interactions with steroid signaling , and how transport proteins are affected by environmental contaminates. These findings are culminated into a new model of steroid signaling that includes transport protein mediated pathways. Second , using HPLC-MS/MS , I show that a normal sexual dimorphism exists in free and bound steroid ratios for the steroids progesterone , corticosterone , testosterone , and 17[beta]-estradiol. Additionally , I found a normal sexual dimorphism in the ratio of the bound precursor progesterone , to its potent metabolites , with females having higher progesterone to metabolite ratios than those in males. When exposed to the model EDC , Vinclozolin , sexual dimorphism of free and bound steroids was lost , with males and females responding to disruption in different ways. The disruption of plasma steroid ratios was found in the absence of changes to liver steroid transport protein concentrations. The results of this study show that steroid free and bound ratios as well as ratios of precursor to metabolite steroids can be altered by EDCs. This study clearly shows that future work in determining effects of EDC should also determine free and bound fractions of steroids to better understand effects of contaminants.
Sex steroid
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Sexual dimorphism
Sexual Differentiation
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Advances in technology have allowed for the sensitive, specific, and simultaneous quantitative profiling of steroid precursors, bioactive steroids and inactive metabolites, facilitating comprehensive characterization of the serum and urine steroid metabolomes. The quantification of steroid panels is therefore gaining favor over quantification of single marker metabolites in the clinical and research laboratories. However, although the biochemical pathways for the biosynthesis and metabolism of steroid hormones are now well defined, a gulf still exists between this knowledge and its application to the measured steroid profiles. In this review, we present an overview of steroid hormone biosynthesis and metabolism by the liver and peripheral tissues, specifically highlighting the pathways linking and differentiating the serum and urine steroid metabolomes. A brief overview of the methodology used in steroid profiling is also provided.
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Steroid biosynthesis
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Treatment of newborn rats with a single low dose of dexamethasone gave rise to lasting alteration of thymocytic receptor binding capacity. The receptors decreased markedly in number, while their affinity for the hormone was slightly increased. It appears that imprinting with a steroid changes the receptor--hormone relationship in the adult organism.
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The cellular steroid receptors, such as the prostate androgen receptor, can be characterized by a method in which steroid antibodies are used to eliminate nonspecific and non-receptor binding of the steroid hormones. with steroid antibody coupled to Sepharose, the method provides a simple and rapid way of assaying steroid receptors.
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Steroidal hormones produced by humans and animals are constantly excreted into the environment in their active forms. The primary steroid hormones are progesterone, estrone, estradiol, testosterone, and cortisol, all of which are lipophilic and poorly soluble in water. The steroids of major concern are estrone and estradiol-17Ī², since they exert their physiological effects at a lower concentration than other steroids and can be found in the environment in concentrations above their LOEL for fish and plants (10 ng/l). The steroid hormones can be readily measured in run-off, soil, and groundwater, but each steroid has its distinct pathway of transport. Since the major source of steroids in the environment appears to be cattle and chickens, the hormonal steroid input into the environment could be drastically reduced by well-established techniques such as buffer strips and composting.
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