Journal ArticleDOI
Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated
TLDR
The presence of the enzyme 11 beta-hydroxy-steroid dehydrogenase, which converts cortisol and corticosterone, but not aldosterone, to their 11-keto analogs, means that these analogs cannot bind to mineralocorticoid receptors.Abstract:
Mineralocorticoid receptors, both when in tissue extracts and when recombinant-derived, have equal affinity for the physiological mineralocorticoid aldosterone and for the glucocorticoids cortisol and corticosterone, which circulate at much higher concentrations than aldosterone. Such receptors are found in physiological mineralocorticoid target tissues (kidney, parotid, and colon) and in nontarget tissues such as hippocampus and heart. In mineralocorticoid target tissues the receptors are selective for aldosterone in vivo because of the presence of the enzyme 11 beta-hydroxy-steroid dehydrogenase, which converts cortisol and corticosterone, but not aldosterone, to their 11-keto analogs. These analogs cannot bind to mineralocorticoid receptors.read more
Citations
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Journal ArticleDOI
Brain corticosteroid receptor balance in health and disease.
TL;DR: The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation and Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals.
Journal ArticleDOI
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
TL;DR: Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.
Journal ArticleDOI
Molecular Mechanisms of Human Hypertension
TL;DR: Supported in part by a Specialized Center of Research in Hypertension and NIH K08 awards (to A. G. and D. S. G.) and a grant from the Howard Hughes Medical Institute.
Journal ArticleDOI
Reproduction and resistance to stress: When and how
TL;DR: Four mechanisms underlying resistance of the gonadal axis to stress are suggested, likely genetically determined, and their expression may depend upon a complex interaction with environmental factors.
Journal ArticleDOI
Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation
Tim J Cole,Julie A. Blendy,A.P. Monaghan,K. Krieglstein,Wolfgang Schmid,Adriano Aguzzi,Giamila Fantuzzi,E. Hummler,K Unsicker,G. Schutz +9 more
TL;DR: The results suggest that the adrenal medulla may be formed from two different cell populations: adrenergic-specific cells that require glucocorticoids for proliferation and/or survival, and a smaller noradrenergic population that differentiates normally in the absence of glucOCorticoid signaling.
References
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Journal ArticleDOI
The steroid and thyroid hormone receptor superfamily
TL;DR: A superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid is identified, suggesting mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
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Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor
Jeffrey L. Arriza,Jeffrey L. Arriza,Cary Weinberger,Gail M. Cerelli,Thomas M Glaser,Barbara Handelin,David E. Housman,Ronald M. Evans +7 more
TL;DR: Together the hMR and hGR provide unexpected functional diversity in which hormone-binding properties, target gene interactions, and patterns of tissue-specific expression may be used in a combinatorial fashion to achieve complex physiologic control.
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Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age
TL;DR: It is suggested that in both conditions there is a defect in the renal conversion of cortisol to cortisone by 11 beta-OHSD which results in high intrarenal cortisol levels, acting on type 1 mineralocorticoid receptors to cause sodium retention.
Journal ArticleDOI
Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity
TL;DR: It is suggested that hippocampal [3H]corticosterone-binding sites and renal MR may have identical intrinsic specificity for steroids, with apparent specificity differences the result of tissue-specific sequestration of naturally occurring steroids other than Aldo.
Journal ArticleDOI
The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone.
TL;DR: Two specificity—conferring mechanisms are described which are posited to allow aldosterone occupancy of its appropriate receptor in target tissues.