Corticosteroid Receptors: an overview

The intracellular receptors for the GCs and mineralocorticoids, the GRs and MRs, respectively, were identified during the 1960s and cloned in the 1980s. GRs were characterized by their presence in GC target cells and their ability to specifically bind radioactively labeled cortisol and related GCs. MRs were characterized in mineralocorticoid target tissues by their ability to bind labeled aldosterone. Cortisol and corticosterone, the natural GCs, bind to GRs with dissociation constants in the range of normal GC concentrations in the blood. Similarly, aldosterone binds to MRs with a dissociation constant in the range of normal aldosterone concentrations in the blood, which are 100–1000 times lower than GC concentrations.

In the late 1980s, cortisol and corticosterone were found to bind to MRs with almost the same dissociation constant as aldosterone, that is, with a much higher affinity than to GRs. That posed a major quandary because GCs would normally be expected to flood mineralocorticoid target cells and saturate MR binding sites, how does aldosterone bind to MRs? The quandary was resolved with the identification in mineralocorticoid target cells of the enzyme 11β-HSD2, which protects the MRs by rapidly inactivating GCs to their 11-keto forms, allowing aldosterone access to MRs. MRs in certain cells are unprotected by 11β-HSD2 and respond to GCs at concentrations far lower than those required to activate the GRs. Some cells in male and female reproductive tracts have 11β-HSD2 that may protect them from excessive levels of GCs.

The role of MRs as mediators of GC actions has been studied most extensively in the central nervous system. Both GRs and MRs are found in the brain and spinal cord, MRs being particularly abundant in the dentate gyrus and pyramidal cells of the hippocampus as well as other regions of the limbic system. There appears to be no 11β-HSD2 in the hippocampus, so hippocampal MRs are bound and activated mainly by GCs. Only the MRs in the anterior hypothalamus and circumventricular organs are protected by 11β-HSD2 and are therefore controlled by aldosterone. GRs are more widely dispersed in the central nervous system than MRs and are present in both neurons and glial cells.

GRs and MRs, when activated by hormone binding, initiate hormone actions by translocating to the nucleus and activating or repressing particular genes. Most GC and mineralocorticoid actions are thought to be produced through such genomic mechanisms, which are relatively slow, usually taking hours to become manifest. There is mounting evidence, however, that certain rapid effects of these and other steroid hormones, particularly in the nervous system, may be mediated by non-genomic effects transmitted through membrane receptors.

Endocrinology and Metabolism: Open Access is a peer reviewed journal which focuses on the publication of current research and developments on the endocrine glands and its secretions with their coordination with metabolism and reproduction.

Endocrinology and Metabolism: Open Access Journal is using Editorial Tracking System to maintain quality and transparency to the author in the peer-review process. Review processing will be performed by the editorial board members of the Journal Endocrinology and Metabolism: Open Access or by Reviewers (outside experts in the field). Two independent reviewer’s approval (Minimum reviewer’s approval) followed by editor approval is obligatory for acceptance of any manuscript excluding an editorial.

Journal is now accepting manuscripts for volume 5 for year 2021. We publish minimum of 5 and maximum of 20 articles per issue every month. Submissions to our journal are given high priority during the process.

Submit your manuscript at:

https://www.imedpub.com/submissions/endocrinology-metabolism-open-access.html 

You may also send the manuscript as an attachment to mail endometabol@emedscholar.com

Media Contact
Eliza Grace
Associate Managing Editor
Endocrinology and Metabolism: Open Access
E-Mail: endometabol@emedscholar.com