AN INSIGHT INTO THE MOLECULAR MECHANISMS OF STEROIDS

Jason Seewoodhary

Abstract


Steroid hormones are derived from a cholesterol precursor. They are secreted directly into the blood where they are bound to carrier proteins, which transport them to target cells. Due to their lipophilic nature they traverse cell membranes by simple diffusion and bind to Steroid Hormone Receptors (SHR’s).

The mechanism of action of SHR’s can be either genomic or non-genomic; this summary will hone in on how activation of SHR’s regulates gene expression. 

SHR’s are ligand-activated proteins that function as transcription factors, which direct and facilitate the transcription of DNA by RNA Polymerase II. They are located predominantly within the cytosol or nucleus of target cells. SHR’s have a central DNA binding domain (DBD), which via zinc finger and ‘P’ box motifs, targets the receptor to Hormone Response Elements (HRE’s).HRE’s are short sequences of DNA within the promoter region that conveys direct transcriptional responsiveness to genes. SHR’s also have a ligand binding domain (LBD), which acts as a molecular switch to turn on transcriptional activity when a hormonal ligand induces a conformational change in the receptor. Transactivation domains 1 and 2 (AF-1 and AF-2) are located close to the DBD and LBD respectively and upon hormone binding act synergistically to activate the SHR. The structure of a SHR is illustrated in figure 1 below (Beato M et al., 2000).


Keywords


Steroids; Steroid Hormone Receptor; Co-Activator; Co-Repressor; Transcription Factor

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References


Beato M, Klug J. Steroid hormone receptors: an update. Human Reproduction Update6 (2000): pp225-236.

Henttu PM, Kalkhoven E et al. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Mol. Cell. Biol. 17 (1997): pp1832-1839.

Jeong KW, Lee YH et al. Recruitment of the SWI/SNF chromatin remodelling complex to steroid hormone-regulated promoters by nuclear receptor coactivator flightless-1. J Biol. Chem.284 (2009): pp29298-309.

Lanz RB, McKenna NJ et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97 (1999): pp17-27.

Lavery DN, McEwan IJ. Structure and function of steroid receptor AF1 transactivation domains: induction of active conformations. Biochem J 391 (2005): pp449-464.

McKay LI, Cidlowski JA. Cross-talk between Nuclear Factor-κB and the Steroid Hormone Receptors: Mechanisms of Mutual Antagonism. Molecular Endocrinology12 (1998): pp45-56.

Nola M, Jukic S et al. Effects of tamoxifen on steroid hormone receptors and hormone concentrations and the results of DNA analysis by flow cytometry in endometrial carcinoma. Gynecol Oncol. 72 (1999): pp331-6.

Shank LC, Paschal BM. Nuclear transport of steroid hormone receptors. Critical reviews in eukaryotic geneexpression15 (2005): pp49-73.

Weigel NL. Steroid hormone receptors and their regulation by phosphorylation. Biochem J319 (1996): pp657-667.

Weigel NL, Zhang Y. Ligand-independent activation of steroid hormone receptors. J Mol. Med.76 (1998): pp469-79.


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