Steroid Hormones Receptor Biochemistry

Steroid receptors are highly specific macromolecules found in central regulatory organs (e.g., pituitary, hypothalamus), in various end-point target tissues (e.g., uterus, vagina, prostate), and in lower concentrations in the brain, liver, kidney, ovary, and many other organs. Steroid hormones exhibit remarkable tissue selectivity when binding to these 

While the macromolecules and target tissues involved show extreme specificity for the appropriate steroid hormones and their congeners, the general scheme of the steroid-receptor mechanism is remarkably uniform. We can therefore deal with this receptor model in a general way, mentioning specific details as appropriate in the subsections of this chapter. 

The general steroid-receptor hypothesis is based mainly on estrogen and progesterone receptors. The currently accepted mechanism is unique and consists of several steps at different subcellular structures  

Upon entering the cell, the steroid molecule initially binds to the steroid receptor protein (E domain) to form the steroid-hormone-receptor complex. This complex concomitantly binds to an additional eight or more other peptides (also via the E domain) these peptides are termed chaperone peptides and consist of macromolecules such as heat shock proteins (e.g., hsp70, hsp90). The chaperone peptides help to twist and turn the steroid receptor protein into an improved three-dimensional shape for final and optimal binding of the steroid molecule. Following binding of the chaperone peptides, the steroid-hormone-receptor complex becomes a mature steroid-hormone-receptor 

The steroid-receptor complex remains in the nucleus for a limited time only, and eventually dissociates from the chromatin. About 40% of the receptors released in this dissociation are recycled and used again the rest are destroyed and resynthesized. Steroid hormones can even regulate the level of synthesis of their own receptors, and sometimes the synthesis of other steroid receptors as well. 

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Gehring, U., Steroid hormone receptors Biochemistry, genetics and molecular biology. Trends Biochem. Sci. 12 399-402, 1987. 

Gehring, U. (1987). Steroid Hormone Receptors Biochemistry, Genetics, and Molecular Biology, Elsevier Publications, Cambridge. 

Peroxisome Proliferator-Activated Receptor (PPAR), chemistry of Steroid Hormones, Biology and Biochemistry of... 

Marimuthu, A. et al. (2002) Design of thyroid hormone receptor antagonists from first principles. Journal of Steroid Biochemistry and Molecular Biology, 83, 59-73. 

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