O Steroid Hormone Receptors

Steroid hormones regulate tissue-specific gene expression. The individual hormones exhibit remarkable tissue selectivity, even though their structural differences are relatively minor. Estrogens such as estradiol increase uterine cell proliferation, for example, but not prostate cell proliferation. Androgens such as testosterone do the reverse, but neither androgens nor estrogens affect stomach epithelium. The

Figure 25.6 • Common steroid modifications to alter therapeutic utility. (*, prodrug.)

Androstenedione (Reduced activity relative to testosterone)

Figure 25.6 • Common steroid modifications to alter therapeutic utility. (*, prodrug.)

basis for this selectivity is the presence of selective steroid hormone receptors in individual tissues. This section provides an overview of steroid hormone receptors and their mode of action.1,2

The steroid receptors themselves are key players in gene expression, but many other proteins are involved in this process. Chaperone proteins, for example, help fold the receptor proteins into the proper three-dimensional shape for binding the steroid ligand. Together, the steroid hormone receptor and associated proteins (Fig. 25.7; details on next page) make up the mature-receptor complex. Transcription (or repression of transcription) occurs when all the necessary associated proteins have been recruited to the DNA-receptor complex. In addition to the major effects on transcription, some effects of steroid hormones are mediated via rapid, nongenomic mech-

Steroid Hormone

Steroid Hormone anisms. Some of these actions appear to involve classical steroid hormone receptors, whereas others rely on novel membrane receptors.7-9 This is an active area of study and will help explain all the various actions of steroid hormones.

Structure of Steroid Hormone Receptors

The complementary DNAs (cDNAs) of all the major steroid hormone receptors have been cloned, giving the complete amino acid sequence of each. Although the whole three-dimensional structure of a steroid hormone receptor has not been solved (structures of the ligand-binding domains of the steroid hormone receptors have been elucidated; see next page in this section), the functional role of each part is well known (see Fig. 25.8).10 The organization of the domains for all types of steroid hormone receptors is the same, but the number of amino acids for each receptor varies:

1. N-terminal (A/B) domain. Once the steroid-receptor complex has bound to the target gene(s), this domain (also called the A/B modulator domain) activates the hormone response elements adjacent to the genes. The hormone response elements are on the DNA adjacent to the target gene. They contain about 12 to 18 base-pair DNA sequences and consist of two "half sites" that are separated by a variable spacer. In the nucleus, steroid hormone-receptor

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment