Steroid hormone

Steroid hormones are steroids that act as hormones. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens. Vitamin D derivatives are a sixth closely-related hormone system with homologous receptors, though technically sterols rather than steroids.

Synthesis

Steroidogenesis with enzymes and intermediates

The natural steroid hormones are generally synthesized from cholesterol in the gonads and adrenal glands. These forms of hormones are lipids. They can pass through the cell membrane as they are fat-soluble, and then quite easily combine with a protein receptor which may be nuclear or cytosolic depending on the steroid hormone, to bring about changes within the cell. Steroid hormones are generally carried in the blood bound to specific carrier proteins such as sex hormone-binding globulin or corticosteroid-binding globulin. Further conversions and catabolism occurs in the liver, in other "peripheral" tissues, and in the target tissues.

Synthetic steroids and sterols

A variety of synthetic steroids and sterols have also been contrived. Most are steroids, but some non-steroidal molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker, and some much stronger, than the natural steroids whose receptors they activate.

Some examples of synthetic steroid hormones:

• Glucocorticoids: prednisone, dexamethasone, triamcinolone
• Mineralocorticoid: fludrocortisone
• Vitamin D: dihydrotachysterol
• Androgens: oxandrolone, nandrolone (also known as anabolic steroids)
• Estrogens: diethylstilbestrol (DES)
• Progestins: norethindrone, medroxyprogesterone acetate

Effects

Steroids exert a wide variety of effects mediated by slow genomic as well as by rapid nongenomic mechanisms. They bind to nuclear receptors in the cell nucleus for genomic actions. Membrane-associated steroid receptors activate intracellular signaling cascades involved in nongenomic actions.

Because steroids and sterols are lipid-soluble, they can diffuse fairly freely from the blood through the cell membrane and into the cytoplasm of target cells. In the cytoplasm, the steroid may or may not undergo an enzyme-mediated alteration such as reduction, hydroxylation, or aromatization. In the cytoplasm, the steroid binds to the specific receptor, a large metalloprotein. Upon steroid binding, many kinds of steroid receptor dimerize: Two receptor subunits join together to form one functional DNA-binding unit that can enter the cell nucleus. In some of the hormone systems known, the receptor is associated with a heat shock protein, which is released on the binding of the ligand, the hormone. Once in the nucleus, the steroid-receptor ligand complex binds to specific DNA sequences and induces transcription of its target genes.

References

1. Brook CG. Mechanism of puberty. Horm Res. 1999;51 Suppl 3:52-4. Review.PMID: 10592444
2. Holmes SJ, Shalet SM. Role of growth hormone and sex steroids in achieving and maintaining normal bone mass. Horm Res. 1996;45(1-2):86-93. Review. PMID: 8742125
3. Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, Forabosco A, Schlessinger D. Determination and stability of sex. Bioessays. 2007 Jan;29(1):15-25. Review. PMID: 17187356
4. Couse JF, Korach KS. Exploring the role of sex steroids through studies of receptor deficient mice. J Mol Med. 1998 Jun;76(7):497-511. Review. PMID: 9660168
5. McEwen BS. Steroid hormones: effect on brain development and function. Horm Res. 1992;37 Suppl 3:1-10. Review. PMID: 1330863

Further Reading

Simons SS Jr. What goes on behind closed doors: physiological versus pharmacological steroid hormone actions. Bioessays. 2008 Aug;30(8):744-56. PMID: 18623071

External links

• Steroid Hormone Action (a Flash Animation)
• Steroidogenic enzymes: Review on structure, function, and role in regulation of steroid hormone biosynthesis
• [1] An animated and narrated tutorial about nuclear receptor signaling.