Steroids and Athletes: Genes Work Overtime 0/8
Steroids Alter Genetic Function?
Once inside the nucleus, the steroid-receptor complex binds to specific areas within the DNA (regulatory sites) to induce gene transcription1, which directs the synthesis of specific proteins (Figure 5). A brief review of protein synthesis follows so we can understand how this happens.
DNA (deoxyribonucleic acid) is a large molecule containing the genes that code instructions for the synthesis of proteins. The code consists of a sequence of repeating subunits, or nucleotides2. Each nucleotide has three parts: 1) a phosphate group (an acid), 2) a sugar (in the case of DNA, deoxyribose), and 3) a ring of carbon and nitrogen atoms (the nitrogen can form a bond with hydrogen so the nucleotide is basic) (Figure 6). A chain of nucleotides (nucleic acids3) is formed by linking the phosphate group of one nucleotide to the sugar of an adjacent nucleotide. The bases stick out from the side of the phosphate-sugar backbone. The 3rd component described above, the base consisting of a ring of carbon and nitrogen atoms, occurs in 4 forms for DNA. These bases can be divided into two classes: the purine bases4 (adenine and guanine), which have double rings of nitrogen and carbon atoms, and the pyrimidine bases5 (cytosine and thymine), which have only a single ring. A molecule of DNA consists of two polynucleotide chains coiled around each other in the form of a double helix (Figure 6). The chains are held together by hydrogen bonds6 (see Module 5) between purine and pyrimidine bases – specifically, adenine is paired with thymine and guanine is paired with cytosine. Thus, one chain in the double helix is complementary to the other.
DNA is “read” by using three-base sequences to form “words” that direct the production of specific amino acids. These three-base sequences, known as triplets, are arranged in a linear sequence along the DNA. Each triplet codes for the synthesis of an amino acid and the specific chain of amino acids builds a specific protein. Most of the DNA is contained in the nucleus of the cell (a small amount is in the mitochondria), yet most protein synthesis occurs in the cytoplasm of the cell. Since DNA molecules are too large to pass through the nuclear membrane into the cytoplasm, a message must carry the genetic information from the nucleus into the cytoplasm. This message is carried by messenger RNA7 (mRNA; ribonucleic acid) molecules (Figure 5). The passage of information from DNA to mRNA in the nucleus is called transcription because the DNA sequence is actually transcribed into a corresponding RNA sequence. Once the mRNA passes through the nuclear membrane into the cytoplasm, it directs the assembly of a specific sequence of amino acids to form a protein – this process is translation8 (Figure 5). This occurs on ribosomes9 or in the rough endoplasmic reticulum (not shown in the figure). Thus, the synthesis of a protein is governed by the information in the DNA – mRNA simply serves as the messenger (and thus its name)! In the case of anabolic steroids10, the steroid-receptor complex induces genes to make specific proteins within muscle cells that help them to become larger and more powerful (discussed below). However, increased muscle growth is not the only action of anabolic steroids. Like testosterone, anabolic steroids can stimulate chest hair growth and cause acne and emotional problems (i.e., depression and hostility). The ability of anabolic steroids to produce these side effects is due to the cell type in which the steroid receptors11 are found and the specific DNA sequence that is transcribed. Thus, androgen12receptors must be plentiful in cells of chest hair follicles13 (see Module 2), in secretory cells of sebaceous glands, and on neurons within the limbic system (important in mood) of the brain.
1 the passage of information from DNA to mRNA in the nucleus; this is directed by several enzymes.
2 the hydrolysis product of nucleic acids comprising 3 parts: 1) a phosphate group (an acid), 2) a sugar (deoxyribose for DNA and ribose for RNA), and 3) a ring of carbon and nitrogen atoms (nucleosides; purines and pyrimidines).
3 a chain of repeating subunits of nucleotides.
4 a type of nucleotide present in DNA that consists of double rings of carbon and nitrogen atoms. The two purine bases present in DNA are adenine and guanine.
5 a type of nucleotide present in DNA that consists of a single ring of carbon and nitrogen atoms. The two pyrimidine bases present in DNA are cytosine and thymine.
6 occurs between two strongly negatively charged ions. A type of Van der Waals force. When several occur simultaneously, they are responsible for increasing the stability of a drug-receptor interaction.
7 also known as mRNA or ribonucleic acid; it is transcribed from DNA and moves to the cytoplasm to direct protein synthesis.
8 the process of assembling a specific sequence of amino acids (based on the instructional code provided by mRNA) to form a protein. It occurs in the cytoplasm on ribosomes or in the rough endoplasmic reticulum.
9 structures within the cytoplasm consisting of proteins and a different form of RNA (rRNA) that support the process of protein translation
10 synthetic versions of testosterone designed to promote muscle growth without producing androgenic effects. The better term is anabolic-androgenic steroid.
11 a protein to which hormones, neurotransmitters and drugs bind. They are usually located on cell membranes and elicit a function once bound.
12 a steroid hormone such as testosterone that is masculinizing (deepens voice, produces facial & chest hair, sperm production
13 a small sac; hair follicles are internalized structures of epithelial cells in which the hair is synthesized and grows
Figure 5 Testosterone (or anabolic-androgenic steroids) binds to the androgen receptor in the cytoplasm and the complex moves into the nucleus where it interacts with DNA to initiate protein synthesis.
Figure 6 Nucleotides are joined together in a chain (PO^4- groups of one nucleotide are linked with the sugar moiety of an adjacent nucleotide). Bases in one chain bind to complementary bases in another chain to form a double helix.