Laws and Penalties: Concerns over growing illegal AAS abuse by teenagers, and many of the just discussed long-term effects, led Congress in 1991 to place the whole AAS class of drugs into Schedule III of the Controlled Substances Act (CSA). Under this legislation, AAS are defined as any drug or hormonal substance, chemically and pharmacologically related to T (other than estrogens, progestins, and corticosteroids) that promotes muscle growth. The possession or sale of AAS without a valid prescription is illegal. Since 1991, simple possession of illegally obtained AAS carry a maximum penalty of one year in prison and a minimum $1,000 fine if this is an individual’s first drug offense. The maximum penalty for trafficking (selling or possessing enough to be suspected of selling) is five years in prison and a fine of $250,000 if this is the individual’s first felony drug offense. If this is the second felony drug offense, the maximum period of imprisonment and the maximum fine both double. While the above listed penalties are for federal offenses, individual states have also implemented fines and penalties for illegal use of AAS. State executive offices have also recognized the seriousness of AAS abuse and other drugs of abuse in schools. For example, the State of Virginia enacted a law that will allow student drug testing as a legitimate school drug prevention program (48, 49).
The C-terminal AF-2 transactivation domain is highly conserved within the nuclear receptor superfamily 31 and is recognized by various transcriptional coactivators. 32 , 33 AF-2 is localized to the most C-terminal end of the E domain. A third transactivation domain called AF-2a or tau2 has been localized to the N-terminal region of the LBD of ERα 31 and GR. 34 Deletion experiments revealed a role for AF-2a and the DBD in targeting rat GR to the nuclear matrix, 35 an interconnected ribonuclear-protein network within the nucleus that is thought to play an important roles in transcription of active genes by stabilizing the assembly of the transcriptional machinery. 36
Likewise, a novel isoform of ERβ, termed ERβ2, containing an in-frame insertion of an exon of 54 nucleotides, resulting in an insertion of 18 amino acids in the LBD, was recently identified first by screening rat prostate cDNA library, and is also expressed in human cell lines. 43 ERβ2 binds E 2 with lower affinity (Kd = 8 nM) than ERβ1 (Kd = 1 nM). At least 10 splice variants of ERβ have been identified. 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55