The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals

Because steroids are lipophilic, they diffuse easily through the cell membranes, and therefore have a very large distribution volume. In their target tissues, steroids are concentrated by an uptake mechanism which relies on their binding to intracellular proteins (or " receptors ", see below). High concentration of steroids are also found in adipose tissue, although this is not a target for hormone action. In the human male, adipose tissue contains aromatase activity, and seems to be the main source of androgen-derived estrogens found in the circulation. But most of the peripheral metabolism occurs in the liver and to some extent in the kidneys, which are the major sites of hormone inactivation and elimination, or catabolism (see below).

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).

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. This is in contrast to the actions of non-steroid hormones, which are water-soluble typically peptide hormones, acting through membrane bound receptors and intracellular second messenger systems to exert their effects. 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 . [2] [6] [7] [8]

The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals

the steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals

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