Hormonal Regulation

Regardless of the distance across which a hormone acts, only those cells that contain a specific receptor can respond to the corresponding hormonal signal. The expression of receptors only in the target cells ensures that these (and only these) cells respond in the appropriate way to the hormone, despite the possible presence of a large number of other hormones in the immediate surroundings.

In addition to the distance across which they act, hormones may be further divided into two large groups based on where in the target cell the hormone receptors are located. The first class consists of extracellular hormones that act via specific cell-surface receptors. Most hormones of this family are proteins (such as insulin, interferons, interleukins, and growth factors), fatty acid derivatives (such as prostaglandins and leukotrienes), or amino acid derivatives (such as serotonin and melatonin).

Extracellular hormones bind to specific receptors on the cell surface, triggering a chain of events inside the cell. These events may include the modification (e.g., phosphorylation or dephosphorylation) of one or more "second messengers"—small molecules that act inside the cell to continue the signaling cascade. In addition to any other short-term effects they may have, virtually all hormonal signaling processes culminate in a change in the expression of a set of target genes. Depending on the cell, the transcription of these genes may be increased or decreased, or be turned completely on or turned off, in response to the presence of the hormone.

The other major class of hormonal signals consists of small, typically fat-soluble molecules that are able to diffuse freely into cells. Once inside the cell, the hormone binds to its receptor to directly regulate the expression of target genes. The hormone-receptor complex is a functional transcription factor that in most cases leads to the expression of its target genes. This modulation primarily occurs directly, via binding of the hormone-receptor complex to target DNA sequences, although additional regulation can occur indirectly, via interaction with other transcription factors.

Since the vast majority of these receptors are always in the nucleus, the family is referred to as the "nuclear hormone receptor superfamily." It is also often also called the "steroid receptor superfamily," because steroid receptors were the first of this family to be identified. Steroid hormones include testosterone, progesterone, and the estrogens. The discussion that follows will focus on hormones that interact with nuclear receptors to directly influence gene expression.