How Hormones Work

Intracellular Hormone Receptors

Lipid-derived (soluble) hormones such as steroid hormones diffuse across the membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream. At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of cells. The steroid hormones pass through the plasma membrane of a target cell and adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes on the cell's DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes. This, in turn, determines the amount of corresponding protein that is synthesized by altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. In this way, the steroid hormone regulates specific cell processes as illustrated in Figure.

Art Connection

Illustration shows a hormone crossing the cellular membrane and attaching to the NR/HSP complex. The complex dissociates, releasing the heat shock protein and a NR/hormone complex. The complex dimerizes, enters the nucleus, and attaches to an HRE element on DNA, triggering transcription of certain genes.
An intracellular nuclear receptor (NR) is located in the cytoplasm bound to a heat shock protein (HSP). Upon hormone binding, the receptor dissociates from the heat shock protein and translocates to the nucleus. In the nucleus, the hormone-receptor complex binds to a DNA sequence called a hormone response element (HRE), which triggers gene transcription and translation. The corresponding protein product can then mediate changes in cell function.

Heat shock proteins (HSP) are so named because they help refold misfolded proteins. In response to increased temperature (a “heat shock”), heat shock proteins are activated by release from the NR/HSP complex. At the same time, transcription of HSP genes is activated. Why do you think the cell responds to a heat shock by increasing the activity of proteins that help refold misfolded proteins?

Other lipid-soluble hormones that are not steroid hormones, such as vitamin D and thyroxine, have receptors located in the nucleus. The hormones diffuse across both the plasma membrane and the nuclear envelope, then bind to receptors in the nucleus. The hormone-receptor complex stimulates transcription of specific genes.

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