Lipid-soluble hormones diffuse across the plasma membrane of cells, binding to receptors inside the cells where they alter gene expression.
- Describe how hormones alter cellular activity by binding to intracellular receptors
- Lipid -soluble hormones are able to diffuse directly across the membranes of both the endocrine cell where they are produced and that of the target cell, as the cell membranes are made of a lipid bilayer.
- These hormones can bind to receptors that are located either in the cytoplasm of the cell or within the nucleus of the cell.
- When these hormones bind to their receptors, this signals the cell to synthesize more or less mRNA from a gene or genes, which then results in more or less protein being created from those mRNA molecules.
- The increase or decrease in protein production can alter the cell structurally or alter how and when it catalyzes chemical reactions.
- gene expression: the transcription and translation of a gene into messenger RNA and, thus, into a protein
- transcription: the synthesis of RNA under the direction of DNA
- steroid: a class of organic compounds having a structure of 17 carbon atoms arranged in four rings; they are lipids, and occur naturally as sterols, bile acids, adrenal and sex hormones, and some vitamins
Intracellular Hormone Receptors
Lipid-derived (soluble) hormones such as steroid hormones diffuse across the lipid bilayer 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 the target cells. They then adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes within the cell’s DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules from specific genes. This, in turn, determines the amount of corresponding protein that is synthesized from this RNA; this is known as 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.
Hormone regulation of gene expression: 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.
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 in the same way that steroid hormones do. For example, the active vitamin D metabolite, calcitriol, mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins that are involved in calcium absorption in the intestine. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood and to the maintenance of bone content.