C2.1.12 Intracellular receptors that affect gene expression Notes

Intracellular Receptors Regulate Gene Expression by Activating Target Genes

1. Some signaling molecules, such as steroid hormones, are hydrophobic and can pass through the plasma membrane of a cell.
2. These molecules bind to intracellular receptors, which are typically located in the cytoplasm or nucleus.
3. Upon binding, these receptors become activated and directly influence gene expression by interacting with specific DNA sequences, leading to the transcription of certain genes.

How Do Intracellular Receptors Work?

Hormone Entry

1. Steroid hormones, such as oestradiol, progesterone, and testosterone, are hydrophobic.
2. This allows them to diffuse through the plasma membrane and enter the cell.

Binding to Receptor

1. Once inside, the hormone binds to a specific intracellular receptor in the cytoplasm or nucleus.
2. This binding activates the receptor, changing its shape to expose a DNA-binding domain.

Formation of Hormone-Receptor Complex

1. The activated receptor and hormone form a hormone-receptor complex.
2. This complex acts as a transcription factor, a molecule that can bind to DNA and influence gene expression.

DNA Binding and Gene Activation

1. The hormone-receptor complex moves into the nucleus (if it isn’t already there) and binds to specific DNA sequences called hormone response elements (HREs).
2. Binding to HREs initiates or enhances the transcription of target genes, leading to the production of specific proteins that carry out the hormone’s effects.

Examples of Steroid Hormones and Their Effects

1. Oestradiol

Oestradiol is a key hormone in the regulation of the menstrual cycle and reproductive processes.

1. Target Cells: Oestradiol acts on cells in the ovary, uterus, and brain.
2. Mechanism: In the hypothalamus, oestradiol binds to its receptor, forming a complex that enters the nucleus and enhances the transcription of the gonadotropin-releasing hormone (GnRH) gene.
3. Outcome: This increases the production of GnRH, which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), critical for ovulation.

2. Progesterone

Progesterone is essential for maintaining the uterine lining during pregnancy.

1. Target Cells: Progesterone acts on cells in the uterus.
2. Mechanism: It binds to its receptor in the cytoplasm, forming a complex that moves into the nucleus and activates genes involved in maintaining the endometrium.
3. Outcome: This ensures the uterine lining remains thick and supportive for a developing embryo.

3. Testosterone

Testosterone is involved in the development of male secondary sexual characteristics and other physiological processes.

1. Target Cells: Testosterone acts on a variety of cells, including those in muscle, bone, and the prostate.
2. Mechanism: It binds to the androgen receptor, forming a complex that enters the nucleus and activates genes responsible for protein synthesis and muscle growth.
3. Outcome: This leads to increased muscle mass, bone density, and the development of male characteristics.

Why Are Intracellular Receptors Important?

1. Direct Gene Regulation: Unlike many other signalling pathways, steroid hormones can directly influence gene expression without relying on secondary messengers.
2. Long-Lasting Effects: The changes induced by steroid hormones are often sustained, affecting processes like growth, development, and reproduction.
3. Specificity: Each hormone-receptor complex targets specific genes, ensuring that only the necessary proteins are produced.

Applications and Implications

Understanding intracellular receptors has practical applications in medicine and biology.

1. Hormone Therapies: Treatments for conditions like hormone imbalances, infertility, and certain cancers rely on manipulating steroid hormone pathways.
2. Drug Development: Synthetic hormones or hormone blockers are designed to target specific receptors, offering treatments for conditions like breast cancer or prostate enlargement.
3. Evolutionary Insights: The conservation of steroid hormone pathways across species highlights their fundamental role in biology.