Thyroid and Adrenal Glands

2.4. Mechanism of Action of Adrenocortical Hormones

• The adrenocortical hormones—mineralocorticoids, glucocorticoids, and androgens—are all steroid hormones synthesized from cholesterol in the adrenal cortex.
• Because of their lipid-soluble nature, they easily diffuse across cell membranes and act primarily by altering gene expression to regulate protein synthesis within target cells.

• Diffusion into Target Cell:

  • Being lipid-soluble, adrenocortical hormones pass freely through the cell membrane.

• Binding to Intracellular Receptors:

  • Inside the target cell, the hormone binds to a specific cytoplasmic or nuclear receptor (a member of the steroid receptor family).

  • Examples:

    • Mineralocorticoid receptor (MR) – for aldosterone

    • Glucocorticoid receptor (GR) – for cortisol

• Hormone–Receptor Complex Formation:

  • The hormone–receptor complex undergoes conformational activation, exposing a DNA-binding domain.

• Translocation to the Nucleus:

  • The activated complex enters the cell nucleus and binds to specific hormone response elements (HREs) on DNA.

• Regulation of Gene Transcription:

  • The complex either stimulates or suppresses transcription of specific genes.

  • This leads to the synthesis (or inhibition) of particular mRNAs and, subsequently, proteins that mediate the hormone’s effects.

• Cellular Response:

  • The newly synthesized proteins bring about long-term changes in cell function—such as enzyme production, ion transport, or metabolic regulation.

  • Because this process depends on transcription and translation, the effects of adrenocortical hormones are slow in onset but long-lasting.