Mechanism of Action of Hormones with Intracellular Receptors
These hormones are lipid-soluble, so they can cross the cell membrane easily.
Their receptors are located inside the cell, either:
- In the cytoplasm, or
- Directly in the nucleus
Once they bind their receptor, the hormone-receptor complex acts as a transcription factor, meaning it binds DNA and influences gene expression.
This leads to long-lasting effects such as protein synthesis, growth, differentiation, and metabolic adjustments.
The response is slower to begin, but longer-lasting than cell membrane receptor mechanisms.
Steroid Hormones (e.g., cortisol, aldosterone, estrogen, testosterone)
Because they are derived from cholesterol, they are hydrophobic and diffuse through the membrane.
- The hormone enters the cell and binds to a specific intracellular receptor.
- If the receptor is in the cytoplasm, the hormone–receptor complex then moves into the nucleus.
- The complex binds to specific DNA regions known as Hormone Response Elements (HREs).
- This activates or represses the transcription of target genes.
- Over time, this leads to increased or decreased protein synthesis.
This is why steroids regulate:
- Growth and development
- Immune responses
- Salt-water balance
- Reproduction and sexual differentiation
The effects are gradual but powerful.
Thyroid Hormones (T₃ and T₄)
Thyroid hormones also cross the membrane, but their receptors are already inside the nucleus, bound to DNA even before the hormone arrives.
However, without hormone, these receptors keep genes turned off.
When T₃ (more active form) binds the receptor:
- The receptor changes shape and starts activating transcription of genes involved in:
- Basal metabolic rate (↑)
- Mitochondrial activity (↑ ATP production)
- Heat production
- Growth and brain development (especially in infants and children)
This is why lack of thyroid hormone early in life causes cretinism and developmental delay.
T₄ is converted to T₃ inside tissues to fine-tune the response.
Calcitriol / Vitamin D (the “sunshine hormone” of calcium metabolism)
Vitamin D is modified in the liver and kidney to form calcitriol, the active hormone.
Calcitriol behaves like a steroid hormone:
- It enters the cell
- Binds to a nuclear receptor
- The hormone–receptor complex stimulates gene expression
Its major effects include:
- Increasing intestinal absorption of calcium and phosphate
- Regulating bone mineralization
- Supporting immune function
- Working together with PTH to maintain calcium homeostasis
If calcitriol levels fall:
- Bones weaken (rickets in children, osteomalacia in adults)
Vitamin D as a Special Case
Although structurally different from steroids, its mechanism is almost identical to intracellular steroid hormone action:
- Lipid soluble
- Nuclear receptor binding
- Regulation of gene transcription