Parathyroid hormone (PTH) is a regulator of calcium levels in the bloodstream. When calcium concentration dips, the parathyroid glands release PTH to restore this balance. The hormone circulates until it finds target cells equipped with receptors that recognize and bind to it. This interaction is like a key fitting into a lock, initiating a cellular response. This binding is the first step in a cascade of events that elevates blood calcium.
Primary Locations of PTH Receptors
The primary receptor for parathyroid hormone, the parathyroid hormone 1 receptor (PTH1R), is found in high concentrations in two main areas: bone and the kidneys. These are the principal sites where PTH exerts its direct effects. In bone tissue, PTH1R is not located on the cells that break down bone, but on bone-building cells called osteoblasts. This distinction is important for understanding how the hormone extracts calcium from the skeleton.
In the kidneys, these receptors are densely populated on the cells that form the renal tubules. These tubules are structures responsible for filtering blood and forming urine, and the presence of PTH1R allows the kidneys to respond directly to the hormone’s signals. By having receptors in these two tissues, PTH orchestrates a coordinated response to low blood calcium.
Role of Receptors in Bone Tissue
When PTH binds to its receptors on osteoblasts, it does not cause these cells to build more bone. Instead, the binding initiates a signaling cascade within the osteoblast. This signal causes the osteoblasts to produce a molecule called Receptor Activator of Nuclear Factor-κB Ligand (RANKL). This molecule acts as a messenger to a different type of bone cell.
The RANKL expressed by osteoblasts then binds to a corresponding receptor, RANK, on immature osteoclast precursor cells. This binding signals these precursors to mature and become active osteoclasts. Activated osteoclasts are responsible for bone resorption, the process of breaking down the mineralized matrix of bone. This breakdown releases stored calcium and phosphate from the bone into the bloodstream.
Role of Receptors in the Kidneys
The binding of PTH to its receptors in the renal tubules triggers several effects. The first action is to increase the reabsorption of calcium. As blood is filtered, calcium is prevented from being lost in the urine and is returned to circulation. This process occurs in the distal tubules of the kidney.
Simultaneously, PTH binding inhibits the reabsorption of phosphate, leading to increased excretion of phosphate in the urine. This is a complementary action because high levels of phosphate can bind with calcium in the blood, reducing the amount of free, active calcium. By expelling excess phosphate, PTH ensures that the newly mobilized calcium remains available.
A third function of PTH in the kidneys is the stimulation of the enzyme 1-alpha-hydroxylase. This enzyme is responsible for the final conversion of inactive Vitamin D into its active form, calcitriol. This activation step is a link between the direct actions of PTH and its influence on the digestive system.
The Indirect Influence on Intestinal Absorption
PTH does not have a direct effect on the intestines because its cells do not have PTH receptors. The hormone’s influence on calcium absorption from food is indirect, mediated by the active Vitamin D produced in the kidneys. The calcitriol, synthesized due to PTH stimulation, travels through the bloodstream to the small intestine.
Once at the small intestine, calcitriol binds to its own specific receptors on intestinal epithelial cells. This binding increases the synthesis of calcium-binding proteins and calcium channels. These proteins facilitate the transport of calcium from digested food across the intestinal wall and into the bloodstream. This mechanism increases the uptake of calcium from dietary sources.