Summary
Highlights
The parathyroid glands are located on the posterior aspect of the thyroid gland, typically four in number. Historically, their importance was overlooked during thyroidectomies, leading to complications. They consist of two main cell types: oxyphil cells, whose function is still being researched, and chief cells, which are primarily responsible for secreting parathyroid hormone (PTH).
PTH synthesis begins with gene transcription into mRNA, followed by translation into a protein in the cytoplasm. This protein undergoes modification and packaging in the Golgi apparatus into vesicles. The primary stimulus for PTH release is low blood calcium levels, also known as hypocalcemia. A calcium-sensitive receptor on chief cells inhibits PTH release when calcium levels are high, and this inhibition is lessened when calcium levels are low, leading to PTH secretion. This process is an example of humoral stimuli.
The thyroid gland also contains parafollicular or C cells, which produce calcitonin. Unlike PTH, calcitonin release is stimulated by high blood calcium levels (hypercalcemia). Calcitonin synthesis similarly involves gene transcription, translation, and packaging into vesicles. High calcium levels signal the parafollicular cells to release calcitonin into the bloodstream, also through a humoral stimulus.
PTH's main goal is to increase blood calcium levels. It acts on bone tissue by interacting with osteoblasts, which then release Rank Ligand. Rank Ligand binds to Rank receptors on osteoclasts, activating them. Activated osteoclasts perform bone resorption, breaking down bone tissue and releasing calcium and phosphate into the blood, thereby increasing circulating levels of these ions.
In the kidneys, PTH, a protein hormone, binds to extracellular receptors on cells of the distal convoluted tubule. This binding activates a G stimulatory pathway, leading to the production of specific calcium channel proteins. These channels are embedded in the cell membrane, allowing calcium from the filtrate to be reabsorbed into the kidney cells and subsequently into the blood. This process, involving a sodium-calcium exchanger, increases blood calcium levels while also promoting the excretion of phosphates.
PTH indirectly contributes to increasing blood calcium by activating vitamin D. In the skin, UV light converts 7-dehydrocholesterol into cholecalciferol. Cholecalciferol is then hydroxylated in the liver by 25-hydroxylase to become 25-hydroxycholecalciferol. PTH stimulates the kidney to express 1-alpha hydroxylase, which converts 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol, also known as calcitriol or active vitamin D. This active vitamin D is crucial for calcium absorption.
Active vitamin D (calcitriol) acts on intestinal epithelial cells (enterocytes). Being a steroid hormone, it binds to intracellular receptors, activating gene sequences that produce calcium channel proteins. These proteins are inserted into the cell membrane, enhancing the absorption of dietary calcium from the gut into the bloodstream, thus increasing blood calcium levels.
Calcitonin is released in response to high blood calcium levels and works to decrease them. Its primary target is bone. Calcitonin binds directly to receptors on osteoclasts, inhibiting their activity. This suppression of osteoclast activity shifts the balance towards osteoblast activity, which involves taking calcium from the blood and depositing it into bone tissue, leading to decreased blood calcium levels and increased bone density.