From the Guidelines
Parathyroid Hormone (PTH) and Parathyroid Hormone-related Protein (PTHrP) are distinct molecules with different origins, structures, and physiological roles, despite sharing some overlapping functions in calcium metabolism, as noted in studies such as 1 and 1. The key differences between PTH and PTHrP lie in their production sites, structures, and primary functions. PTH is produced by the parathyroid glands and plays a crucial role in regulating calcium and phosphate homeostasis in the body by acting on bone and kidneys. It consists of 84 amino acids and is secreted as an endocrine hormone. In contrast, PTHrP is produced by various tissues, including certain cancers, and shares structural similarity with PTH only in its N-terminal region (the first 13 amino acids). This similarity allows PTHrP to bind to the same PTH receptor (PTH1R), explaining their overlapping effects on calcium metabolism, as discussed in 1.
Some of the main differences between PTH and PTHrP include:
- Origin: PTH is produced by the parathyroid glands, while PTHrP is produced by various tissues throughout the body.
- Structure: PTH consists of 84 amino acids, while PTHrP has a similar structure to PTH in its N-terminal region but differs significantly in the rest of the protein.
- Function: PTH primarily regulates calcium and phosphate homeostasis, while PTHrP has more diverse roles, including paracrine and autocrine regulation in normal physiology, and is involved in fetal development, lactation, cartilage differentiation, mammary gland development, tooth eruption, and smooth muscle relaxation, as mentioned in 1 and 1.
- Mode of action: PTH circulates systemically as an endocrine hormone, while PTHrP typically acts locally, except in pathological conditions like humoral hypercalcemia of malignancy, where it can be secreted into circulation in excessive amounts.
Understanding these differences is crucial for the diagnosis and management of conditions related to calcium metabolism, such as hypercalcemia of malignancy, where PTHrP plays a significant role, as discussed in 1. Accurate measurement of PTH and distinction between PTH and PTHrP are essential for proper clinical interpretation and treatment, as highlighted in 1 and 1. Therefore, it is essential to consider the specific roles and characteristics of both PTH and PTHrP in clinical practice to ensure appropriate diagnosis and management of related conditions, prioritizing morbidity, mortality, and quality of life as outcomes, based on the most recent and highest quality evidence available, such as the studies referenced here 1.
From the Research
Overview of PTH and PTHrP
- Parathyroid Hormone (PTH) and Parathyroid Hormone-related Protein (PTHrP) are two peptides that play crucial roles in regulating extracellular phosphate and calcium homeostasis, as well as bone remodeling 2.
- PTH is a classic endocrine peptide hormone produced by the parathyroid glands, whereas PTHrP is ubiquitously expressed and acts in an autocrine/paracrine manner 2, 3.
Differences in Regulation and Secretion
- PTH is regulated by negative feedback from multiple factors and is released from the parathyroid glands in response to low calcium levels 2.
- PTHrP, on the other hand, is not subject to the same regulatory mechanisms as PTH and is produced by a wide range of tissues, including normal and malignant cells 3, 4.
Receptor Binding and Biological Effects
- Both PTH and PTHrP bind to the same receptor, the PTH/PTHrP receptor, which is a class B G-protein-coupled receptor 5.
- The different biological effects of PTH and PTHrP result from their modes of regulation and secretion, with PTH having a more systemic effect and PTHrP acting locally in an autocrine/paracrine manner 5.
Clinical Implications
- Primary hyperparathyroidism is characterized by excessive secretion of PTH, leading to hypercalcemia and other clinical manifestations such as osteoporosis and nephrolithiasis 3, 6.
- PTHrP is often associated with hypercalcemia of malignancy, but it can also be produced by normal tissues and play a role in various physiological processes 3, 4.
- The diagnosis of primary hyperparathyroidism is based on hypercalcemia and elevated levels of PTH, while the presence of PTHrP can be detected using specific assays 4.