PTHdependent

PTHdependent refers to biological processes, tissues, or responses that require parathyroid hormone (PTH) signaling to occur or be modulated. In physiology, many calcium and phosphate homeostasis mechanisms are PTH-dependent, particularly in bone and kidney. In bone, PTH acts on osteoblasts and osteocytes via PTH1R, increasing the expression of RANKL and decreasing osteoprotegerin, which promotes osteoclast formation and bone resorption. This mobilizes calcium and phosphate into the bloodstream. Conversely, intermittent PTH exposure can have anabolic effects on bone by stimulating osteoblast activity when administered as therapy.

In the kidney, PTH increases calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule, contributing to higher serum calcium and lower serum phosphate. PTH also stimulates renal 1α-hydroxylase, converting 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, which enhances intestinal calcium and phosphate absorption. These kidney and bone actions describe classic PTH-dependent pathways maintaining calcium homeostasis.

PTH-dependent signaling hinges on the PTH1 receptor, a G protein–coupled receptor that activates cAMP/PKA and, in some contexts, PLC pathways. Gene expression changes in osteoblasts and renal tubules under PTH influence, including increased RANKL and CYP27B1, illustrate molecular mechanisms behind the term.

Clinical relevance includes conditions of altered PTH signaling, such as hyperparathyroidism with PTH-dependent hypercalcemia or hypoparathyroidism with low PTH activity. Therapeutically, PTH or PTH analogs (e.g., teriparatide) exploit PTH-dependent effects for osteoporosis treatment, highlighting the dual anabolic and catabolic potential of PTH signaling depending on exposure pattern.