Thu7October0140PM 10

Parathormone (PTH) is a regulator of calcium homeostasis.

Which one of the following actions of PTH is most likely to lead to the release of calcium from bone?

(Please select 1 option)

Interaction with PTH2 receptors

Indirect stimulation of osteoclasts Correct

Direct stimulation of osteoclasts

Direct simulation of osteoblasts

Indirect stimulation of osteoblasts

Explanation

Parathyroid hormone (PTH) and parathyroid hormone type 1 receptor (PTH1-Rc) are major players in regulating blood calcium homeostasis.

In bone, PTH can induce a rapid release of calcium from the matrix, but it also mediates longer term changes in calcium metabolism by acting directly on bone forming osteoblasts (by binding to PTH1-Rc) and indirectly on osteoclasts, the bone-resorbing cells.

PTH action on osteoblasts leads to changes in the synthesis and/or activity of several proteins, including osteoclast-differentiating factor, also known as TRANCE or RANKL.

Osteoclast precursors have RANK receptors on their cell surfaces. When RANKL binds to the RANK receptors this activates the osteoclasts. Osteoclasts do not have receptors to PTH, while osteoblasts do. Osteoclasts require indirect activation by the RANK receptor binding to RANKL secreted by osteoblasts, which then leads to bone resorption. Osteoclasts do have PTH1 receptors but are sparse.

PTH activates G-protein coupled receptors via adenylate cyclase of all target cells.

The PTH2 receptor is present at greatest levels in the nervous system and pancreas and is not a regulator of calcium metabolism. It is found in the cerebral cortex and basal ganglia and at relatively high abundance in the septum, midline thalamic nuclei, several hypothalamic nuclei, and the dorsal horn of the spinal cord. Peripherally, expression in pancreatic islet somatostatin cells is most dramatic.

Functional hypotheses based on the receptor's distribution are being tested. It may be involved in the control of hypothalamic releasing-factor secretion and pain modulation.

Answer Statistics

1

2%

2

28%

3

64%

4

5%

5

3%

Times answered: 231