Parathyroid Hormone (PTH)
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Calcium Homeostasis | Parathyroid Hormone and Vitamin D
Will lowering my PTH with calcium reverse my atherosclerosis?
If PTH is mid-normal, do I need a calcium supplement?
What If My Vitamin D Is Normal But My PTH Is High?
Acts on:
Bone:
Parathyroid hormone can act on bone tissue. There are two different types of bone cells, osteoclasts and osteoblasts.
Osteoclasts for bone resorption, breaks the bone down to leach out calcium & phosphate to put it into the plasma. Osteoblasts are responsible for bone deposition, take calcium certain types of phosphates and amino acids to deposit it into the bone tissue.
The stimulus for parathyroid hormone was low blood calcium, so its goal is to increase blood calcium by stimulating osteoclast break down of bone. How it works is a little weird because osteoclasts and osteoblasts like to talk to each other. So Parathyroid hormone talks to osteoblasts first, then the osteoblast will talk to the osteoclast. There’s a receptor for PTH on the osteoblast and when PTH binds on to it, it stimulates the osteoblast to secrete a specific chemical to the osteoclast, RANK-ligand. Osteoclasts have RANK receptors. When RANK ligand binds on to the RANK receptor, it triggers the osteoclast to become very active and it starts secreting chemicals like Cathepsin K (a protein digesting enzyme), acid phosphatases, and other chemicals, to break down some of the chemicals in the bone like collagen type 1, calcium phosphates…a lot of calcium and phosphate are accumulating from this breakdown which are moved into the blood.
Kidney
PTH works in the cells of the Distal Convoluted Tubule of the nephron.
Receptors on the cells of the Distal Convoluted Tubule use the G stimulatory (Gs) pathway for PTH. When PTH binds on to it, an intracellular pathway is stimulated. Gs activates Adenolate cyclase, which uses ATP to make cAMP, cCAMP activates protein kinase a, the overall result is phosphorylation of transcription factors for specific types of calcium channel protein molecules.
Normally the cells in the Distal Convoluted Tubule are very resistant to ions (sodium, chlorine, iron, water) so usually by the time the filtrate gets to this point, hormones need to be present in order to open up specific channels to get those ions in or they’ll be lost in the urine. Calcium could be chilling out in the actual lumen of this filtrate, getting ready to leave the body. PTH made calcium channels on the membranes of these cells just in time to capture calcium before it left the body in urine.
As calcium enters the cell from the filtrate, it’s moving against the concentration gradient (moving from areas of low inside the cell, to high, in the blood) so it can’t get out of the cell back into the blood. Assistance is required. Every single cell in our body has special types of channels called sodium-potassium ATPase pumps (active transport). They are pumping 3 sodium ions out the cell into the extracellular space and 2 potassium ions from the extracellular space into the cell. When the sodium gets concentrated in the extracellular space, through passive diffusion, the sodium will move out into the blood, and from there, through a channel back into the cell that’s holding so much calcium….when that sodium enters the channel it helps calcium get out and into the blood. An example of a sodium-calcium exchanger called “secondary active transport”. Then end results is an increase in the calcium blood levels.
Since phosphates are an important part of the buffering system, when calcium is being brought back into circulation through these cells via PTH, at the same time this hormone is secreting out phosphorus to maintain buffering.
Vitamin D & Calcium levels
In the skin there’s a chemical called 7-dehydrocholesterol. When UV sunlight hits the skin, it acts as a stimulus to cause 7-dehydrocholesterol to get pulled into the blood where it’s turned into another type of molecule, cholecalciferol (CCF). Once CCF is in the blood it goes to the liver. In the liver there’s an enzyme that loves to put hydroxyl groups onto molecules (-OH groups), its called 25-hyroxylase. It puts an OH group on the 25th carbon of cholecalciferol, this comes out into the blood as 25-hydroxycholecalciferol.
PTH acts on tubular cells in the kidney to cause them to express an enzyme, 1-alpha-hydroxylase.
The 25-hydroxycholecalciferol travels to the kidney where it interacts with 1-alpha-hydroxylase which puts an -OH group on the first carbon. Now we call it 1,25-dihydroxycholecalciferol, another name for it is calcitrol. This is the active form of vitamin D.
What is vitamin D going to do?
Let’s look at the first part of the small intestine, the duodenum, at an enterocyte (an intestinal epithelial cell). Vitamin D travels to these cells (vitamin D acts like a steroid hormone so it can move through the lipid bilayer of the cell membrane with need for transporters or receptors on the membrane)…it’s receptors are on the inside of the cells. When it binds onto the receptor it activates a specific gene sequence resulting in calcium channel proteins, embedded in the cell membrane to help us extract calcium from our food.