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Antagonistic Hormones

Round One: Insulin and Glucagon

Round Two: PTH and Calcitonin

What is an antagonistic hormone?

Antagonistic hormones are actually pairs of hormones that work against each other. As we will see, though insulin and glucogon or PTH and Calcitonin work on the same systems, they are constantly fighting against each other in order to maintain homeostasis.

Let's take a closer look at insulin:

How does this hormone utilize signal transduction pathways to cause an effect?

Start video at 2:08

Transduction

Response

Reception

- Receptor activation leads to the phosphorylation of key tyrosine residues on IRS proteins, which activates the PI3-kinase (a lipid kinase). The catalytic subunit of PI3-kinase, then phosphorylates phosphatidylinositol (4,5) bisphosphate [PtdIns(4,5)P2​] which leads to the formation of Ptd(3,4,5)P3. As a result, AKT is recruited to the plasma membrane. Then AKT is phosphorylated by protein kinases. Once active, AKT enters the cytoplasm where it leads to the phosphorylation and inactivation of glycogen synthase kinase 3 (GSK3). A major substrate of GSK3 is glycogen synthase, an enzyme that catalyzes the final step in glycogen synthesis. Phosphorylation of glycogen synthase by GSK3 inhibits glycogen synthesis; therefore the inactivation of GSK3 by AKT promotes glucose storage as glycogen.

Transduced signal triggers a specific action by the target cell:

- Increases cellular uptake of glucose.

- Increases formation of glycogen from glucose in liver/(skeletal) muscle cells.

- Increases rate of intracellular catabolism of glucose.

- Increases fat synthesis from glucose in liver cells and adipose tissue.

Insulin acts as the signaling molecule that comes from outside the cell. It binds to a insulin receptor protein embedded in the cell membrane.

- Basically, after the insulin binds to the receptor protein, it activates the phosphorylation of the tyrosine kinase which in turn continues to transfer phosphate groups from ATP to other protein kinases, activating them. This leads to a phosphorylation cascade that ultimately leads to the storage of glucose in the cell, decreasing the amount in the blood.

In This Corner

Parathyroid Hormone (PTH)

  • Secreted from the four parathyroid glands, which are located in the back of the neck behind the thyroid gland
  • PTH, or Parathryroid Hormone, is a regulatory protein
  • The target cells are in the bones, kidneys, and intestines
  • Parathyroid hormone is regulated by feedback inhibition. Because PTH increases calcium levels in the body, low calcium levels in the blood stimulate hormone production, while high calcium levels prevent production. Small decreases in magnesium in the blood can also stimulate it, while large decreases prevent it
  • Parathyroid hormone and calcitonin work together to contribute to homeostasis because together they keep calcium levels constant.
  • How normal function of PTH works:
  • Bones - Parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream. This increases bone destruction and decreases the formation of new bone.
  • Kidneys - Parathyroid hormone reduces loss of calcium in urine. Parathyroid hormone also stimulates the production of active vitamin D in the kidneys.
  • Intestine - Parathyroid hormone increases calcium absorption in the intestine from food via its effects on vitamin D metabolism.

In This Corner

Insulin

- Insulin is created in the Pancreas.

- Insulin is made of two peptide chains called the A and B chains which are linked together by disulfide bonds. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.

- The liver is the main target organ for Insulin, however most tissue in the body requires insulin, so insulin also targets all cells, except the brain cells. Insulin lowers the blood sugar level by instructing cells to take glucose out of the blood and store it.

- Insulin is controlled and regulated by the islets of Langerhans which are specialized beta cells in the Pancreas that detect an increase in sugar concentration in the blood. Then they release insulin to lower the blood sugar levels.

- The normal function of insulin is to lower sugar levels in blood. It causes glucose to be stored as glycogen. When glucose is stored, it is removed from the blood stream.

LET'S GET READY TO RUMBLE!

If calcium levels in the bones/urine decrease or absorbtion in the instestines increases, PTH is winning.

If there is more calcium in the bones, more calcium in the urine, or less calcium absorbed in the intestinces, calcitonin is winning.

Bibliography

Schlichte, Martin. "Signal Transduction and Hormones." Lecturio Medical Magazine. Lecturio GmbH, 18 Sept. 2015. Web. 28 Oct. 2015. <https://www.lecturio.com/magazine/signal-transduction-and-hormones/>

Bowen, R. "Calcium and Phosphorus Homeostasis." Calcium and Phosphorus Homeostasis. Colorado State University, 11 Oct. 2003. Web. 28 Oct. 2015. <http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcium.html>

Bowen, R. "Calcitonin." Calcitonin. Colorado State University, 11 Oct. 2003. Web. 29 Oct. 2015. <http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/calcitonin.html>

Hasudungan, Armando. "Endocrinology - Calcium and Phosphate Regulation." YouTube. YouTube, 19 May 2015. Web. 29 Oct. 2015. <

Kamerzell, Tim J., Sangeeta B. Joshi, Donald McClean, Lori Peplinskie, Karen Toney, Damon Papac, Meili Li, and C. Russell Middaugh. "Parathyroid Hormone Is a Heparin/polyanion Binding Protein: Binding Energetics and Structure Modification." Protein Science : A Publication of the Protein Society. Cold Spring Harbor Laboratory Press, June 2007. Web. 29 Oct. 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206658/>

"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 21 Jan. 2015. Web. 29 Oct. 2015. <http://www.yourhormones.info/Hormones/Parathyroid_hormone.aspx>

"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 19 Feb. 2015. Web. 29 Oct. 2015. <http://www.yourhormones.info/hormones/glucagon.aspx>

Hooper, Claude, PhD. "Overview of Insulin Signaling Pathways." An Overview of Insulin Signaling Pathways. Abcam Plc, n.d. Web. 01 Nov. 2015. <http://www.abcam.com/pathways/overview-of-insulin-signaling-pathways>

"You & Your Hormones." You & Your Hormones. Society for Endocrinology, 19 Feb. 2015. Web. 01 Nov. 2015. <http://www.yourhormones.info/hormones/insulin.aspx>

And In This Corner

Calcitonin

Insulin and Glucagon fight to maintain homeostasis at 90 mg of glucose for every 100mL of blood.

If there are high levels of glucose in the blood but they are decreased in order to maintain homeostasis, the insulin is working harder and winning.

If there are low levels of glucose in the blood but they are increased in order to maintain homeostasis, the glucagon is working harder and winning.

- Calcitonin is produced by the parafollicular cells, otherwise known as C-cells of the Thyriod gland.

- It is made of a single chain of 32 amino acids containing a single disulfide bond and a ring shaped amino terminus.

- The target organs of Calcitonin are the bones, kidneys, and intestines.

- Calcitonin uses feedback inhibition to regulate Calcium levels in the blood.

- The main function of Calcitonin is to reduce Calcium levels when they are higher than they should be. When high Calcium levels are detected, the secretion of Calcitonin is stimultated.

- Similarly, when Calcium levels are lower than they should be, the production of Calcitonin is stopped.

- In the bones, Calcitonin supresses the reabsorption of Calcium by inhibiting osteoclast activity.

-Osteoclasts are a type of cell that "digests" bone. The inhibition of osteoclasts leads to the release of calcium and phosphorus into the blood. At the same time, Calcitonin stimulates osteoblasts which increase the production of new bone tissue.

- In the kidneys, where Calcium is usually reabsorbed, it is excreted through the urine in higher concentrations.

- The effects of Calcitonin oppose those of the Parathyroid Hormone.

And In This Corner

Glucagon

  • Produced in the pancreas by alpha cells from the islets of Langerhans
  • A protein made of a linear polypeptide of 29 amino acids
  • The target organ is the liver. It prevents the blood sugar from becoming too low by causing the liver to release stored glycogen into glucose for the blood (called glycogenolysis)
  • Controlled and regulated by the islets of Langerhans. These are are specialized cells that detect changes in sugar concentration in the blood and regulate it by releasing either glucagon or insulin to keep a constant concentration of sugar in the blood
  • Normal function of glucagon is to raise sugar level in blood. It causes the breakdown of stored glycogen into glucose. When glucose is released, it raises the sugar level of the blood.
  • It maintains homeostasis of sugar concentration in blood by constantly increasing the amount of sugar in the blood to prevent low sugar concentrations

PTH and calcitonin do opposite tasks, but they work together to maintain homeostasis and calcium levels in the body.

Insulin and Glucagon do opposite tasks, but they work together to maintain homeostasis and glucose levels in the body.

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