The liver synthesizes and secretes at least four important hormones:
- Insulin-like Growth Factor-1 (IGF-1)
Insulin-like Growth Factor-1
This protein of 70 amino acids was once called somatomedin because it is not growth hormone but is the immediate stimulus for growth of the body. Growth hormone released from the anterior lobe of the pituitary binds to receptors on the surface of liver cells which stimulates the synthesis and release of IGF-1 from them. Many cells have receptors for IGF-1, especially cells in the bone marrow and in the cartilaginous growing regions of the long bones.
Binding of IGF-1 to cells with receptors for it stimulates them to move from G1 of the cell cycle to S phase and on to mitosis.
Mice with one of their Igf-1 receptor genes "knocked out" live 25% longer than normal mice. This may result from an increase in their resistance to the damaging effects of reactive oxygen species (ROS) or to an increased efficiency at clearing away clumped proteins in their cells (or both). These heterozygous mice appear to be normal in every other respect.
The levels of IGF-1 in the blood are highest during the years of puberty which is, of course, a time of rapid growth. Occasionally children are found that have stunted growth because they have inherited mutant genes for the growth hormone (GH) receptor. Recombinant human IGF-1 has been successfully used to treat them.
This protein is released into the blood where it serves as the precursor for angiotensin. How angiotensin is manufactured, and the role it plays in maintaining blood pressure, is described in the discussion of renin.
Thrombopoietin is a protein of 332 amino acids. It stimulates precursor cells in the bone marrow to differentiate into megakaryocytes. Megakaryocytes generate platelets, essential to blood clotting.
The production of megakaryocytes — and thus platelets — is under homeostatic control. It works like this:
- Circulating platelets are covered with receptors for TPO.
- So are megakaryocytes and their precursors, but there are fewer of them.
- When platelet counts are high, most of the circulating TPO is bound to the platelets and less is left to stimulate megakaryocytes.
- When platelet counts drop, more TPO becomes available to stimulate megakaryocytes to replenish the platelet supply.
- Humans manufacture about 1011 platelets each day under normal conditions.
Hepcidin is a peptide of 25 amino acids. It blocks the release of iron from intracellular stores in the body. This function not only helps to maintain homeostatic levels of iron in the body fluids but also serves as a defense against invasion by pathogenic bacteria. Many pathogens require substantial amounts of iron for their virulence and the release of hepcidin in response to infection starves them of this needed iron. Thus hepcidin qualifies as an antimicrobial peptide and part of the innate immune system.
Betatrophin is a protein of 193 amino acids that stimulates the proliferation of the insulin-secreting beta cells of the pancreas. Perhaps injections of betatrophin, made by recombinant DNA technology, may turn out to be a useful treatment for diabetes mellitus.