Hormones of the Liver

• Insulin-like Growth Factor-1 (IGF-1)
• Angiotensinogen
• Thrombopoietin

Insulin-like Growth Factor-1

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). 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.

Angiotensinogen

Thrombopoietin (TPO)

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.

• 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.

A segment of thrombopoietin, manufactured by recombinant DNA technology, is now available for human therapy. It already shows promise in quickly restoring normal platelet counts in patients who have undergone chemotherapy.