Hormones of the Kidney, Skin, and Heart

1. Kidney

• Renin
• Erythropoietin (EPO)
• Calcitriol (1,25[OH]₂ Vitamin D₃)

Renin

• Renin acts on angiotensinogen, a plasma protein, splitting off a fragment containing 10 amino acids called
• angiotensin I.
• angiotensin I is cleaved by a peptidase in the lungs, producing
• angiotensin II, which contains 8 amino acids.
• angiotensin II
  • Constricts the walls of arterioles closing down capillary beds.
  • Stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim more sodium and thus water [Discussion].
  • Increases the strength of the heartbeat
  • Stimulates the pituitary to release the antidiuretic hormone (ADH, also known as arginine vasopressin).
  All of these actions lead to an increase in blood pressure.

Erythropoietin (EPO)

Erythropoietin is a protein. It acts on the bone marrow to increase the production of red blood cells. Stimuli such as bleeding or moving to high altitudes (where oxygen is scarcer) trigger the release of EPO.

People with failing kidneys can be kept alive by dialysis. But dialysis only cleanses the blood of wastes. Without a source of EPO, these patients suffer from anemia.

Now, thanks to recombinant DNA technology, recombinant human EPO is available to treat these patients. Some of the drugs used to treat AIDS, zidovudine (AZT) for example, cause anemia as a side effect. Recombinant EPO helps AIDS patients cope with this one of the many problems that the disease creates.

Calcitriol

• calciferol (vitamin D₃) which is synthesized in skin exposed to the ultraviolet rays of the sun
• precursors ("vitamin D") ingested in the diet.

• calciferol is converted in the liver into 25[OH] vitamin D₃
• this is carried to the kidneys where it is converted into calcitriol. This final step is promoted by the parathyroid hormone (PTH).

Calcitriol Action

Calcitriol acts on the cells of the intestine to promote the absorption of calcium from the diet.

Calcitriol diffuses into cells and, if they contain receptors for it (intestine cells do), it binds to the receptor molecules. The receptor-ligand complex now can bind to its response element:

This sequence of nucleotides (n can be any nucleotide) is found in the promoters of genes that are turned on by calcitriol. Once the hormone-receptor complex is bound to its response element, other transcription factors are recruited to the promoter and transcription of the gene(s) begins.

Deficiency disorders

• In childhood, this produces the deformed bones characteristic of rickets.
• In adults, it produces weakened bones causing osteomalacia.

The most common causes are inadequate amounts of the vitamin in the diet or insufficient exposure to the sun.

However, some rare inherited cases turn out to be caused by inheriting two mutant genes for the kidney enzyme that converts 25[OH] vitamin D₃ into calcitriol.

2. Skin

• When ultraviolet radiation strikes the skin, it triggers the conversion of dehydrocholesterol (a cholesterol derivative) into calciferol (vitamin D₃).
• Calciferol travels in the blood to the liver where it is converted into 25[OH] vitamin D₃.
• This compound travels to the kidneys where it is converted into calcitriol (1,25 [OH]₂ vitamin D₃). This final step is promoted by the parathyroid hormone (PTH)

Although called a vitamin, calciferol and its products fully qualify as hormones because they are

• made in certain cells,
• carried in the blood,
• affect gene transcription in target cells.

3. Heart

Atrial natriuretic peptide (ANP)

• one, of 28 amino acids, from the stretched atria called atrial natriuretic peptide (ANP) and
• a second (of 32 amino acids) from the ventricles.

• relaxing arterioles
• inhibiting the secretion of renin and aldosterone
• inhibiting the reabsorption of sodium ions by the kidneys.

These effects give ANP its name (natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood in the circulatory system.