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August 8, 2014

Prostaglandins

by Helene van den Berg

THREE FAMILIES OF PROSTAGLANDINS:

There are three families of natural fats in the foods we eat. Each family is converted into special hormones called prostaglandins (Pgs). Our body needs all three types of fats in balanced amounts, because we need all three types of Pgs (Pg1, Pg2, Pg3 in balanced amounts), to make our cells work.

A prostaglandin is any member of a group of compounds derived from fatty acids (in cell membranes or circulate in the body as free fatty acids, phospholipids and cholesterol esters). They contain 20 carbon atoms, including a 5-carbon ring. The prostaglandins together with thromboxanes, form the prostanoid class of fatty acid derivatives; the prostanoid class is a subclass of eicosanoids.

They differ from hormones in that they are not produced at a specific site but in many places throughout the human body; also, their target cells are present in the immediate vicinity of the site of their secretion. The PG hormones are potent, but have a short half-life before being inactivated or excreted; therefore they are not endocrine hormones, but autocrine (acting on the same cell from which it is synthesized) and paracrine (locally active). Pgs are constantly being produced and their effects on the tissues are of major importance. Prostaglandins have a variety of biochemical and physiological effects, including hormonal effects. Since the types of foods we eat influences the prostaglandins made in the body, foods therefore influence the hormonal status in the body. PG’s act as intermediates between hormones, neurotransmitters and metabolic stimulants. PG hormones mediate the control of local tissue effects such as regulating inflammation, cause platelet aggregation/disaggregation, sensitize spinal neurons to pain, induce labor, regulate calcium movement, regulate hormones (catecholamines), increase glomerular filtration rate, tumor growth, produce fever, inhibit acid secretion etc.

NATURAL SUPPLEMENTS AND HERBS that influence prostaglandins:

  • Curcumin (turmeric)- a polyphenolic antioxidant and has anticancer activity; inhibits PGE2 production
  • Mangosteen – inhibit histamine release and PGE2 synthesis;
  • Pomegranate juice- retard oxidation and prostaglandin synthesis; inhibit breast cancer cell proliferation and invasion.
  • Prostaglandin gel – medication used to soften and thin the cervix (past your due date or have a large baby).

Prostaglandin antagonists are:

  • NSAIDs – long term use of aspirin and ibuprofen can decrease the incidence of certain malignancies like colorectal cancer, oesophageal cancer, breast cancer, lung cancer and bladder cancers. The targets of NSAIDS are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins and thromboxane.
  • COX -2 selective inhibitors – PG E2 can promote tumour growth and is the principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis. Nonsteroidal anti-inflammatory medications (NSAIDS) and selective cyclooxygenase-2 (COX-2) inhibitors, reduce PG E2 production to diminish the inflammation in these diseases, BUT have toxicities that may include gastrointestinal bleeding and prothrombotic tendencies. An omega-3 rich diet, is associated with a reduction in prostate tumor PG E2 levels.
  • Corticosteroids
  • Cyclopentenone prostaglandins- inhibit inflammation.
  • Future medications that inhibit the action of PG D2 should delay male pattern baldness.

Clinical uses:

  • To induce childbirth or abortion
  • Treat peptic ulcers
  • As a vasodilatorischemia of a limb/ Raynaud’s phenomenon.
  • Pulmonary hypertension
  • Treating glaucoma
  • Erectile dysfunction: (Prostaglandins E1 – may be beneficial for some patients with erectile dysfunction and peripheral arterial occlusive diseases).

SYNTHESIS:

Prostaglandins are produced from the enzyme-controlled oxidation of fatty acids AA, DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases. Prostaglandins are produced following the sequential oxidation of COX-1, is responsible for the baseline levels of prostaglandins; COX-2 produces prostaglandins though stimulation. However, while COX-1 and COX-2 are both located in the blood vessels, stomach, kidneys, prostaglandin levels are increased by COX-2 in scenarios of inflammation. There are several dozen prostaglandins and each have very different and very specific functions.

Prostaglandins for practical purposes, can be classified in 3 groups (depending on which fatty acid they are made from):

  • Series 1 prostaglandins (PG1) are made from gamma linoleic acid (GLA), with linoleic acid as the starting point. This series of prostaglandins relax blood vessels, improve circulation, lower blood pressure, decrease inflammation, improve nerve function, regulate calcium metabolism, improve T-cell function and prevent the release of arachidonic acid (AA) from cells (“bad” prostaglandins).
  • Series 3 prostaglandins (PG3) are made from EPA (fatty acid found in fish oil), with linolenic acid as the starting point. Their most important job is to prevent AA (“bad” prostaglandins) from being released by cells.
  • Series 2 prostaglandins (PG2) are made from arachidonic acid (AA). They promote platelet aggregation (clot formation), inflammation sodium retention, influence heart disease, blood clots, increase cortisol production etc. Reducing prostaglandins 2 is a good option to stay healthier.
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