Endocrine System

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Questions Received:

  1. What causes the 'hot flushes' of menopause?

  2. What are prostaglandins? How are they involved in inflammation?

  3. How are prostaglandins being used today?

Responses:

What causes the 'hot flushes' of menopause?

The following reference provides a useful summary:

Abstract

Hot flashes are the most frequent somatic complaint of women going through the menopause. Although the exact pathophysiology of the hot flash remains unknown, it appears to be related to an alteration in the set point of the hypothalamic thermoregulatory center. With the withdrawal of estrogen, some event parallel to the release of GnRH (and subsequent release of LH) causes a decrease in the set point of the thermoregulatory center. The hot flash, with its characteristic sweating and vasodilation, represents the attempt to decrease the body core temperature and restore equilibrium. Estrogen therapy reliably treats hot flashes in the majority of women in addition to its proven beneficial effect on heart disease and osteoporosis. It is rare that health care providers can so reliably and safely positively impact on a patient's symptoms and overall health.

What are prostaglandins? How are they involved in inflammation?

15th September 1998

Prostaglandin MoleculeProstaglandins belong to a family of chemical messengers that have been studied intensively over the last 15-20 years. Prostaglandins were first identified in semen, and received their name because at that time they were thought to originate from the prostate gland. However, we now know that the prostaglandins in semen are synthesised mainly by the seminal vesicles, and the prostate makes only a small contribution. Furthermore, it has been discovered that prostaglandins are produced in almost all tissues of the body, and are ubiquitous messenger molecules with a variety of actions. They are fatty acids synthesised from arachidonic acid (a long chain polyunsaturated fatty acid), and have been classified into groups from prostaglandin A to prostaglandin I according to structural variations in the five-carbon ring at one end of the molecule. There is further subdivision based on the number of double-bonds in the two side chains.

Prostaglandins are paracrine secretions (local hormones) - they are released from cells and bring about changes in neighbouring cells that carry specific prostaglandin receptors in their membranes. They are rapidly degraded locally, and generally do not reach the blood stream.

The influence which prostaglandins have depends upon the type of tissue they are acting upon. Such action may be direct, or as a result of modifying the actions of other signalling molecules. Prostaglandins are released by damaged cells and nearby macrophages, and one of their effects is to stimulate pain receptors (nociceptors). At the same time they intensify the effects of other chemical mediators such as histamine and bradykinin. Acting in concert these substances can bring about vasodilatation and an increase in the permeability of capillaries supplying the damaged area, encouraging the migration of phagocytes from the blood through capillary walls into the damaged tissue. As a result of these changes, the blood supply to the area increases, the tissues swell, and pain occurs, signs of inflammation.

Inhibition of Prostaglanding SynthesisFever often accompanies inflammation, and can be triggered either by pyrogens from infectious organisms or by prostaglandin. Twenty years ago, prostaglandin E2 was proposed as an important mediator of the fever response in the brain, and this has now been confirmed (Ushikubi 1998). Remarkably, this link between prostaglandin and fever has been observed in a wide range of species, from invertebrates to mammals.

The benefits obtained by administering aspirin or other non-steroidal anti-inflammatory drugs such as indomethacin and ibuprofen to relieve pain and fever are due to inhibition of the synthesis of prostaglandin (Allen, 1995).

Aspirin is a salicylate derived from the inner bark of willow trees, and has been used medicinally by several cultures for many centuries.

 

References

For overviews of prostaglandins and their actions, see:

(See also - cytokines.)

For some attractive micrographs of prostaglandins, visit:

http://micro.magnet.fsu.edu/micro/gallery/prostaglandin/prost3.html

How are prostaglandins being used today?

27th April 1999

Prostaglandins have significant biological effects within the body, and as we gain a better understanding of their actions the number of therapeutic interventions involving prostaglandins increases commensurately. Here are several examples (for more information see The British National Formulary 1996):

Reference

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