| Abstract: | We propose that intracellular prostaglandins (PGs) are essential for the final expression of the effects of second messengers in most cells. We suggest that the amounts of PGs required are very small (in the picomolar range) and are much lower than those used in most current PG studies. We suggest that while therapeutic levels of inhibitors of PG synthetase may be adequate to block the overflow of PGs from cells, they are in most cases unlikely to reduce intracellular PGs sufficiently to test the role of such PGs. We propose that there is a basal level of PG synthesis unaffected by hormones but that above this level PG synthesis is regulated by the interplay between physiological levels of cortisol, prolactin, growth hormone and thyroid hormones. For the most part prolactin seems to stimulate PG synthesis and cortisol to inhibit it: cortisol has, however, no inhibitory effect on basal PG synthesis. In reducing prolactin-stimulated PG synthesis cortisol is 1000-2000 times more potent than indomethacin on a molar basis. We suggest that the regulation of intracellular PG levels is the mechanism of the so-called "permissive" actions of these hormones. These concepts could prove important in the understanding of many aspects of physiology and pathophysiology including diurnal and seasonal changes in hormone responsiveness. They are also relevant to the use of established drugs and the design of new ones. |
