Further studies on prostaglandin E2 (PGE2)-induced gonadotropin release: comparison with the effect of 15-methyl PGE2, PGAs, PGBs and prostaglandin endoperoxide analogs.

It is known that PGE2 is a potent stimulus of LH release. To determine if the effect of PGE2 could be enhanced and/or prolonged by retarding its metabolic degradation, a derivative, 15-methyl PGE2 (15-E2) which is more slowly degraded than the natural compound was injected intravenously (i.v.) at various dose levels or into the third ventricle (3rd V) of ether-anesthetized, ovariectomized, estrogen (OVX, Eb)-treated rats and its effect on gonadotropin release was compared with that of PGE2. Both PGs injected i.v. were equally effective in increasing plamsa LH and maintaining the elevated levels, although 15-E2 induced a larger and more sustained increase in plasma FSH than PGE2. By contrast, 3rd V PGE2 was clearly more effective than 3rd V 15-E2 in releasing LH and to a lesser extent, FSH. The effect of 15-E2 on LH was similar to that produced by 3rd V PGE1, injected at a similar dose. However, its effect on FSH was greater than that of PGE1. To evaluate the effect(s) of prostaglandins of the A and B series on gonadotropin release, PGA1, PGA2, PGB1 or PGB2 were injected intraventricularly in OVX, Eb-treated rats. PGBs were injected into conscious, free-moving rats. PGA2 or PGB2 increased plasma LH concentrations although much less effectively than PGE2. Third V PGA1 or PGB1 were ineffective. The 3rd V injection of two cyclic esters (U-44069 and U-46619), stable analogs of the PG endoperoxide PGG2 and PGH2, induced a small, transient increase in LH levels and did not alter plasma FSH in conscious, free-moving animals. PGE2 injected intraventricularly at a similar dose was demonstrated to be mcuh more potent than the analogs in stimulating LH and FSH release. The results indicate that: 1) 15-E2, in spite of its described long-lasting activity, does not appear to be more potent than the natural compound in releasing LH, although when injected i.v., it appeared to induce a more sustained increase in plasma FSH; 2) although PGA2 and PGB2 can also act centrally to stimulate LH release, their low potency suggests that this is a pharmacological effect; and 3) the two analogs of PG endoperoxides tested proved to be poor stimuli for gonadotropin release. The significance of these findings is discussed.