Studies on the control of prostaglandin production by the hypothalamus in relation to LH release in the rat.

Prostaglandin (PG) and thromboxane (TX) synthesis by homogenates of the hypothalamus of rats has been measured in relation to the preovulatory surge of LH. Prostaglandin and TX production by the median eminence (ME) was five to ten times higher than that by the anterior hypothalamus/preoptic area (AH-POA). Prostaglandin E2 and PGF2 alpha were the major prostaglandins synthesized by the ME and AH-POA respectively. During the 4-day oestrous cycle, the PG- and TX-synthesizing capacity of the ME showed daily changes, being high at 06.00 and 22.00 h and, with the exception of pro-oestrus, low at 18.00 h. There was an additional peak of PGE2 production by the ME at 18.00 h on pro-oestrus coincident with the preovulatory LH surge. Progesterone treatment stimulated PGE2 synthesis by the ME of long-term ovariectomized, oestradiol-primed rats but not by the ME of acutely ovariectomized, oestradiol-primed rats. 2-Hydroxyoestradiol had no effect on PG and TX production by the ME at 18.00 h on dioestrus or 18.00 h on pro-oestrus. Noradrenaline stimulated PG and TX synthesis by the ME at the former time but not at the latter time. Prostaglandin F2 alpha-synthesizing capacity of the AH-POA peaked at 22.00 h on each day of the 4-day cycle. There was also an additional peak at 14.00 h on each day except dioestrus. Similar peaks occurred in the production of PGE2 and TXB2, except on pro-oestrus when the production of each compound remained low. There was no association between increased PGE2 production by the AH-POA and the preovulatory surge of LH. Noradrenaline, but not 2-hydroxyoestradiol, stimulated PG and TX production by the AH-POA at 18.00 h on both dioestrus and pro-oestrus. Progesterone stimulated PGE2, PGF2 alpha and 6-oxo-PGF1 alpha production by the AH-POA of acute, ovariectomized, oestradiol-primed rats but not of long-term ovariectomized, oestradiol-primed rats. Flurbiprofen, a cyclo-oxygenase inhibitor, prevented the preovulatory LH surge in two rats and delayed the LH surge by 2 h in four rats. It also reduced PG and TX production by the ME and AH-POA. Overall, the present studies show that there is an increase in PGE2-synthesizing capacity of the ME at the time of the preovulatory LH surge in the rat, and that the administration of an inhibitor of prostaglandin synthesis interferes with the timing of the LH surge.