Stimulation of Prostaglandin Accumulation by Luteinizing Hormone-Releasing Hormone (LHRH) and LHRH Analogs in Rat Granulosa Cells in Vitro*

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Abstract
LHRH and LHRH agonists have been reported to exhibit somewhat paradoxical antireproductive effects. The current studies were undertaken to examine the actions of these substances on one parameter of ovarian function which is required for ovulation, i.e. prostaglandin production. Granulosa cells were obtained from immature rats 48 h after injection of 20 IU PMSG and incubated for up to 5 h in vitro. LHRH, [D-Ala6, des-Gly-NH210]LHRH-ethylamide (Analog I) and [D-Leu6, des-Gly-NH210]LHRH-ethylamide (Analog II) were observed to stimulate prostaglandin accumulation by granulosa cells. Analog I, for example, at 100 ng/ml increased PGE from 0.19 ± 0.06 in the control to 7.7 ± 2.01 ng/2 × 106 cells (n = 7; P < 0.01) after 5 h. TRH, on the other hand, had no effect on prostaglandin accumulation. When added with LH or FSH, the stimulation by maximal concentrations of Analog I and the gonadotropins appeared additive. Although the stimulation of prostaglandin accumulation by LH appears to be mediated by cAMP, no effect of Analog I on the amount of cAMP could be detected. cAMP was determined in cells plus medium at times of 1.5 min to 5 h and at concentrations of 10-2000 ng/ml Analog I, but did not change from the control. LHRH and LHRH agonists, therefore, stimulate the accumulation of ovarian granulosa cell prostaglandins and do so in a manner apparently distinct from that of LH or FSH.