Modulatory actions of progesterone on gonadotropin-releasing hormone-induced arachidonic acid liberation from perifused rat pituitary cells.

The stimulatory action of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion from cultured rat pituitary cells is modulated by estradiol and progesterone. Recent studies provided evidence that both steroids exert effects on different pathways of GnRH signal transduction, which might be responsible for their actions on luteinizing hormone (LH) release. Here we investigated whether the steroids are able to modulate GnRH-induced liberation of arachidonic acid, which is thought to be involved in GnRH signal transduction. Pituitary cells obtained from female rats were treated for 48 h with vehicle, 1 nmol/l estradiol or 1 nmol/l estradiol + 100 nmol/l progesterone, 48 h with 1 nmol/l estradiol and 2 h with 100 nmol/l progesterone. In addition, these cells were prelabeled with [3H]arachidonic acid. Then the cells were transferred to a perifusion system and challenged with a 6-min pulse of 100 nmol/l GnRH. Estradiol treatment enhanced the LH secretory response while GnRH-induced [3H]arachidonic acid liberation remained unaffected. However, progesterone modulated both LH secretion and [3H]arachidonic acid release in response to the GnRH stimulus. The short-term progesterone treatment paradigm enhanced the LH and arachidonic acid responses by up to 160 +/- 13 and 204 +/- 18%, respectively, while long-term treatment was inhibitory (59 +/- 9 and 63 +/- 4% vs control). Because arachidonic acid has been shown to be involved in GnRH signal transduction, it seems reasonable to speculate that the actions of progesterone described in the present study are related to its modulatory effect on GnRH-induced LH secretion.