Different Gonadotrophin Releasing Hormone response sites in ovarian and pituitary cells in rat.

MONGIAT LA; LUX-LANTOS VA; LIBERTUN C

New Orleans, USA

Congreso; Endocrine Society, 86th Annual Meeting; 2004

Endocrine Society

The existence of two GnRH systems in several mammalian species suggests that both GnRH-I and GnRH-II may play important roles as endocrine/autocrine/paracrine regulators of reproductive function. However, in rodents as rat or mouse, there is no clear evidence about the existence of a GnRH system different from the GnRH-I/type I GnRHR. Previously, we demonstrated that GnRH-II acts in rat pituitary inducing LH and FSH secretion, similar to GnRH-I (1). Here we investigated the participation of type I GnRHR on GnRH-II-induced gonadotropin secretion and second messenger mobilization in anterior pituitary cells. Furthermore, we extended the study of GnRH-II effects on ovarian cells. GnRH-I and GnRH-II  (10-6M and 10-8M) stimulated IP3 production in cultures from 12 day-old female rat pituitary cells. Likewise, these cells release LH and FSH to the culture media after stimulation with GnRH-II in a dose-response way and in a GnRH-I-like manner. The GnRH analog 135-18 (agonist for type II GnRHR and antagonsit for type I GnRHR) was unable to elicit any cellular response tested in these pituitary cells (IP3 or gonadotropins release). GnRH-II responses were blocked by type I GnRHR antagonists, Cetrorelix or 135-18, suggesting that these effects were mediated by type I GnRHR. Cell cultures from adult mates rat pituitaries showed similar patterns for IP3 production and gonadotropins secretion. On the other hand, in super-ovulated (SPO) ovarian cells, GnRH-II and 135-18were unable to elicit an IP3 response, whereas GnRH-I (10-6M) induced a rise in IP3 levels which was blocked by 135-18 (10-6M).    Both GnRH-II as well as GnRH-I presented an anti-prolifferative effects on these ovarian SPO cells after 72 hours incubation ( 10-7 and 10-5M). Surprisingly, 135-18 at 10-7M showed a stronger anti-prolifferative efeect than the GnRH peeptides. However this action of 135-18 was abolished when this compond was used at 10-5M. Moreover, the analog 135-18 (10-7M), but neither GnRH-I nor GnRH-II, increased progesterone secretion (normalized by cell number) in SPO ovarian cells. Our results strongly suggest that GnRH-II is able to stimulate rat pituitary cells through the type I GnRHR with no evidences of the precence of a type II receptor. On the other hand, evidences indicate that there is a putative GnRHR in rat SPO ovarian cells whith different response chatacteristics from the GnRHR in pituitary. (1) Montaner et al., Neuroendocrinology 74:202-212, 2001.