Antide

The present study was designed to assess the participation of gonadotropin-releasing hormone (GnRH) in the display of estrous behavior induced by application of vaginal-cervical stimulation (VCS) and by the intracerebroventricular (icv) administration of progesterone and its ring A-reduced metabolites to ovariectomized (ovx), estradiol benzoate (E2B) primed rats. Icv injection of Antide, a GnRH-1 receptor antagonist, significantly depressed lordosis behavior in ovx, E2B-primed rats treated with icv GnRH. Application of VCS to ovx, E2B-primed rats facilitated both lordosis and proceptivity. These behavioral responses were significantly depressed by the icv administration of Antide. Similarly, icv Antide blocked the stimulatory effect on both lordosis and proceptive behaviors elicited by progesterone and its ring A-reduced metabolites: 5alpha-pregnandione (5alpha-DHP), 5alpha-pregnan-3alpha-ol-20-one (5alpha,3alpha-Pgl) and 5beta-pregnan-3beta-hydroxy-20-one (5beta,3beta-Pgl) in ovx, E2B-primed rats.

An adequate vascular supply is important to provide endocrine and paracrine signals during follicular development. We evaluated the direct in vivo effects of both the GnRH-agonist Leuprolide acetate (LA) and the GnRH-antagonist Antide (Ant) on the expression of VEGF-A and ANPT-1 and their receptors in ovarian follicles from prepubertal eCG-treated rats. We also examined whether the changes observed in apoptosis by GnRH-I analogs have an effect on the caspase cascade. LA significantly decreased the levels of VEGF-A, its receptor Flk-1, and ANPT-1 when compared to controls, while the co-injection of Ant interfered with this effect. No changes were observed in the levels of Tie-2 after treatment with these analogs. When we measured the follicular content of caspase-3 protein, we observed that LA significantly increased the level of the active form. The co-injection of Ant interfered with this effect and Ant alone significantly decreased caspase-3 cleavage.

BACKGROUND/AIM: Protein kinase C (PKC) is a family of isoenzymes playing a key role in the regulation of gonadotrope cell functions. Specific PKC isoforms are activated and downregulated differentially by gonadotropin-releasing hormone (GnRH) and the phorbol ester TPA. In the present study, focusing mainly on PKC epsilon, the mechanisms underlying the proteasome-dependent downregulation of GnRH-activated PKC epsilon and TPA-sensitive PKC alpha and epsilon isoenzymes were investigated in alphaT3-1 gonadotrope cells.

In our previous studies, we demonstrated that ERK1/2 (extracellular signal-regulated protein kinase) and p38 MAPK (mitogen-activated protein kinase) are required for gonadotropin-releasing hormone (GnRH)-II-induced anti-proliferation of ovarian cancer cells. In the present study, we examined the role of the GnRH-I receptor, as well as the activation of protein kinase C (PKC), in the anti-proliferative effect induced by GnRH-I or II in ovarian cancer cells. Our results demonstrated that Antide, a GnRH-I antagonist, reversed the activation of ERK1/2 induced by GnRH-I or II and abolished the anti-proliferative effect of GnRH-I and II in ovarian cancer cells. Transfection of short-interfering RNA to abrogate the gene expression of the GnRH-I receptor reversed GnRH-I and II-induced anti-proliferation. These results indicate that GnRH-I or II induce anti-proliferation through the GnRH-I receptor in ovarian cancer cells. In addition, the activation of ERK1/2 by GnRH-I or II was mimicked by phorbol-12-myristate 13-acetate, a PKC activator.