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Sergio Vaccari^*,, Stefania Latini^*, Marzia Barberi, Anna Teti¹, Mario Stefanini

Department of Histology and Medical Embryology, University of Rome ‘La Sapienza’, Via A. Scarpa, 14, 00161 Rome, Italy
¹ Department of Experimental Medicine, University of L’Aquila, Rome, Italy

(Requests for offprints should be addressed to R Canipari; Email: rita.canipari{at}uniromal.it)

^* (S Vaccari and S Latini contributed equally to this work)

(S Vaccari is now at Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive Stanford, CA 94305-5317, USA)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide transiently expressed in preovulatory follicles. PACAP acts by interacting with three types of PACAP receptors. PACAP type I receptor (PAC₁-R), which binds specifically to both PACAPs and vasoactive intestinal polypeptide (VIP), although with lower affinity, and two VIP receptors, VPAC₁-R and VPAC₂-R, which bind to PACAP and VIP with equal affinity. In the present study, we showed the expression of all three receptors in whole ovaries obtained from juvenile and gonadotropin-treated immature rats. A more detailed analysis on cells from preovulatory follicles showed that PAC₁-R and VPAC₂-R were expressed in granulosa cells, whereas only VIP receptors were expressed in theca/interstitial (TI) cells and fully grown oocytes presented only PAC₁-R. The distribution of the VIP receptors was confirmed by immunofluorescence. HCG treatment induced stimulation of PAC₁-R in granulosa cells and VPAC₂-R in TI cells. The presence of functional PACAP/VIP receptors was also supported by metabolic studies. We further evaluated the presence of PACAP and VIP receptors by testing the effect of these peptides on apoptosis in granulosa cells cultured, isolated or in whole follicles. Treatment of follicles with PACAP and VIP dose-dependently inhibited apoptosis, while only PACAP significantly inhibited isolated granulosa cells. These results demonstrate a different expression of PACAP/VIP receptors in the various follicle compartments and suggest a possible role for PACAP and VIP on granulosa and TI cells, both during follicle development and ovulation.

This article has been cited by other articles:

				M. Barberi, B. Muciaccia, M. B. Morelli, M. Stefanini, S. Cecconi, and R. Canipari Expression localisation and functional activity of pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal polypeptide and their receptors in mouse ovary Reproduction, August 1, 2007; 134(2): 281 - 292. [Abstract] [Full Text] [PDF]