Expression localisation and functional activity of pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal polypeptide and their receptors in mouse ovary

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) positively affect several parameters correlated with the ovulatory process. PACAP is transiently expressed in rat preovulatory follicles, while VIP is present in nerve fibres at all stages of development. These two peptides act by interacting with three types of receptors: PACAP type I receptor (PAC1-R), which binds with higher affinity to PACAP, and two VIP receptors (VPAC1-R and VPAC2-R), which bind to PACAP and VIP with equal affinity. The aim of the present study was to characterise the PACAP/VIP/receptor system in the mouse ovary. Results obtained by RT-PCR, immunohistochemistry and in situ hybridisation showed that PACAP was transiently expressed in granulosa cells of preovulatory follicles after human chorionic gonadotrophin (hCG) stimulation, while VIP mRNA was never observed. All the receptors were present in 22-day-old untreated mice. In preovulatory follicles, PAC1-R was expressed both in granulosa cells and in residual ovarian tissue but was stimulated by hCG mainly in granulosa cells; VPAC2-R was present in both the cell compartments and was only mildly stimulated; VPAC1-R was present mainly in the residual ovarian tissue and was downregulated by hCG. PACAP and VIP were equipotent in inhibiting apoptosis in granulosa cells, confirming the presence of functional PACAP/VIP receptors. The contemporary induction by hCG of PACAP and PAC1-R in granulosa cells of preovulatory follicles suggests that, also in mouse ovary, PACAP may play a significant role around the time of ovulation. Moreover, the presence of PACAP/VIP receptors in the untreated ovary suggests a possible role for PACAP and VIP during follicle development.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…In the rat ovary, most granulosa and cumulus cells from large preovulatory follicles contain both PACAP mRNA and PACAP-LI (Grä s et al, 1996). Human chorionic gonadotropin (hCG) induces a transient increase of both PACAP and progesterone receptor mRNA expression (Ko et al, 1999;Barberi et al, 2007). The peak of expression of progesterone receptor mRNA occurs 3 h after hCG treatment and the peak of PACAP mRNA only after 6 to 12 h, suggesting that progesterone receptor activation is required for PACAP gene expression (Ko et al, 1999;Sayasith et al, 2007).…”

“…Incubation of immature rat preovulatory follicles with PACAP or VIP induces a dose-dependent inhibition of follicle apoptosis (Flaws et al, 1995;Lee et al, 1999b), reduces cell proliferation promoted by FSH (Cecconi et al, 2004), and could be involved in the cyclic recruitment of immature follicles (Grä s et al, 2005). In luteinized granulosa cells, PACAP stimulates cAMP accumulation more potently than LH (Richards et al, 1995;Heindel et al, 1996), promotes survival (Barberi et al, 2007;Morelli et al, 2008), and increases plasminogen activator expression (Apa et al, 2002). In addition, neonatal administration of PACAP delays the first ovulation (Szabó et al, 2002).…”

Differential regulation of kit ligand A (kitlga) expression in the zebrafish ovarian follicle cells – Evidence for the existence of a cyclic adenosine 3′, 5′ monophosphate-mediated binary regulatory system during folliculogenesis

“…We also tested the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) as previous studies have shown that PACAP is stimulated by gonadotropins in the ovary (Barberi et al, 2007;Lee et al, 1999;Sayasith et al, 2007;Wang et al, 2003) and both LH and PACAP promote final oocyte maturation in mammals and fish through cAMP pathways (Apa et al, 1997;Wang et al, 2003;Zhou et al, 2011). Afterwards, we went on to focus the study on the intracellular signal transduction mechanisms that underlie hCG and PACAP actions with particular emphasis on the pathways downstream of cAMP including PKA and Epac pathways.…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…Furthermore, it serves important regulatory and protective roles in the gastrointestinal [49], cardiovascular [50][51][52], reproductive [53,54] and respiratory systems [55]. The effects of PACAP are mediated through three receptors: VPAC 1 (previously designated the VIP, VIP1 or PACAP type II receptor), VPAC 2 (known as the VIP2 or PACAP type III receptor) and PAC 1 (formerly known as the PACAP type I receptor); the latter has 1000-fold higher specific affinity for both forms of PACAP than for VIP [28,56].…”