Characterization and expression of different pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide receptors in rat ovarian follicles

Abstract

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 (PAC 1 -R), which binds specifically to both PACAPs and vasoactive intestinal polypeptide (VIP), although with lower affinity, and two VIP receptors, VPAC 1 -R and VPAC 2 -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 PAC 1 -R and VPAC 2 -R were expressed in granulosa cells, whereas only VIP receptors were expressed in theca/interstitial (TI) cells and fully grown oocytes presented only PAC 1 -R. The distribution of the VIP receptors was confirmed by immunofluorescence. HCG treatment induced stimulation of PAC 1 -R in granulosa cells and VPAC 2 -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 dosedependently 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.

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

“…In the rat ovary, where PACAP and PAC1-R (Gras et al 1996, Scaldaferri et al 1996, Koh et al 2000, Park et al 2000, Vaccari et al 2006 are transiently produced by gonadotrophin-stimulated preovulatory follicles, PACAP stimulates various ovarian functions, including cAMP accumulation, steroidogenesis and plasminogen activator (PA) production in cultured granulosa cells (Zhong & Kasson 1994, Gras et al 1999, Apa et al 2002. In addition, it accelerates meiotic maturation in rat cumulus-enclosed oocytes (Apa et al 1997) and inhibits apoptosis in preovulatory follicles (Lee et al 1999, Vaccari et al 2006.…”

A decrease of sensitivity of adenylyl cyclase and heterotrimeric g-proteins to chorionic gonadotropin and peptide hormones action in the tissues of reproductive system of the rats in the condition of experimental type 2 diabetes

“…Оба этих гормона, хотя и способны активировать различные сигнальные пути, большинство своих регуляторных эффектов реализуют через АЦС [15,17,19,20]. Нами показано, что PACAP-38 оказывает стимулирующее влияние на активность АЦ и GTP-связывание G-белков во всех исследованных тканях контрольных крыс, причем его эффекты, как и в случае ХГЧ, наиболее выражены в яичниках и тестикулах (рис.…”

“…Вследствие этого, обнаруженное нами снижение чувствительности АЦС к гормону в тканях репродуктивной системы крыс с диабетом 2-го типа может быть одной из основных причин, вызывающих нарушения регулируемых PACAP функций организма, к которым относятся контроль созревания ооцитов, ингибирование апоптоза фолликулов, регуляция синтеза и секреции стероидных гормонов [17,20,25,26].…”

“…Изучали влияние хорионического гонадотропина человека (ХГЧ), являющегося структурным и функциональным гомологом лютеинизирующего гормона (ЛГ), и пептидных гормонов релаксина, PACAP (Pituitary Adenylyl Cyclase-Activating Polypeptide) и соматостатина на функциональную активность АЦС в яичниках, тестикулах и матке диабетических крыс в сравнении с контрольными животными. Следует отметить, что ХГЧ, релаксин и PACAP действуют на активность аденилатциклазы (АЦ) в тканях репродуктивной системы в основном через G s -белки, в то время как соматостатин -через G i -белки [15][16][17][18][19][20].…”

Luteinizing Hormone-stimulated Pituitary Adenylate Cyclase-activating Polypeptide System and its Role in Progesterone Production in Human Luteinized Granulosa Cells

“…on the basis of sequence similarity, PACAP is the latest member of the secretin/glucagons/ vasoactive intestinal peptide (VIP) family of peptides [3]. PACAP exerts its action by binding to three types of g-protein-coupled seven transmembrane PACAP receptors: PACAP type I receptor (PAC 1 -R), which preferentially binds to PACAP and with lower affinity to VIP [4,5], and two others (VPAC 1 -R and VPAC 2 -R), which bind to PACAP and VIP with equally high affinity [5,6]. PAC 1 -R is coupled to both the adenylate cyclase and phospholipase C pathways while VPAC 1 -R and VPAC 2 -R are coupled only to the adenylate cyclase pathway [6].…”