Female reproductive functions of the neuropeptide PACAP

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated as a hypothalamic peptide. It has a widespread distribution in the body and has a diverse spectrum of actions. Among other processes, PACAP has been shown to be involved in reproduction. In this review we summarize findings related to the entire spectrum of female reproduction. PACAP is a regulatory factor in gonadal hormone production, influences follicular development and plays a role in fertilization and embryonic/placental development. Furthermore, PACAP is involved in hormonal changes during and after birth and affects maternal behavior. Although most data come from cell cultures and animal experiments, increasing number of evidence suggests that similar effects of PACAP can be found in humans. Among other instances, PACAP levels show changes in the serum during pregnancy and birth. PACAP is also present in the human follicular and amniotic fluids and in the milk. Levels of PACAP in follicular fluid correlate with the number of retrieved oocytes in hyperstimulated women. Human milk contains very high levels of PACAP compared to plasma levels, with colostrum showing the highest concentration, remaining steady thereafter for the first 7 months of lactation. All these data imply that PACAP has important functions in reproduction both under physiological and pathological conditions.

Effect of PACAP/PAC1R on Follicle Development of Djungarian Hamster (Phodopus sungorus) with the Variation of Ambient Temperatures

“…PACAP expression was positively correlated with the number of growing follicles and antral follicles (Figure 6A,B), and PAC1R was also positively correlated with the number of growing follicles (Figure 6C,D). Those results indicated that PACAP/PAC1R was commonly correlated with the follicle development, which is consistent with previous findings that PACAP/PAC1R is involved in regulating follicle development [27]. However, in this study, we found that PACAP/PAC1R is state-dependent for the follicle development.…”

“…In this pathway, PACAP uses the classical growth factor pathway to activate the expression of cFOS through MAPK phosphorylation of transcription factor ELK, and then activate FSH β [26]. Furthermore, PACAP and PAC1R may participate in the regulation of reproduction and follicle development via the HPO axis [27][28][29]. In studies, PACAP has been shown to inhibit FSH synthesis via the HPO axis to regulate reproduction [30].…”

Neuropeptide Signaling is Required to Implement a Line Attractor Encoding a Persistent Internal Behavioral State

“…Neuropeptides comprise a class of evolutionarily conserved 29,30 neuromodulators that control behavior-specific internal motive states associated with mating 31,32 , aggression [33][34][35] , social attachment 36 , feeding 37 and predator defense 38 , as well as other behaviors. Neuropeptides are well known to modulate synaptic strength and neural circuit properties such as patterns of oscillation [39][40][41] , but their role in implementing persistent activity and attractor dynamics has not been extensively studied in vertebrates.…”

Effects of the Neuropeptides Pituitary Adenylate Cyclase Activating Polypeptide and Vasoactive Intestinal Peptide in Male Fertility

“…The neuroendocrine system is responsible for regulating a number of functions in our body, including reproduction. Specifically, neuropeptides have been found to be involved throughout several phases of reproduction, from sexual behavior, conception, lactation, and parent-infant bonding, as their receptors are found throughout both the male and female reproductive tracts [7][8][9]. While most of the research investigated the role of numerous neuropeptides on female fertility and reproduction, there is evidence indicating their critical involvement in male fertility and sperm development [9][10][11].…”