Expression and Regulation of Pituitary Adenylate Cyclase-Activating Polypeptide in Rat Placental Cells

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified as a hypophysiotropic factor that regulates pituitary cell functions and has been subsequently shown to be widely distributed and have multiple functions. The PACAP is known to be expressed in placental tissues and is suggested to have a critical role in physiological function of the placenta. In addition to PACAP, the hypothalamic peptides kisspeptin and gonadotropin-releasing hormone (GnRH) are also expressed in placental cells. In this study, we used primary cultures of placental tissues from rats of 16 to 18 days gestation and examined the regulation and function of PACAP. The PACAP messenger RNA (mRNA) expression and PACAP-immunoreactive cells were detected in primary cultures of rat placental cells. The PACAP mRNA expression in placental cells was upregulated in the presence of the sex steroids estradiol and progesterone; however, their combined treatment failed to enhance their individual effects. When the cells were stimulated with kisspeptin, PACAP mRNA expression was increased. Similarly, GnRH had a stimulatory effect on PACAP expression. Conversely, kisspeptin expression in placental cells was increased by PACAP stimulation, whereas PACAP failed to stimulate GnRH mRNA expression in these cells. Finally, we found that PACAP had a stimulatory effect on human chorionic gonadotropin expression in placental cells. Our current observations suggest that the hypothalamic peptides PACAP, kisspeptin, and GnRH are interrelated and maintain placental functions.

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

“…This finding is consistent with that reported by Horikoshi et al 9 However, a positive correlation between KP-10 and β-hCG was noticed during the 3rd trimester in PE women. A finding that was also noticed by other researchers Oride et al 10 who reported the stimulatory effect of kisspeptin on hCG mRNA expression in rat placental cells. Therefore, it is noteworthy that rapidly rising β-hCG concentrations during pregnancy suppress secretion of both LH and FSH by blunting the response to gonadotropin-releasing hormone (GnRH).…”

“…Likewise, expression of KP-10 mRNA has been observed to be augmented in both human and rat placenta. 9,10 High concentrations of KP-10 have been found in syncytiotrophoblasts, which secrete several hormones. This includes, human chorionic gonadotropin (hCG), placental growth hormone, estrogen (E2) and progesterone (PRG).…”

“…This includes, human chorionic gonadotropin (hCG), placental growth hormone, estrogen (E2) and progesterone (PRG). [10][11][12][13] The effect of KP-10 on luteinizing hormone (LH) surge, gonadotropin-releasing hormone and follicle stimulating hormone (FSH) secretion has been demonstrated in humans as well as in animal models. [14][15][16] Therefore, this study aimed to evaluate plasma KP-10 as a marker for PE and assess its relation to altered reproductive hormones in PE women.…”

Cross-genetic determination of maternal and neonatal immune mediators during pregnancy

“…We further identified one fetal locus associated with maternal sIL2R-α, ADCYAP1 , or PACAP , which encodes a signalling neuropeptide widely expressed in the central and peripheral nervous systems. PACAP is also expressed in different parts of the placenta and the umbilical cord where it affects cell survival, angiogenesis, and proliferation of trophoblast cells [ 58 ]. This locus was not associated with any fetal cytokine/chemokine, nor has it previously been associated with adult immune phenotypes [ 8 ].…”

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

“…The most likely option is that PACAP originates from the placenta because PACAP immunoreactive fibers innervate vessels in the uteroplacental unit in humans (151). PACAP38 and PAC1 mRNA has been demonstrated in the placenta as well as immunoreactive stromal and decidual cells in humans and rats (152)(153)(154)(155).…”