The Role of PACAP In Gonadotropic Hormone Secretion at Hypothalamic and Pituitary Levels

Abstract

The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its mRNAin the three levels of the hypothalamo-hypophyseal-ovarian axis was previously demonstrated using immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR). In the hypothalamus, PACAP is present in neuroendocrine effector cells and in the median eminence. In the anterior pituitary and ovary, PACAP is transiently present during the proestrous stage of the estrous cycle. In the pituitary, PACAP was observed in gonadotropes. In the ovary, PACAP was demonstrated in the granulosa cells of the preovulatory ovarian follicles. The effect of PACAP on luteinizing hormone (LH) secretion was demonstrated in in vivo and in vitro models. In our work we have studied the role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels. At the hypothalamic level, PACAP, administered intracerebroventricularly to female rats before the critical period of the proestrus stage, can inhibit LH release and ovulation. Its inhibiting effect is mediated through corticotropin-releasing factor (CRF) and endogenous opioids. PACAP administered to neonatal female rats delayed the onset of puberty by influencing the luteinizing hormone-releasing hormone (LHRH) neuronal system. In the pituitary gland, the release of PACAP depended on the stage of the estrous cycle and on the time of day the animals were sacrificed. On the day of proestrus, the number of PACAP-releasing cells showed a diurnal change with two peaks (in the morning and in the evening). The peak was much higher in the evening at the end of the LH surge than in the morning.

Changes in the Expression of Pituitary Adenylate Cyclase-Activating Polypeptide in the Human Placenta during Pregnancy and Its Effects on the Survival of JAR Choriocarcinoma Cells

“…PACAP occurs in two forms: 27 and 38 amino acid residues. Several subsequent studies have shown the role of PACAP not only in the regulation of pituitary hormone secretion but also in other reproductive functions (Counis et al 2007;Isaac and Sherwood 2008;Koves et al 2003;Sherwood et al 2007;Szabo et al 2002). PACAP is present in the uterus, where it supposedly plays a role in muscle contraction and blood supply (Steenstrup et al 1996).…”

Androgen Receptor Drives Transcription of Rat PACAP in Gonadotrope Cells

“…PACAP modulates gonadotropin biosynthesis and secretion, acting both alone and in concert with GnRH. Although less potent than GnRH, PACAP has been demonstrated to increase secretion of LH, FSH, and free ␣-subunit by perifused primary pituitary cells (5)(6)(7). The stimulatory effects of PACAP on LH secretion have been confirmed in vivo (8).…”

“…PACAP and its receptors are expressed in multiple tissues, including the central and peripheral nervous systems, smooth muscle of the lung and intestinal tract, and endocrine organs such as the placenta, adrenal, parathyroid, and endocrine pancreas; however, it is found most abundantly within the hypothalamic-pituitary-gonadal (HPG) axis (3,4). Reproductive functions include modulation of gonadotropin biosynthesis and secretion within the anterior pituitary gland, both alone and in concert with GnRH, as well as regulation of gonadal development and function (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

“…In support of this notion is that central injection of this peptide into male rat hypothalamus provoked an increase mRNA levels of gonadotropin-releasing hormone (GnRH) and somatostatin (SS) in the periventricular nucleus [164]. It was also observed that administration of PACAP into neonatal female causes a delay in puberty whereas central injection of the peptide into female rat before a critical period of proestrus stage controls ovulation via CRF and endogenous opioids [165]. In addition, PACAP through PAC1-R may play to regulate GnRH synthesis by the stimulatory feedback of progesterone [166].…”