Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPACI receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.

Regulation of Growth Hormone Release in Common Carp Pituitary Cells by Pituitary Adenylate Cyclase-Activating Polypeptide: Signal Transduction Involves cAMP- and Calcium-Dependent Mechanisms

“…Using Nothern blot and RT-PCR, transcripts of PAC-1 receptors have been located in the goldfish pituitary, confirming that PACAP stimulates GH release in fish via activation of pituitary PAC-1 receptors [for a recent review, see ref. 28]. Recently, PACAP-stimulated GH release has been reported in turbot, a phylogenetically recent teleost [42].…”

“…goldfish and European eel), it has been postulated that PACAP may serve as a GH-releasing factor in fish through activation of pituitary PAC-1 receptors [for review, see ref. 28]. Owing to a general lack of information on the biochemical properties of PACAP receptors in lower vertebrates, the postreceptor signaling mechanisms mediating PACAP-stimulated GH release in fish are still unknown.…”

“…The a.a. sequences of these fish PAC-1 receptors are highly homologous to that of mammals. In the goldfish, mRNA transcripts of PAC-1 receptors can be identified in the pituitary [28]. Functional expression of goldfish PAC-1 receptors in COS-7 cells has revealed that these receptors are functionally coupled to cAMP synthesis [27].…”

Evidence of a reproduction-related function for pituitary adenylate cyclase-activating polypeptide-related peptide in an Anabantidae fish

“…The key regulators of reproduction at the pituitary levels are the gonadotropins. The effect of PACAP on gonadotropin release has been extensively studied in several teleosts, among them, the blue gourami (Levy et al 2010), tilapia (Vaudry et al 2009), and goldfish (Wong et al 2000). However, the possible effect of PRP on gonadotropin regulation in fish remains obscure.…”

Pituitary Adenylate Cyclase Activating Polypeptide and Neuropeptide Y Regulation of Gonadotropin Subunit Gene Expression in Tilapia: Role of PKC, PKA and ERK

“…Apart from GnRH, which is the major regulator of the gonadotropes, the pituitary adenylate cyclase-activating polypeptide (PACAP) and neuropeptide Y (NPY) are of particular importance. These peptides were found to act as gonadotropin secretagogues in mammals [4, 5, 6]and in teleosts [7, 8]. Although conveyed directly by hypothalamic nerve fibers, the principal effects ascribed to these peptides in fish are GnRH release and GnRH-induced LH release, while evidence for their direct effects on the pituitary cells is rather scarce [2, 5].…”