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Pituitary adenylate cyclase activating polypeptide (PACAP) and growth hormone-releasing hormone (GHRH) are regulators of growth hormone secretion. In this article, we examined the difference in growth and mRNA expression of PACAP and GHRH between the sexes in half-smooth tongue sole, an important cultured fish species indicating sexually growth dimorphism in China. Firstly, a significant body weight difference between females and males was first observed at 7 months (P<0.05) and at 18 onths the mean body weight of the females (771.0±44.3 g) was as much as 4.9 times higher than that of males (130.6±6.0 g). As a result, half-smooth tongue sole, Cynoglossus semilaevis, is a good model to investigate the effects of growth-related genes expression on sexual growth dimorphism. Secondly, the cDNAs encoding PRP/PACAP and GHRH were isolated. Two differently processed mRNA transcripts of PRP/PACAP (PRP-encoding and PRP splice variant) were found. PACAP and GHRH mRNA was highly abundant in brain and less abundant in other tissues. However, PACAP mRNA was expressed in most brain regions, and was lower in the cerebellum. GHRH mRNA was predominantly expressed in the hypothalamus and weakly expressed in all areas of the brain examined. Ontogenetic expression analysis indicated that PACAP and GHRH mRNA was detected in the early stages of embryogenesis. Finally, differential expression showed that there was no significant difference of the expression level of PACAP or GHRH between the sexes before 8 months of age. However, between 9 and 12 months of age, the GHRH mRNA expression level in males was significantly higher than in females (P<0.05), which might be associated with GH deficiency in males. In contrast, the male PACAP mRNA expression level was not significantly higher than that in females even at 9 and 12 months of age. The present results provide important clues for understanding the sexual growth dimorphism mechanisms in half-smooth tongue sole.
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http://dx.doi.org/10.1016/j.ygcen.2010.09.011 | DOI Listing |
Biochem Pharmacol
September 2025
Section on Molecular Neuroscience, NIMH-IRP, Bethesda, MD, USA. Electronic address:
The PACAP receptor PAC1 is a G-coupled family B1 GPCR for which the highest-affinity endogenous peptide ligands are the pituitary adenylate cyclase-activating peptides PACAP38 and PACAP27, and whose most abundant endogenous ligand is PACAP38. PACAP action at PAC1 is implicated in neuropsychiatric disorders, atherosclerosis, pain chronification, and protection from neurodegeneration and ischemia. As PACAP also interacts with two related receptors, VPAC1 and VPAC2, highly selective ligands, both agonists and antagonists, for PAC1 have been sought.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Stress-related disorders, such as depression and anxiety, have been one of the most important medical issues. Accumulating evidence suggests that the activation of the pituitary adenylate cyclase-activating polypeptide and its receptor PAC1 are involved in the stress axis and the development of stress-related disorders. We recently developed PA-915, a small-molecule, non-peptide, high-affinity PAC1 antagonist, and demonstrated that it significantly suppresses anxiety-like behavior in acute stress-induced mice.
View Article and Find Full Text PDFBehav Neurosci
September 2025
University of Vermont, Department of Psychological Science.
Pituitary adenylate cyclase-activating polypeptide (PACAP, ) is a highly conserved neuropeptide that plays essential roles in numerous physiological functions, and central PACAP signaling has been associated with mechanisms regulating stress-induced psychopathologies. PACAP binds to several receptor subtypes, including PAC1 (), VPAC1 (), and VPAC2 (), to activate several signaling cascades that can alter neuronal excitability and enhance indices of neuroplasticity, and much of our prior work has suggested that the anxiogenic effects of bed nucleus of the stria terminalis (BNST) PACAP depend on the activation of PAC1 receptors. To complement our previous work that evaluated the roles of BNST PACAP expression and secretion in anxiety-related responses, we employed in the current work chemogenetic approaches in male PAC1-Ires-Cre mice to directly and specifically modulate the activities of BNST PAC1 receptor-expressing neurons.
View Article and Find Full Text PDFCephalalgia
August 2025
Bio Behavioral Health, Toms River, NJ, USA.
AimLY3451838 is a monoclonal antibody against pituitary adenylate cyclase-activating peptide (PACAP), a target in migraine research. The present study aimed to evaluate LY3451838 as a preventive treatment for participants with treatment-resistant migraine.MethodsFollowing preclinical assessment of LY3451838, including pharmacokinetic and pharmacodynamic studies, safety was evaluated in a phase 1 study of LY3451838 (n = 33) versus placebo (n = 13) in healthy participants.
View Article and Find Full Text PDFPsychoneuroendocrinology
October 2025
Department of Anesthesiology, Cancer Hospital affiliated Shanxi Medical University, Taiyuan, Shanxi 030000, China. Electronic address:
Traumatic brain injury (TBI) often leads to significant damage to the blood-brain barrier (BBB), contributing to the progression of neurological dysfunction and exacerbating inflammatory responses. BBB disruption is a critical factor in TBI pathology, as it facilitates neuroinflammation and edema, thereby worsening brain injury. For the first time, this study investigates the neuroprotective role of Human Pituitary Adenylate Cyclase Activating Peptide (PACAP) in mitigating the progression of TBI by addressing BBB dysfunction.
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