Table 1.
Endocrine changes with PACAC genetic manipulation
| Reproductive Function | ||
|---|---|---|
| PAC1R-KO | Disrupted estrus cycle | Jamen, 2000 (38) |
| PACAP-KO | Testosterone deficient with LH insufficiency | Lacombe, 2006 (37) |
| Delayed testicular aging | Lacombe, 2006 (37) | |
| Abnormal sperm shape and size | Brubel, 2012 (96) | |
| Sub-fertile females | Isaac, 2008 (36) | |
| Decreased progesterone and prolactin levels during pregnancy | Isaac, 2008 (36) | |
| Reduced uterine implantation rates | Shintani, 2002 (4) | |
| Lpr+ PMV neurons | Delayed female sexual maturation | Ross, 2018 (43) |
| Disruption of LH surge | Ross, 2018 (43) | |
| Low pup number per litter | Ross, 2018 (43) | |
| αGSU-PACAP | Delayed male sexual maturation | Moore, 2012 (1) |
| Lifelong suppressed gonadotropins | Moore, 2012 (1) | |
| glucose homeostasis | ||
| PAC1R-KO | Glucose intolerance | Winzell, 2007 (137) Persson, 2002(138) |
| impaired insulin secretion | Winzell, 2007 (137) | |
| Decreased glucagon secretion | Winzell, 2007 (137) Persson, 2002(138) |
|
| Less body wt & white adipose tissue Hypoinsulinemia | Tomimoto, 2008 (139) | |
| Increased insulin sensitivity | Tomimoto, 2008 (139) | |
| PACAP-KO | Microvesicular fat accumulation in | Gray, 2001 (140) |
| liver, skeletal muscle and heart increased triglycerides and cholesterol | Gray, 2001 (140) | |
| increased insulin and hypoglycemia | Gray, 2001 (140) | |
| impaired thermoregulation | Gray, 2002 (140) | |
| Susceptibility to insulin-induced hypoglycemia, and related death | Hamelink, 2002 (141) | |
| β-cell overexpression | Increased insulin secretion | Yamamoto, 2003 (142) |
| Improved insulin sensitivity in high fat diet-induced diabetes | Tomimoto, 2004 (143) Sakuri, 2012 (144) |
|
| Stress Response | ||
| PAC1R-KO | Reduced contextual fear conditioning | Otto, 2001 (145) |
| Impaired hippocampal long-term potentiation | Otto 2001 (146) | |
| PACAP-KO | Lack of stress-induced CRH upregulation | Agarwal, 2005 (112) |
| Disrupted stress-induced catecholamine release from splanchnic nerves. | Stroth, 2010 (147) | |
| Impaired stress-induced ACTH secretion | Stroth, 2010 (147) | |
| Reduced stress-induced corticosterone secretion | Stroth, 2010 (147) | |
| Impaired stress-induced adrenal steroidogenesis | Stroth, 2010 (147) | |
| Feeding Behavior | ||
| PAC1R-KO | Reduced POMC expression in the arcuate nucleus | Mounien, 2009 (148) |
| Increased postprandial ghrelin | Vu, 2015 (40) | |
| Decreased postprandial GLP-1, insulin and leptin | Vu, 2015 (40) | |
| Loss of PACAP-induced reduction in food intake | Vu, 2015 (40) | |
| PACAP-KO | Reduced carbohydrate intake | Nakata, 2004 (149) |
| Impaired leptin-stimulated adipose tissue sympathetic nerve activity | Tanida. 2013 (41) | |
| reduced food intake and body weight | Nakata, 2004 (149) | |
| reduced body weight | Gray, 2001 (140) | |