Cedarville University Research and Scholarship Symposium
Adrenal corticotropic hormone, or ACTH, is a peptide hormone secreted by the anterior pituitary gland. The full-length peptide is 39 amino acids long. ACTH signals through a G-protein linked receptor in humans, using the adenylyl cyclase pathway. Potassium and chloride channels have also been implicated in human ACTH signaling.
Tetrahymena thermophila are free-living, ciliated ptotozoans. These organisms exhibit avoidance behavior toward many polycationic peptides, which serve as chemorepellents. The reason for this is unknown; however, it is hypothesized that natural predators of T. thermophila secrete polycationic peptides, and that polycation avoidance allows T. thermophila to escape predation. We obtained a number of peptides derived from ACTH, including ACTH 1-39, ACTH 1-24, ACTH 11-24, ACTH 6-24, and ACTH 1-14. We hypothesized that the more highly charged peptide derivatives would be the most effective chemorepellents. This hypothesis was proven correct, with the most highly charged ACTH derivative, ACTH 6-24, demonstrated as the most effective chemorepellent. The least charged form of ACTH, ACTH 1-39, was least effective at causing avoidance.
We hypothesized that ACTH signaling in T. thermophila would use similar signaling pathways to those previously identified in humans. This, however, has not proven to be the case. We have tested G-protein inhibitors, adenylyl cyclase inhibitors, potassium channel blockers, and chloride channel blockers in T. thermphila. None of these drugs had any measurable effect on ACTH signaling. In addition, we have chelated extracellular calcium (using EGTA) and depleted ER calcium stores (using thapsigargin). Neither of these interventions inhibited ACTH signaling in this organism. Calcium channel blockers also failed to affect avoidance. This is highly unexpected, since all known chemorepellent pathways discovered in Tetrahymena to date are calcium-dependent. It is possible that ACTH is using a novel signaling pathway in T. thermophila. We hope that further testing will enable us to discover more about this signaling mechanism.
Baglio, A., Forsberg, J., McFarlane, D., Nichols, J., & Kuruvilla, H. (2012). ACTH: The Uninhibitable (or is it)? Cedarville University Research and Scholarship Symposium, Cedarville, Ohio.