NameGorelick-Feldman, Jonathan Isaac (author), Raskin, Ilya (chair), Simon, James (internal member), Giafagna, Tom (internal member), Cohick, Wendie (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionPhytoecdysteroids, polyhydroxylated ketosteroids, are the plant analogues of insect growth hormones. Although their role in insect molting is well characterized, their function in plants is less clear. Lacking the properties of classic plant hormones, phytoecdysteroids may be involved in plant growth and defense. One of the main benefits of phytoecdysteroids may be their therapeutic effects on mammals, including humans. Their claimed medicinal properties include anabolic, adaptogenic, hepatoprotective, and hypoglycemic activity. Although ethnobotanical use has been supported by some evidence, the research is quite limited, lacking the scientific rigor necessary to be convincing.
Two ecdysteroid containing plants, Ajuga turkestanica, and Spinacia olearaceae (Spinach), were selected as beneficial sources of phytoecdysteroids. Cultivation, analysis of ecdysteroid content, and characterization of anabolic activity were performed to support future medicinal use.
Phytoecdysteroids' anabolic activity, one of their most interesting properties due to the claimed lack of androgenic effect, was studied. Anabolic activity was confirmed in animal studies and a cellular model of skeletal muscle. The cellular model was used to characterize ecdysteroids' effect on protein incorporation and to elucidate the signal transduction pathway involved. Ecdysteroid's lack of androgenic activity was confirmed in vivo and in vitro, with ecdysteroids showing no specific binding to the androgen receptor.
Identification of mammalian nuclear receptors homologous with the insect nuclear ecdysone receptor led to binding and activation assays of potential receptors using ecdysteroids. The discovery of a lesser known membrane bound G Protein Coupled Receptor (GPCR) insect ecdysone receptor, DoEcR, suggested the existence of a hypothetical mammalian membrane bound GPCR ecdysone receptor.
Use of specific inhibitors supported the involvement of G protein signaling, Phospholipase C (PLC), Inositol Phosphate 3 Receptor (IP3R), and Akt. Ecdysteroid stimulated activation of Akt confirmed its role in the anabolic effect. Ecdysteroid generated increases in intracellular calcium were also characterized, with the rapid flux in Ca2+ linked with Akt activation and anabolic activity. The evidence produced suggests the involvement of a putative mammalian GPCR ecdysteroid receptor mediating the anabolic effect through the rapid activation of the PLC/IP3R pathway, generating Ca2+ flux which leads to activation of the Phosphoinositide 3 Kinase/Akt pathway, eventually causing increases in protein incorporation.
NoteIncludes bibliographical references (p. 131-142)
Noteby Jonathan Isaac Gorelick-Feldman
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.