STEROID REGULATION OF PEPTIDE SENSITIVITY IN THE CNS

Project: Research project

Description

Steroid hormones induce long-term changes in the form and function of the
nervous system. These changes are likely mediated via changes in the
genome. The aim of this project is to use the steroid regulation of a
peptide-mediated behavior of an insect, Manduca sexta, as a model for how
steroids can control the responsiveness of the CNS. The ecdysteroids are
steroid hormones which regulate the metamorphosis and molting of insects.
One of the final steps in the molting process is the shedding (ecdysis) of
the old cuticle. This behavior is triggered by the action of a
neuropeptide, eclosion hormone (EH). The peptide can only act on the CNS,
however, if the nervous system has been primed by exposure to the
ecdysteroids. Studies that I have carried out indicate that the ecdysteroids act at two
or more levels to regulate peptide responsiveness. Firstly on the
receptor/2nd messenger (cGMP) system and secondly, inducing the de novo
synthesis of two proteins (the EGPS) which are phosphorylated by the action
of the peptide. Only when both of these components are functional will the
nervous system respond to EH. The aim of this proposal is to examine the
steroid regulation of both of these steps in detail. Using radiolabeled EH
I will characterize the EH receptors and determine if they are up regulated
in response to ecdysteroids. I will also elucidate the pathway by which EH
elevates cGMP and ascertain if any element of this pathway is regulated by
the ecdysteroids. I believe that the de novo synthesis of the EGPs is the final step in
enabling the CNS to respond to EH. Once antibodies to the EGPs have been
generated I will be able to follow their synthesis, the synthesis of the
EGP mRNA(s) and their steroid regulation. Ultimately, I intend to isolate the steroid-regulated genes at each step in
the cascade of EH action. The information gained from this proposal will
be of importance to other studies in CNS plasticity which are believed to
be regulated at the level of the genome.
StatusFinished
Effective start/end date7/18/918/31/12

Funding

  • National Institutes of Health: $174,617.00
  • National Institutes of Health: $302,000.00
  • National Institutes of Health
  • National Institutes of Health: $264,110.00
  • National Institutes of Health
  • National Institutes of Health: $188,865.00
  • National Institutes of Health
  • National Institutes of Health: $51,381.00
  • National Institutes of Health: $269,500.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $269,500.00
  • National Institutes of Health
  • National Institutes of Health: $268,990.00
  • National Institutes of Health: $302,000.00
  • National Institutes of Health: $302,000.00
  • National Institutes of Health: $266,805.00
  • National Institutes of Health
  • National Institutes of Health: $302,000.00

Fingerprint

cyclic GMP
eclosion hormone
guanylate cyclase
Cyclic GMP
nervous system
ecdysteroids
steroids
peptides
synthesis
Nervous System
molting
oxygen
Neurotransmitter Agents
nitric oxide
Manduca
hypoxia
Manduca sexta
insect behavior
insects
steroid hormones

ASJC

  • Medicine(all)
  • Neuroscience(all)