Publication Date


Document Type


Committee Members

David Cool (Advisor)

Degree Name

Master of Science (MS)


Endocrine glands secrete peptide hormones that bind to specific receptors, and elicit a response. In the pituitary, prohormone convertases (PC) PC1/3 and PC2 convert inactive prohormones into biologically active peptide hormones. Proopiomelanocortin (POMC) is a precursor molecule that proteolytically cleaves at paired basic residue sites, and produces smaller biologically active peptides, such as adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), and β-endorphin. β-endorphin is an endogenous opioid peptide hormone that plays a vital role in the body's physiological response to stress, fear, and anxiety. Morphine is an exogenous opioid, used for the treatment of moderate to severe pain and competes with β-endorphins when binding to mu-receptors located on the surface of target cells. Opioids have a high abuse potential leading to the development of tolerance and dependence. The purpose of this research is to analyze the effects of morphine on prohormone processing by examining the β-endorphin peptide hormone spectrum using a Protein Chip Array technology with Surface Enhanced Laser Desorption Ionization Time of Flight Mass Spectrometry (SELDI- TOF-MS). Brain extracts (amygdala, nucleus accumbens, periaqueductal gray, lateral hypothalamus, arcuate nucleus, and paraventricular nucleus) from normal rats (n= 4-6) treated with morphine (75mg/day) or placebo pellet for 24 hours or a seven day treatment were examined in this study. The protein (1ug/uL) was applied to a Weak Cation Exchange (WCX2) ProteinChip, air-dried, and coated with alpha-cyano-4-hydroxy cinnamic acid (CHCA) matrix. SELDI-TOF MS (Ciphergen, LaJolla, CA) was used to analyze the peptide hormone spectrum for changes in peptide expression or processing levels. The results showed that morphine modulates β-endorphin processing at 7 days. Previous studies have shown that PC2 enzyme is primarily responsible for processing β-endorphin1-31 in mice. We conclude that PC2 is down-regulated, which may play a role in regulating the amount of active hormone to prohormone. This process may help the organism maintain homeostasis.

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Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded