The regulation of proenkephalin gene expression in non-neuronal tissues

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Biochemistry and Molecular Biology

First Committee Member

Michael H. Melner - Committee Chair


The regulation of non-neuronal proenkephalin gene expression was examined in a variety of different in vivo and in vitro model systems to obtain a better understanding of the mechanisms involved and to compare with the regulation of expression in neuronal systems.Proenkephalin gene expression is high in the proliferative endometria but undetectable in the secretory endometria. Detectable levels of proenkephalin gene expression were not observed in the endometria of ovariectomized macaques but were observed in estradiol-treated ovariectomized macaques. Proenkephalin gene expression was not observed in either the endometria of ovariectomized macaques treated with progesterone and estradiol or from decidual tissue during pregnancy. These observations suggest that expression of the proenkephalin gene in the non-human primate endometrium correlates with the proliferative state and is under regulation by steroid hormones.Neurotransmitter analogs and analogs of their putative second messengers stimulate proenkephalin gene expression in primary cultures of neonatal rat cerebral type-1 astrocytes by stimulating gene transcription, synthesis and secretion of proenkephalin-derived peptides. Additionally, tumor necrosis factor-$\alpha$ and interleukin-1$\beta$ increase proenkephalin gene expression in astrocytes by increasing the levels of transcripts and secreted peptides. Interestingly, the major form of proenkephalin-derived peptide secreted by astrocytes is the intact precursor polypeptide. These results implicate astrocytes as potentially capable of mediating neuroimmune interactions in the central nervous system subsequent to brain injury or during disease.The proenkephalin gene expression in primary cultures of neonatal rat cardiomyocytes is increased by neuropeptides, neurotransmitter analogs and analogs of their putative second messengers. Cardiac proenkephalin gene expression results in transcripts that are associated with polyribosomes and the synthesis and secretion of larger forms of the proenkephalin-derived peptides. The developmental programs of proenkephalin gene expression in skeletal and cardiac muscles appear to be dramatically divergent where during neonatal development gene expression decreases dramatically and increases respectively. Skeletal muscle-derived myoblasts induced to differentiate in vitro demonstrate decreased proenkephalin gene expression with differentiation.The non-neuronal expression of larger proenkephalin-derived peptides and the correlation between elevated proenkephalin gene expression with tissues that are either undifferentiated or possess the potential for rapid proliferation suggests a putative role for these larger peptides in development.


Biology, Molecular; Biology, Neuroscience

Link to Full Text


Link to Full Text