The proopiomelanocortin (pro ACTH/endorphin, POMC) peptide hormone system is of central importance in animal physiology in that it has a variety of endocrine functions as well as central nervous system functions. Because of the different functions of the POMC derived peptides, the expression of these peptide hormones is regulated in a complex fashion. In this research program, it is our aim to understand how the POMC gene is regulated in the many different cell types which express it. Specifically, we wish to examine in more detail the regulation of the POMC gene in the pituitary, building on our previous work. Using POMC cDNAs and genomic DNAs, we plan to identify at which levels (transcription, RNA processing, translation, or RNA stability) glucocorticoids, estrogens, corticotropin releasing factor, dopamine and norepinephrine act to control POMC production in the pituitary. In addition, POMC gene expression in the hypothalamus will be investigated using molecular biological methods which have been developed to deal with the extremely small number of POMC producing neurons in this tissue. using the Palkovits punch technique to isolate discrete hypothalamic regions and in situ hybridization histochemistry to study POMC mRNA in individual cells, we plan to identify those factors (steroid hormones, neurotransmitters, etc. as well as physiological stimuli such as stress) which modulate POMC mRNA levels and hopefully elucidate the mechanism of that modulation. Using similar techniques as well as organ culture the developmental pattern of POMC gene expression in the fetal rat will be studied. These studies will lead to a better understanding of how an important endocrine and neromodulatory peptide hormone system is regulated at the molecular level.
