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Gene Expression of Proprotein Convertases in Individual Rat Anterior Pituitary Cells and Their Regulation in Corticotrophs Mediated by Glucocorticoids

Département de Pharmacologie, Faculté de Médecine and Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4

Address all correspondence and requests for reprints to: Robert Day, Ph.D., Department of Pharmacologie, Faculté de Médecine, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, 3001, 12^e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4. E-mail: rday{at}courrier.usherb.ca

The subtilisin-like proprotein convertases (SPCs) are a family of serine proteinases that process secreted proteins at single or paired basic residues. Each SPC has been localized in the rat anterior pituitary, implying their importance in precursor processing in this tissue. The cellular distribution of each SPC has not been established in each hormone-producing cell type. We used double labeling in situ hybridization histochemistry to examine the mRNA distribution of five SPCs in relation to corticotrophs, thyrotrophs, lactotrophs, gonadotrophs, and somatotrophs. Our data demonstrated that SPC expression patterns were distinct, with each SPC expressed in more than one cell type. We noted that overlapping SPC expressions were the rule rather than the exception, suggesting potential SPC redundant functions. We examined the effects of adrenalectomy on corticotroph SPC expression. Most corticotrophs expressed SPC1, SPC3, and SPC4, but few corticotrophs expressed SPC2 or SPC6. After adrenalectomy, we observed increased mRNA levels for SPC1, SPC3, SPC4, and SPC6, but not for SPC2, in POMC-positive anterior pituitary cells. These increased levels were reversed by dexamethasone treatment. These data demonstrate the plasticity of SPCs expression in corticotrophs. SPCs may be directly involved in the mammalian stress response and may be important in hypothalamic-pituitary-adrenal axis homeostasis.