Professor Office: North Wing N437 Phone:(601) 984-1604 E-mail: RKramer@umc.edu
The underlying theme of research in my laboratory is the control of cytochrome P450 enzymes. One focus within this theme is the regulation of cytochromes P450 within the adrenal cortex in relation to steroid hormone secretion. General aspects of adrenocortical function encompassed within that focus include the mechanisms of signal transduction for ACTH, angiotensin II and potassium; modulation of aldosterone secretion by factors such as extracellular pH, sodium ion concentration and osmolality, particularly in relation to the role of calcium in the steroidogenic actions of these agonists; regulation of the synthesis and activities of steroidogenic cytochromes P450, and differential control of adrenal androgen secretion.
The roles of cytosolic and mitochondrial calcium in the transduction mechanisms of angiotensin and potassium are being examined in relation to the activation of mitochondrial cholesterol side chain cleavage and aldosterone synthase. The interactions between changes in cytosolic calcium, hydrogen and sodium ion concentrations in the regulation of mitochondrial hydroxylases is also an area of investigation. A second focus is the effect of organophosphorus insecticides on the development of hepatic cytochrome P450 systems. Objectives within this focus are to determine if the fetal/neonatal liver metabolizes agricultural chemicals such as methyl parathion, chlorpyrifos, and diquat; to identify the specific isozymes of cytochrome P450 involved; to define changes in the expression and activities of specific cytochrome P450 isozymes as well as the mechanisms involved; and, finally, to determine the consequences of such actions in adulthood.
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