Lipolytic response, cyclic AMP and cyclic GMP accumulation in rat adipocytes stimulated with ACTH: Effect of MtT-F4 tumor and clofibrate treatment

Abstract

A hyperlipidemia was induced in male Fisher rats by implantation for 31 days of a mammotropic tumor (MtT-F4) which secretes large quantities of ACTH, GH, and prolactin. Following stimulation of isolated adipose tissue cells with ACTH, the lipolytic response and the accumulation of cyclic AMP were higher in cells derived from the rats with the tumor, while the accumulation of cyclic GMP was not different from control adipocytes. Further, when the isolated adipose tissue cells were stimulated with dibutyryl cyclic AMP the lipolytic response was increased to the same extent in both control and tumor-bearing groups. Clofibrate treatment did not alter the increased lipolytic response though it partially decreased the accumulation of cyclic AMP following stimulation by ACTH in adipocytes derived from tumor-bearing rats. However, clofibrate treatment resulted in a significantly greater accumulation of cyclic GMP in fat cells stimulated with ACTH from both control and tumor-bearing rats. Clofibrate in the diet did not alter the levels of GH or prolactin in the control rats nor were the elevated hormone levels of the tumor-bearing rats changed. Thus the adipose tissue cells from fasted rats treated with clofibrate and treatment withdrawn 24 h prior to sacrifice did not exhibit a decrease in the lipolytic response to ACTH. However, the decrease in the accumulation of cyclic AMP and the increase in the accumulation of cyclic GMP observed may suggest an involvement of these nucleotides in the mechanism of action of clofibrate on the adipose tissue.