EFFECTS OF NEUROMEDIN-U (NMU)-8 ON THE RAT HYPOTHALAMO-PITUITARY-ADRENAL AXIS - EVIDENCE OF A DIRECT EFFECT OF NMU-8 ON THE ADRENAL-GLAND

A 6-day subcutaneous (s.c.) treatment of adult rats with NMU-8 (1.5 or 6 mug/100 g/day) increased the average volume of zona fasciculata cel ls and decreased the number of zona reticularis cells in the adrenal c ortex. The lower dose of NMU-8 did not change blood ACTH concentration and adrenal weight, but it notably enhanced serum corticosterone leve l and basal corticosterone output by adrenal slices. ACTH blood level increased after ether stress in both control and NMU-8-treated rats, b ut stress-evoked rise in serum corticosterone was observed only in con trol rats. The higher dose of NMU-8 increased the level of circulating ACTH; however, it decreased adrenal weight and had no effect on serum corticosterone concentration and basal corticosterone output by adren al slices. NMU-8 (10(-10)/10(-6) M) did not affect basal and ACTH-stim ulated corticosterone yield by isolated adrenocortical cells, nor did it change their cytosolic Ca2+ concentration. NMU-8 (10(-8) M) markedl y raised basal corticosterone secretion by adrenal slices (including c ortex and medulla); higher concentrations of NMU-8 (10(-7)/10(-6) M) w ere ineffective on basal corticosterone secretion, but strongly inhibi ted the response to ACTH stimulation. On the ground of these findings it seems reasonable to suggest that NMU-8 exerts a biphasic effect on the function of the peripheral branch of the hypothalamo-pituitary-adr enal axis in rats: NMU-8 at low doses directly stimulates the function and growth of the adrenal cortex, while at high doses exerts a direct inhibitory action. Our data also indicate that the effects of NMU-8 o n the adrenal cortex require the structural integrity of the gland, pr obably the presence of the zona medullaris.