Neuromedin-U inhibits unilateral adrenalectomy-induced compensatory adrenal growth in the rat

Neuromedin-U (NMU) is a brain–gut peptide, which has been previously found to stimulate hypothalamic–pituitary–adrenal axis in the rat and to control the growth of the rat adrenal cortex. The present study aimed to investigate the possible involvement of NMU in the regulation of unilateral adrenalectomy-induced compensatory adrenal growth, a phenomenon known to be neurally mediated. The right adrenal gland of mature female rats was removed, the contralateral gland was then analyzed at 24 and 72 h following surgery. Groups of rats were given 3 subcutaneous injections (24, 16 and 8 h before decapitation) of NMU8 (1.5 or 3.0 nmol/100 g/per injection). Three hours before sacrifice all rats received an intraperitoneal injection of 0.1 mg/100 g body weight of vincristin. By means of RT-PCR the presence of NMUR1 mRNA was detected in adrenal cortex of both intact and hemiadrenalectomized rats. As expected, unilateral adrenalectomy-induced an increase in adrenal weight, associated with increased plasma ACTH, aldosterone and corticosterone levels. The administration of NMU to hemiadrenalectomized rats did not significantly affect these parameters. NMU administration, however, notably inhibited the unilateral adrenalectomy-induced adrenocortical cell proliferation in both zona glomerulosa and zona fasciculata, as assessed by the metaphase index and the number of parenchymal cell nuclei per unit area of the tissue. When compared to hemiadrenalectomized animals receiving saline, a significant decrease of blood corticosterone levels was observed after 24 h in rats treated with the highest dose of NMU. Since these effects were independent on changes in blood ACTH, they could reflect an interaction of NMU with the neural system innervating the adrenal gland.