Neuromedin U enhances proliferation of ACTH-stimulated adrenocortical cells in the rat

Abstract

Abstract. Neuromedin U (NMU) is a brain-gut peptide involved in the regulation of the hypothalamic-pituitaryadrenal axis and adrenocortical cell proliferation. In this study, we investigated the effects of NMU8 (three subcutaneous injections of 6.0 nmol/100 g, 24, 16 and 8 h before autopsy) on the adrenal glands of rats treated for 2 or 4 days with a low (2 μg/100 g body weight/24 h) or a high (8 μg) dose of adrenocorticotropic hormone (ACTH). As revealed by RT-PCR, ACTH treatment did not prevent expression of NMUR1 in rat adrenal cortex. At day 4 of ACTH administration, the weight of adrenals was lower than at day 2. NMU8 administration prevented ACTH-induced increases of adrenal weight at day 2 of the experiment. ACTH plasma concentrations were increased in all ACTH-administered rats. NMU8 administration increased ACTH plasma concentration at day 2 of the lower ACTH dose-treated group while it reduced the ACTH plasma level at day 4 in the higher ACTH dose-administered rats. In all groups of ACTH-treated rats, NMU8 changed neither aldosterone nor corticosterone plasma concentrations. In the zona glomerulosa (ZG), NMU8 increased metaphase index at days 2 and 4 in the lower ACTH dose-treated group and had no statistically significant effect in rats treated with the higher ACTH dose. In the zona fasciculata (ZF), NMU8 administration increased metaphase index at day 2 in the lower ACTH dose-treated group but reduced metaphase index at day 4 in the higher dose ACTHadministered rats. NMU8 reduced the number of cells per unit area both in ZG and ZF at day 2 in the higher ACTH dose-treated rats. In the remaining groups NMU8 did not produce statistically significant changes in the number of cells per unit area. Thus, our findings demonstrate that exogenous NMU may stimulate proliferation primarily of the cortical ZG cells in rats administered with ACTH, although at high doses of exogenous corticotropin an opposite effect occurred.

Neuromedins U and S involvement in the regulation of the hypothalamo–pituitary–adrenal axis

“…Moreover, in enucleation-induced adrenal regeneration NMU notably enhanced proliferative activity of adrenocortical cells (Trejter et al, 2008). A similar stimulating effect of sc administered NMU on proliferative activity (metaphase index) was seen in ACTH treated rats (Trejter et al, 2009). In contrast, in hemiadrenalectomized rats NMU notably inhibited adrenocortical cell proliferation in both zona glomerulosa and zona fasciculata, as assessed by the metaphase index (Malendowicz et al, 2009).…”

“…The stimulating effect of sc administered NMU on plasma corticosterone concentrations also was found in rats during enucleation-induced regeneration, as well as in rats treated with low ACTH doses (Trejter et al, 2008, 2009). On the other hand, NMU8 administration to immature rats was found to raise aldosterone, but not corticosterone concentrations (Ziolkowska et al, 2008).…”

“…Moreover, the presence of NMUR1 mRNA in isolated zona glomerulosa and fasciculata/reticularis cells rules out the possibility that the expression was due to the presence in the specimens assayed of the non-parenchymal components of the gland. Expression of NMUR1 as mRNA and protein was demonstrated in adrenal gland of intact rat, in enucleation-induced regenerating gland, in hemiadrenalectomized animals (compensatory adrenal growth) as well as in ACTH-stimulated one (Trejter et al, 2008, 2009; Malendowicz et al, 2009). …”

“…First reports demonstrated that a single sc injection of NMU8 resulted in a transient increase in ACTH blood concentration while after 2–6-day treatment (low NMU8 dose) blood ACTH level remained unchanged (Malendowicz et al, 1993, 1994b; Trejter et al, 2009). Only the higher dose of NMU8 (6 μg/100 g/day for 6 days) increased the level of circulating ACTH.…”

Neuromedins NMU and NMS: An Updated Overview of Their Functions

“…It should be noted that in the human adrenal gland, the highest density of 125I-NMU25 binding sites is observed in the zona glomerulosa and reticularis, and slightly lower in the zona fasciculata and medulla (19). Expression of NMUR1 as mRNA and protein was demonstrated in adrenal gland of intact rat, in enucleationinduced regenerating gland, in hemiadrenalectomized animals (compensatory adrenal growth) as well as in ACTH-stimulated one (95)(96)(97). Furthermore, NMU had no effect on basal and ACTH-stimulated corticosterone secretion by freshly isolated or cultured inner zone adrenocortical cells, nor did it change their cytosolic Ca ++ concentration (93,94).…”