Neuropeptide Y modulates the sensitivity of the rat adrenal cortex to stimulation by ACTH

Abstract

Neuropeptide Y (NPY) has been identified in nerves supplying the adrenal cortex of several mammalian species, although its function in this tissue is unknown. The present studies, employing adrenocortical cells prepared by collagenase digestion, have shown that NPY, in the absence of other stimulants, has no effect on steroid secretion by the rat adrenal over a range of peptide concentrations (10(-11) to 10(-6) mol/l). However, in the presence of physiological concentrations of ACTH, which are submaximal for the stimulation of aldosterone secretion, NPY (10(-6) mol/l) significantly enhanced the secretion rate of aldosterone by rat zona glomerulosa cells in response to ACTH. This effect was specific to the rat zona glomerulosa as NPY had no effect on the response to ACTH in rat zona fasciculata cells. The effect of NPY appears to be biphasic, however, as NPY significantly attenuated the steroidogenic response to supramaximal ACTH concentrations: in rat zona glomerulosa cells the aldosterone response to 10(-8) mol ACTH/l was significantly inhibited by NPY. The effect of NPY on the ACTH response appeared to be mediated by changes in the cAMP response. NPY had no effect on the steroidogenic response to potassium ions (K+), but enhanced the response to angiotensin II. NPY (10(-6) mol/l) significantly stimulated inositol 1,4,5-trisphosphate (InsP3) production although this concentration of peptide had no effect on steroid secretion. The effects of NPY on InsP3 production were additive with those of angiotensin II. These results suggest that the role of NPY in the adrenal cortex may be to regulate the sensitivity of the zona glomerulosa to peptide stimulation.

Interactions between the neuropeptide Y system and the hypothalamic-pituitary-adrenal axis

“…These changes are reflected by the concentrations of cAMP. Although NPY does not affect cAMP concentrations in the adrenal cortex, it modifies ACTH-induced increases in cAMP, namely it increases ACTH-dependent cAMP concentrations at low concentrations of ACTH, and decreases cAMP concentrations at high concentrations of ACTH (28). However, the significance of the stimulatory effect of NPY on the synthesis and release of aldosterone is not very important.…”

“…In addition, results from studies of dogs and rats are inconsistent. It has been shown that only intact NPY can stimulate ACTH and cortisol release in dogs, whereas its C-terminal fragment, NPY (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and the NPY analog, NPY (1-36)-OH, are ineffective (12). In contrast, Small et al (18), using different NPY analogs, have obtained results suggesting that the rat hypothalamic NPY receptor, which increased plasma ACTH concentrations, has a fragment activation profile unlike those of Y1-Y4 and Y6 receptors, and appears distinct from the NPY receptor controlling food intake.…”

“…At low ACTH concentrations (comparable to those in plasma) NPY stimulates the steroidogenic response in ZG, which is reflected by increased aldosterone secretion. At high ACTH concentrations, NPY inhibits the stimulatory effect of ACTH on the release of aldosterone (28). These changes are reflected by the concentrations of cAMP.…”

“…Some authors believe that NPY does not influence the release of corticosterone, because it did not affect corticosterone secretion in intact and ACTH-stimulated cells of the zonae fasciculata/reticularis (28). Moreover, prolonged administration of NPY to rats with damaged HPA axis and RAS did not stimulate the growth of the EUROPEAN JOURNAL OF ENDOCRINOLOGY (1999) 140 zona fasciculata and did not alter the plasma corticosterone concentrations (27).…”

Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

“…It is secreted from adrenal chromaffin cells on nerve stimulation (2). As a neuroendocrine hormone in adrenals, NPY can inhibit catecholamine release from chromaffin cells (3), and modulate the sensitivity of zona glomerulosa cells to adrenocorticotropin stimulation (4).…”