Neuropeptide-Y family of peptides in the autocrine-paracrine regulation of adrenocortical function.

Neuropeptide-Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are a family of 36-amino-acid peptides, which are widely distributed in the body and act through several subtypes of G-protein-coupled Y receptors. The three members of the NPY-family peptides are contained in the adrenal gland, where they exert various autocrine/paracrine regulatory functions. Binding sites for NPY are present in adrenal medulla and zona glomerulosa (ZG), where also several NPY-ergic fibers end. Binding sites for PYY and PP are prevalently located in the inner adrenocortical zones and adrenal medulla. NPY and PYY inhibit aldosterone secretion of dispersed ZG cells, but this effect has probably to be considered nonspecific and toxic in nature. On the contrary, there are indications that NPY may indirectly stimulate ZG cells, by eliciting the release of catecholamines, which in turn enhance aldosterone secretion. Evidence is also available that NPY modulates the secretory response of ZG cells to their main agonists. PP is able to raise glucocorticoid secretion acting directly on the inner adrenocortical cells. The physiological relevance of these effects of NPY-family peptides remains to be addressed by future experimental studies employing more selective Y receptor agonists and antagonists. In contrast, indirect evidence is available that endogenous NPY-family peptides might play an important role in the modulation of adrenocortical secretory action under paraphysiological or pathological conditions such as like aging, hypoglycemic stress and pheochromocytomas.