Neuropeptide Y modulates steroid production of human adrenal H295R cells through Y1 receptors

P Kempná1, M Körner, B Waser

  • 1Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University Children's Hospital Bern, Switzerland.

Insights

Neuropeptide Y (NPY) directly impacts human adrenal cortisol production by activating the Y1 receptor. This study found NPY decreases cortisol levels and specific gene expression in adrenal cells, without affecting proliferation.

Area of Science:

  • Endocrinology
  • Neuroendocrinology
  • Molecular Biology

Background:

  • Neuropeptide Y (NPY) is widely distributed in the nervous system.
  • The Y1 receptor subtype is present in the human adrenal cortex and adrenal tumors, but its function remains unclear.

Purpose of the Study:

  • To investigate the function of the Y1 receptor in human adrenal cells.
  • To determine the effects of NPY on steroidogenesis and cell proliferation in the human adrenal cortex.

Main Methods:

  • Utilized radioactive ligand binding assays to confirm Y1 receptor expression in NCI-H295R cells.
  • Stimulated MEK/ERK1/2 pathways to verify functional Y1 receptors.
  • Measured steroidogenesis (11-deoxycortisol, cortisol) and gene expression (HSD3B2, CYP21A2) following NPY treatment.

Main Results:

  • NPY specifically binds to and activates the Y1 receptor in H295R cells, stimulating the MEK/ERK1/2 pathway.
  • NPY and PYY significantly reduced 11-deoxycortisol and cortisol production, an effect reversed by the Y1 antagonist BIBP2336.
  • NPY decreased HSD3B2 and CYP21A2 mRNA expression but did not influence cell proliferation.

Conclusions:

  • Neuropeptide Y directly regulates human adrenal cortisol production via the Y1 receptor.
  • NPY signaling in the adrenal cortex may play a role in modulating steroidogenesis.

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