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Updated: Jun 20, 2026

Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
Published on: March 12, 2019
Neuropeptide Y modulates steroid production of human adrenal H295R cells through Y1 receptors
1Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University Children's Hospital Bern, Switzerland.
Abstract:
Neuropeptide Y (NPY) is abundantly expressed in the nervous system and acts on target cells through NPY receptors. The human adrenal cortex and adrenal tumors express NPY receptor subtype Y1, but its function is unknown. We studied Y1-mediated signaling, steroidogenesis and cell proliferation in human adrenal NCI-H295R cells. Radioactive ligand binding studies showed that H295R cells express Y1 receptor specifically. NPY treatment of H295R cells stimulated the MEK/ERK1/2 pathway, confirming that H295R cells express functional Y1 receptors. Studies of the effect of NPY and related peptide PYY on adrenal steroidogenesis revealed a decrease in 11-deoxycortisol production. RIA measurements of cortisol from cell culture medium confirmed this finding. Co-treatment with the Y1 antagonist BIBP2336 reversed the inhibitory effect of NPY on cortisol production proving specificity of this effect. At mRNA level, NPY decreased HSD3B2 and CYP21A2 expression. However NPY revealed no effect on cell proliferation. Our data show that NPY can directly regulate human adrenal cortisol production.
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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