Secretagogin triggers stress process in the brain

Published 2014-11-27 12:10. Updated 2014-11-27 12:59Denna sida på svenska

Researchers at Karolinska Institutet and MedUni Vienna in Austria have identified a new molecular mechanism to regulate stress. In a study published in the EMBO Journal, they show that the protein secretagogin plays an important role as a trigger in the release of the stress hormone CRH, which only then enables stress processes in the brain to be transmitted to the pituitary gland and onwards to the body.

"If, however, the presence of secretagogin, a calcium-binding protein, is suppressed, then the Corticotropin Releasing Hormone, CRH, might not be released in the hypothalamus of the brain thus preventing the triggering of hormonal responses to stress in the body," says Tibor Harkany, a Professor of Neurobiology at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and affiliated to the MedUni Vienna.

The hypothalamus requires the assistance of CRH to stimulate the production and release of the hormone ACTH from cells in the pituitary gland into the blood stream. Thus, ACTH reaches the adrenal cortex and once there stimulates the production and release of further hormones, including the vital stress hormone cortisol. Upon stress, the hypothalamus responds by releasing CRH and thus produces the critical signal orchestrating also ACTH and cortisol secretion. However, if this cycle is interrupted, it is not possible for acute, and even chronic, stress to arise.

Extended understanding

Secretagogin was discovered 15 years ago by researchers at the MedUni Vienna, in connection with research on the pancreas. The researchers behind the current study now hope that their findings will provide an extended understanding of how hormonal responses to stress are generated.

"This could result in a further development, where secretagogin is deployed as a tool to treat stress, perhaps in people suffering from mental illness such as depression, burn out or posttraumatic stress disorder, but also in cases of chronic stress brought on by pain”, says Tomas Hökfelt, MD, Senior Professor at the Department of Neuroscience, Karolinska Institutet.

The study has been funded by the Swedish Research Council, The Swedish Brain Foundation, Petrus and Augusta Hedlund’s Foundation, Novo Nordisk Foundation, Karolinska Institutet, MedUni Vienna, the French National Research Agency, the European Commission, and the Wellcome Trust.

Publication

A secretagogin locus of the mammalian hypothalamus controls stress hormone release
Roman A Romanov, Alán Alpár, Ming-Dong Zhang, Amit Zeisel, André Calas, Marc Landry, Matthew Fuszard, Sally L Shirran, Robert Schnell, Árpád Dobolyi, Márk Oláh, Lauren Spence, Jan Mulder, Henrik Martens, Miklós Palkovits, Mathias Uhlén, Harald H Sitte, Catherine H Botting, Ludwig Wagner, Sten Linnarsson, Tomas Hökfelt & Tibor Harkany
EMBO Journal, online first 27th November 2014, doi: 10.15252/embj.201488977

NeurobiologyPsychiatric disorders