Wednesday, February 11, 2026

Pituitary Pars Intermedia Dysfunction (PPID) and the potential role of β-endorphin in diagnosis

Pituitary Pars Intermedia Dysfunction (PPID), commonly known as equine Cushing’s disease, is a common endocrine disorder affecting older horses. The condition is associated with abnormal activity of specialised cells called melanotropes, which are located in the pars intermedia region of the pituitary gland. These cells normally produce several hormones derived from a precursor molecule known as pro-opiomelanocortin (POMC). In horses affected by PPID, melanotropes become overactive, leading to excessive production of several hormones that contribute to the clinical signs observed in the disease.

One of the most important hormones produced by melanotropes is adrenocorticotrophic hormone (ACTH). This hormone stimulates cortisol release from the adrenal glands and is widely used as a diagnostic marker for PPID. Elevated ACTH concentrations in blood samples often support a diagnosis of the disease. However, ACTH may not provide a complete understanding of PPID, as melanotropes also produce other biologically active substances that may influence disease development and clinical signs.

These additional substances include alpha-melanocyte stimulating hormone (α-MSH), corticotropin-like intermediate peptide (CLIP), and β-endorphin. β-endorphin is a peptide hormone composed of 31 amino acids and functions as part of the body’s natural pain and stress regulation system. The amino acid sequence of equine β-endorphin is very similar to that found in humans, differing by only three amino acids. Because β-endorphin is also derived from POMC and secreted by melanotropes, researchers have suggested it may play an important role in the development and progression of PPID.

Traditionally, β-endorphin concentrations in horses have been measured using radioimmunoassay (RIA). However, this technique involves the use of radioactive materials, which presents safety risks and has become less widely available in recent years. In human medicine, enzyme-linked immunosorbent assays (ELISAs) are commonly used as a safer and more accessible alternative for hormone measurement. Researchers have therefore investigated whether commercially available human β-endorphin ELISA tests could be used reliably for equine samples.

A study conducted by Nathalie Fouché and colleagues at the University of Bern, Switzerland, aimed to validate a human β-endorphin ELISA kit for use in horses and to compare β-endorphin concentrations between horses diagnosed with PPID and healthy control horses. Validation of the test involved comparing standard curves generated using both synthetic equine β-endorphin and human β-endorphin. The results demonstrated full parallelism between the curves, indicating the test could accurately measure equine hormone levels.

The researchers also assessed the reliability of the assay by calculating intra-assay and inter-assay variation. These tests measure consistency within a single test plate and between multiple plates. The assay showed acceptable levels of variation, suggesting it is suitable for research use. Additionally, β-endorphin concentrations remained stable in plasma samples over a 24-hour period regardless of centrifugation timing, storage temperature, or storage duration, which supports the practicality of sample handling.

The pilot study compared five horses diagnosed with PPID to twenty healthy aged control horses. The findings revealed significantly higher β-endorphin concentrations in horses with PPID, with median concentrations of 506 pg/mL compared to 35 pg/mL in healthy horses. These results suggest that β-endorphin may be elevated in horses with PPID and could potentially provide additional diagnostic or pathophysiological information alongside ACTH testing.

Overall, this research highlights the possible importance of β-endorphin in understanding PPID and suggests that ELISA-based testing may provide a safer and more accessible method for future investigation. Further studies with larger sample sizes are required to confirm the diagnostic value of β-endorphin in horses with PPID.

For more details, see: 

N. Fouché, J. Howard, V. Gerber, P. Billmann, M. Farinha do Sul, G. Christen, R. Bruckmaier, C. Philipona, N. Besuchet Schmutz, J. Gross,

Pilot study of β-endorphin concentrations in horses with pituitary pars intermedia dysfunction using a newly validated enzyme-linked immunosorbent assay,

Domestic Animal Endocrinology (2026) vol 95,106982

https://doi.org/10.1016/j.domaniend.2025.106982

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