Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.

This research investigates how the hormone thyrotropin releasing hormone (TRH) affects the release of specific peptides in horses, both healthy and those with a condition known as Cushing’s disease. The study reveals that TRH directly causes the release of these peptides in both types of horses.

Research Context and Objective

• The focus of the research was to comprehend the response of horses, those in good health and those with a disease known as Pituitary Pars Intermedia Dysfunction (PPID) or Cushing’s disease, to Thyrotropin Releasing Hormone (TRH).
• In humans with Cushing’s disease or Nelson’s syndrome, TRH increases plasma cortisol levels. But the reason behind this reaction is not entirely understood.
• Horses with PPID, unlike humans with the condition, primarily have adenomas (a type of tumor) that originate from the pars intermedia (PI, a part of the pituitary gland) rather than the pars distalis (PD). It was therefore posited that the horses’ TRH response differs from humans.

Investigation and Key Findings

• The researchers hypothesized that TRH directly prompts the PI in both healthy horses and those with PPID to discharge peptides derived from proopiomelanocortin (POMC).
• The research team used alpha-Melanocyte Stimulating Hormone (alpha-MSH) as a marker for a PI response and Adrenocorticotropic Hormone (ACTH) as a marker for a PD response.
• They found a significant rise in plasma concentration of alpha-MSH and a moderate, yet notable increase in ACTH following TRH treatment in healthy horses.
• The study confirmed the ability of TRH to directly stimulate release of POMC peptides through a series of tests using PI and PD tissue explants (tissue pieces taken and cultured in laboratory settings).
• The presence of TRH receptor mRNA (molecules vital in gene expression process) in PI tissue obtained from normal and PPID-affected horses was also confirmed using a process known as the Reverse Transcriptase Polymerase Chain Reaction.

Conclusions Derived from the Research

• The research concluded that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors usually present on melanotropes (cells in the pituitary gland).
• The increase in plasma cortisol levels following administration of TRH in horses with PPID is probably due to the discharge of ACTH from the enlarged PI.