What Causes Pituitary Pars Intermedia Dysfunction?

While several mechanisms for PPID have been proposed, Dianne McFarlane, DVM, PhD, Dipl. ACVIM, assistant professor of physiological sciences at Oklahoma State University's Center for Veterinary Health Sciences, suggested that it is a neurodegenerative disease. This seems to be supported by the fact that her research has found almost no dopaminergic (dopamine-producing) neurons in the pars intermedia of affected horses, while there are quite a few in young horses or unaffected horses of similar age. She presented these ideas at the 2006 AAEP Convention.

The lack of dopamine is critical, as she noted that the activity of the pars intermedia is normally inhibited (controlled) by dopamine. Without dopamine, the pars intermedia produces much more hormone than it should, causing the clinical signs of PPID. Similar activity occurs in other species when dopamine is experimentally inhibited, she reported. This explains why the medication pergolide helps so many horses with PPID--it replaces dopamine activity and thus inhibits pars intermedia hormones. It also explains why another popular treatment--trilostane--doesn't always work as well.

McFarlane explained that trilostane acts on the adrenal gland to control secretion of cortisol hormone--"stress hormone." This helps control biochemical stress, but it doesn't act on the originating problem in the pars intermedia.

"I'm hesitant to recommend trilostane partially because it is only available compounded, and because it doesn't act against the inciting factor," she noted. "Pergolide treats in three ways: It protects neurons, adds dopamine, and has antioxidant activity."

Why would a horse's dopaminergic neurons degenerate? McFarlane speculated that oxidative stress, which is more prevalent in PPID horses, and misfolding of a protein called alpha-synuclein, a nerve terminal protein, might play large roles. Misfolding (improperly developing into a form other than its characteristic functional shape) of this protein can be caused by oxidative stress as well.

An interesting side note is that this pathway of disease is the same as that proposed for Parkinson's disease in humans, and many biochemical features of Parkinson's closely resemble features of PPID in horses.

"Dopaminergic neurons are particularly vulnerable to oxidative damage, because dopamine metabolism itself produces free radicals (chemically active atoms or molecular fragments that are missing electrons and damage large molecules within cells while attempting to achieve a more stable configuration)," she commented.

Other contributing factors might include inflammation and mitochondrial dysfunction (altered activity in the parts of cells that produce energy for carrying out the cell's functions).

PPID Prevention

"I think obesity drives chronic stress, which is a risk factor for neurodegeneration," McFarlane said.

"If we're going to prevent disease, controlling obesity will be very important. Also measure selenium (an antioxidant mineral that horses need in small quantities) and address that if needed, and keep in mind that antioxidant therapy might slow progression of the disease.

"Mitochondrial dysfunction is known to be a contributing factor to Parkinson's disease, and agricultural chemical usage contributes to Parkinson's in humans--these chemicals might well affect horses too," she suggested. "Also, ponies and Morgans seem to be more susceptible to the disease. What that genetic factor is, we'll understand better with more research. Understanding the mechanisms of disease is essential to knowing how to prevent this disease in these animals."

 


 

Get research and health news from the American Association of Equine Practitioners 2006 Convention in The Horse's AAEP 2006 Wrap-Up sponsored by OCD Equine. Files are available as free PDF downloads.

About the Author

Christy M. West

Christy West has a BS in Equine Science from the University of Kentucky, and an MS in Agricultural Journalism from the University of Wisconsin-Madison.

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