Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
CLINICAL SCIENCES
Non Technical Summary
Equine pituitary pars intermedia dysfunction (PPID), a malfunction of the pituitary gland, is the most common endocrine disease of aged horses and ponies. This debiliating disease, associated with development of life-threatening complications, affects 15-25% of all aged horses, more frequently ponies and Morgan horses. Early recognition and therapeutic intervention is critical to prevent horses with PPID from developing highly debilitating complications. Diagnosis of PPID is complicated by seasonal fluctuation in the expression of the pars intermedia (PI) hormones in the healthy horse. Characterization of the PI seasonal response in healthy and PPID horses is absolutely essential for accurate interpretation of all diagnostic tests of PPID. It is our goal to characterize the month-to-month fluctuation in pars intermedia hormone expression in healthy horses and to determine the role that latitude of residence, breed and PPID has on this physiological process. We hypothesize that hormone release from the healthy equine pituitary pars intermedia is regulated by seasonal change in day length.
Animal Health Component
25%
Research Effort Categories
Basic
75%
Applied
25%
Developmental
(N/A)
Goals / Objectives
Equine pituitary pars intermedia dysfunction (PPID) is the most common endocrine disease of aged horses and ponies. It is associated with development of life-threatening complications including laminitis, secondary infections and insulin resistance. The clinical signs of PPID include hirsutism, which is considered to be essentially pathognomic for PPID. However, development of hirsutism occurs relatively late in course of the disease, this suggests hirsutism alone is not a useful diagnostic indicator if early intervention is the goal. Therefore, specific endocrine diagnostic testing is advised in aged horses with clinically signs compatible with PPID. Currently, the available diagnostic strategies for equine PPID include dynamic tests assessing the pituitary-adrenal axis or measurement of the endogenous plasma concentration of pituitary hormones: adrenocorticotropic hormone (ACTH) or alpha-melanocyte stimulating hormone (alpha-MSH). Interpretation of all PPID diagnostic tests is complicated by the existance of seasonal variation in the expression of the pars intermedia (PI) hormones in the healthy horse. In the fall, PI hormone plasma concentration is increased. As a result, false positive diagnostic tests are common in the fall. Two possible triggers for seasonal events are shortening of day length or change in ambient temperature, in which case it might be expected to start with the onset of cooler weather. Characterization of the PI seasonal response in healthy and PPID horses is essential. Our goal is to characterize the month-to-month fluctuation in pars intermedia hormone expression in healthy horses and to determine the role that latitude of residence, breed and PPID has on this physiological process. We hypothesize that hormone release from the healthy equine pituitary pars intermedia is regulated by seasonal change in day length. Therefore, we expect: a) the seasonal change in plasma concentrations of PI hormones to be evident starting in July, as the day length begins to shorten; b) that horses residing in latitudes further from the equator, where the seasonal change in day length is more extreme, to have a more pronounced seasonal hormone variation compared to those residing closer to the equator. c) that ponies and Morgan horses (thrifty horses) will have a greater change while animals with PPID will show a blunted seasonal change in PI hormones concentrations. Specific Aims: 1) To determine the month-to-month variation in plasma alpha-MSH and ACTH concentration in healthy light horses. 2) To determine if there is a correlation between geographic latitude of residence and magnitude of seasonal variation of plasma alpha-MSH and ACTH concentration in light horses. 3) To compare the magnitude of seasonal variation of plasma alpha-MSH and ACTH concentration in light horses to that of ponies and Morgan horses residing at the same geographic latitude. 4) To determine if seasonal variation of plasma alpha-MSH and ACTH concentration is abolished or blunted in horses with PPID.
Project Methods
Hematology and serum chemistry analysis: CBC and serum chemistry panel will be performed at the regional laboratory for the participating institute. Horses with abnormal findings will be excluded from the study. Horses in the PPID group will not have routine blood analysis performed for inclusion into the study. Endocrine assays: Plasma alpha-MSH concentration will be determined using a radioimmunoassay validated for use in the horse. ACTH will be determined using a radioimmunoassay following validation of the assay for use with equine plasma. Specific Aims 1 and 2: Aplha-MSH is only produced in the PI and therefore is a much more sensitive indication of PI activity. However, plasma alpha-MSH concentration is not a routine commercial test of PPID. ACTH is produced in both the pars distalis and the PI. It is a commonly used diagnostic test by veterinary practitioners. Monitoring seasonal variation in both hormones will provide complementary and independently useful data. Adult (10-16 yrs) healthy light horses will be recruited from an equine population of Helsinki, Finland (latitude 60 degrees north, n=12), Boston, MA (latitude 42 degrees north, n=12) and Gainesville, Florida (latitude 29 degrees north, n=12). Health status will be assessed by history, physical examination, complete blood count (CBC), plasma alpha-MSH and serum chemistry panel. Horses with abnormal findings will be excluded. Horses with a plasma alpha-MSH concentration of 50 pmol/L or higher in a non-fall season or those pregnant or lactating will also be excluded. All ponies will be excluded. Blood will be collected on the 15th day of the month, between 06:00- 12:00 hours. Plasma will be transported on ice, separated by centrifugation within 3 hours of collection and stored at -80 degrees Celsius until shipped for assay. Samples will be packaged frozen on dry ice for shipping to the lab for endocrine assays. Specific Aim 3: To compare the seasonal pattern of plasma alpha-MSH and ACTH concentration in light horses to that in ponies and Morgan horses residing at the same geographic latitude. Healthy ponies (n=12) will be selected from an equine population of Helsinki, Finland. Healthy Morgan horses (n=12) will be selected from the equine referral population of Tufts Cummings School of Veterinary Medicine (TCSVM). Selection criteria will be as described for Aims 1 and 2. Samples will be collected, processed and stored monthly as described for Aims 1 and 2. Horses for the thrifty study groups were not selected from Florida, as we anticipate the seasonal PI response may be blunted or absent in horses at this lower latitude. Specific Aim 4: To determine if seasonal variation in plasma alpha-MSH and ACTH concentration is abolished or blunted in horses with PPID. Horses with PPID (n=12) will be selected from the equine referral population of TCSVM based on the presence of 2 or more clinical signs of PPID. PPID will be confirmed by a plasma alpha-MSH concentration higher than 50 pmol/L in a non-fall season. Horses having received specific therapy for PPID within 3 months will be excluded. Samples will be collected, processed and stored monthly as described for Aims 1 and 2.