MINIMALLY STRESSFUL MEASUREMENT OF HORMONE AVAILABILITY

RECENT RESEARCH POINTS OUT THE POTENTIAL IMPORTANCE OF HORMONAL FACTORS IN THE DEVELOPMENT OF COGNITIVE AND AFFECTIVE DISORDERS OF AGING. BECAUSE ANIMAL MODELS OF THE COGNITIVE DISORDERS OF AGING EXIST, IT IS DESIRABLE TO STUDY HORMONAL CONTRIBUTIONS TO THE DEVELOPMENT OF THESE DEFICITS IN ANIMALS. WITH TRADITIONAL METHODS, IT IS EXTREMELY DIFFICULT TO MAKE MEANINGFUL MEASUREMENTS OF THE ENDURING ENDOCRINE STATUS OF AN INDIVIDUAL ANIMAL SUBJECT. THESE DIFFICULTIES ARISE BECAUSE THE HORMONES TO BE MEASURED ARE EXTREMELY REACTIVE TO STRESS, ARE NORMALLY SECRETED IN AN EPISODIC OR PULSATILE WAY, AND ARE PREDOMINANTLY PRESENT IN THE CIRCULATION IN PROTEIN-BOUND FORMS THAT ARE NOT DIRECTLY AVAILABLE TO TISSUE. THIS RESEARCH AIMS TO DEVELOP A SIMPLE, CONVENIENT, AND RELIABLE METHOD FOR MAKING CONTINUOUS AND REPEATED MEASUREMENTS OVER SEVERAL DAYS OF THE TISSUE AVAILABILITY OF CORTICOSTEROID HORMONES IN ANIMAL SUBJECTS. THE METHOD USES AN INJECTABLE, CHRONICALLY IMPLANTED DEVICE TO CONTINUOUSLY ACCUMULATE THE HORMONE OF INTEREST AT A RATE PROPORTIONAL TO ITS INTERSTITIAL FLUID CONCENTRATION. ACCUMULATION OF THE HORMONE OVER A DISCRETE TIME INTERVAL, THEREFORE, REFLECTS THE TIME INTEGRAL OF ITS TISSUE AVAILABILITY. BECAUSE CONTACT WITH THE ANIMAL SUBJECT IS GENTLE AND ONLY NECESSARY AT THE BEGINNING AND END OF A MEASUREMENT INTERVAL, STRESS ARTIFACTS ARE MINIMIZED.