TIME-INTEGRATED MEASUREMENT OF HORMONE AVAILABILITY

THE PURPOSE OF THIS RESEARCH IS PRODUCTION AND TESTING OF A NEEDLE-IMPLANTABLE DEVICE FOR ESTIMATING LONG-TERM TISSUE AVAILABILITY OF THE HORMONE CORTICOSTERONE IN RATS. THIS WORK CONTRIBUTES TO THE LONG-TERM GOAL OF DEVELOPING A SIMILAR DEVICE FOR MEASUREMENT OF THE TISSUE AVAILABILITY OFA BROAD RANGE OF COMPOUNDS IN BOTH RESEARCH AND MEDICAL SETTINGS. THE DEVICE OPERATES ON THE DIFFUSION-SINK PRIN- CIPLE: A COMPARTMENT IS CREATED IN WHICH THE CONCENTRATION OF THE COMPOUND OF INTEREST IS MAINTAINED AT A NEGLIGIBLE LEVEL, BY ACTION OF A BINDING PROTEIN WITH HIGH AFFINITY ANDSPECIFICITY FOR THAT COMPOUND. CONSEQUENTLY, THE COMPOUND CONTINUOUSLY DIFFUSES INTO THE DEVICE AT A RATE THAT DEPENDSON ITS AVAILABILITY IN THE IMMEDIATE ENVIRONMENT AND THE DIFFUSIVE RESISTANCE OFFERED BY THE WALLS OF THE DEVICE. BYMEASURING THE ACCUMULATION OF A COMPOUND BY A SUBCUTANEOUSLYIMPLANTED DEVICE OVER A SUITABLE TIME INTERVAL, A DIRECT ESTIMATE OF ITS TISSUE AVAILABILITY IS OBTAINED. COMPACT- NESS AND HIGH CAPACITY ARE GAINED BY USING CONCENTRATED BINDING PROTEINS PURIFIED BY AFFINITY CHROMATOGRAPHY. POTENTIAL APPLICATIONS OF THIS DEVICE INCLUDE MEASUREMENT OFTIME-INTEGRATED CORTISOL AVAILABILITY IN CLINICAL PSYCHIATRYFOR DIFFERENTIAL DIAGNOSIS OF ENDOGENOUS DEPRESSION OR MELANCHOLIA.