An {\it in vivo\/} evaluation of the LHRH agonist deslorelin for therapeutic application

Lori Ann Hayes Underhill, University of Rhode Island


Luteinizing hormone releasing hormone (LHRH) is a hypothalamic decapeptide which controls release of gonadotropins from the anterior pituitary. Exogenous administration of the peptide for extended periods of time results in chemical castration in males, thus providing an alternative to orchiectomy and estrogen therapy for the treatment of prostate cancer. Several analogs to LHRH have been developed which provide increased potency and longer half lives than the native LHRH molecule. In males, focus for the therapeutic application of these analogs has been on androgen-dependant diseases. Cambridge Scientific in collaboration with the Chemical Engineering Department at Northeastern University have developed a delivery system for (D-$\rm Trp\sp6,Des$-Gly,$\rm NH\sb2\sp{10}\rbrack LHRH$ for potential use as a male contraceptive. Innovative use of an LHRH analog for this therapeutic application requires extensive investigation of the in vivo activity of the peptide and its effect on endogenous androgen levels.^ Preliminary evaluation of this product requires development of an appropriate assay applicable to in vivo systems as well as generation of pharmacokinetic data on the release pattern. In the absence of these developmental components, the safety and efficacy of such products for use in humans cannot be reliably established in conformance with FDA requirements and USP recommendations. This dissertation focuses on the development and validation of an analytical test to evaluate the LHRH agonist, deslorelin, in vivo, which can potentially be used in a compendial test regimen for future USP standardization of the product. ^

Subject Area

Biology, Animal Physiology|Chemistry, Pharmaceutical|Biology, Veterinary Science

Recommended Citation

Lori Ann Hayes Underhill, "An {\it in vivo\/} evaluation of the LHRH agonist deslorelin for therapeutic application" (1997). Dissertations and Master's Theses (Campus Access). Paper AAI9805255.