Attainment and maintenance of sexual maturity depends upon complex endocrine communication between the central nervous system, anterior pituitary gland and gonads. Approximately twenty percent of the married couples in the United States experience some form of infertility. To a large extent, the cause of an infertile state is due to inadequate or inappropriate interaction between the brain and the pituitary gland. The brain secrets a decapeptide, luteinizing hormone releasing hormone (LHRH) which intersects with the pituitary to stimulate the gonadotropins, LH and FSH. The gonadotropins are essential for gametogenesis and steroidogenesis and therefore reproductive competence. Infertility that is the result of inadequate pituitary stimulation by LHRH can be reversed by administration of exogenous LHRH. However, administration of LHRH must be in a pulsatile fashion. Continuous exposure of the pituitary to LHRH places the recipient in a refractory and therefore anovulatory state. Thus, treatment of infertility with LHRH requires that the patient be administered intravenous LHRH in an intermittent fashion through a battery operated influsion pump. While the results of this treatment have been encouraging, the patient's life style is comprised during the replacement period by the infusion pump and indwelling venous cannulae. The proposal detailed herein describes our plan to develop the technology of an implantable delivery system. This completely biodegradable """"""""pump"""""""" will be implanted subcutaneously and deliver LHRH pulse without additional manipulation and need not be removed. This technology could be employed to deliver other peptides besides LHRH that exert a biologic action when delivered to the target tissue in a pulsatile fashion.
