Based on theoretical considerations, we have synthesized two tetrapeptides (Thr-Arg-Asp-Leu and Lys-Thr-Cys-Thr) that inhibit binding of 125I-hFSH to receptors in calf testis. These synthetic tetrapeptides and their analogs have potential use as novel contraceptive agents in that they may selectively impair FSH stimulated function of Sertoli cells.
The specific aims of this project are: 1) to optimize the FSH receptor-radioligand binding assay for quantitation of these peptides, 2) to enhance the potency of these peptides through analog synthesis or other chemical modification, 3) to determine the biological activity of such synthetic peptides (i.e., inhibition of the actions of FSH both in vitro and in vivo and 4) to perform fertility testing of the most promising peptides using intact male rats. The methodology of this project relies on the use of in vitro assays for initial screening of peptides with FSH binding inhibition activity. In vitro biological assays will include measurement of the effects of the synthetic peptides on the response of cultured Sertoli cells to FSH stimulation, as for example, estradiol production. In vivo assays will include classical bioassays for FSH such as the hCG augmented ovarian weight gain assay and, later, measurement of sperm production and fertility in rodents. The long term objective of this proposal is to evaluate the pharmacological potential of these synthetic peptides and their derivatives as contraceptive agents.
