Synthetic seminal plasma peptide inhibits testosterone production in rat Leydig cells.

Native peptides, extracted from human and bovine seminal plasma, were characterized at the endocrine and paracrine level as modulators of follicle stimulating hormone activity. Similarly to other peptides extracted from chromatin of various tissues, seminal plasma peptides show regulatory activity on RNA synthesis by exerting inhibitory effects on transcription in vitro and in neoplastic and fast-growing cells. Biochemical and mass spectrometry analysis of highly purified fraction from seminal plasma allowed to design and synthesize a peptide with the following amino acid sequence: pGlu-Val-Ala-Asp-Ser-Asp-Gln-Asn (Mancinelli et al. Biol. Chem. 380: 31-40, 1999). Preliminary data on the activity of synthetic peptide have shown an inhibition of testosterone production by frog testes incubated in presence of peptide. The aim of our research was to study the role of synthetic peptide in mammalian testicular steroidogenesis. Continuous, isoosmotic Percoll gradient was utilized to isolate highly purified Leydig cells from rat testicular interstitial cell suspensions. 5 x 104 cells were incubated with increasing doses of synthetic peptide in presence of 50 mU LH for 180 min at 37°C. Testosterone levels in the incubation medium were measured by radioimmunoassay. The results showed the inhibition of testosterone production by Leydig cells with a bell-shape curve. 10-8 M synthetic peptide exerted the highest testosterone inhibition (58%). The basal production of testosterone, without LH stimulation, remained unchanged after treatment of rat Leydig cells with synthetic seminal plasma peptide. Toxicological analysis of synthetic peptide was carried out on carcinoma cell line A431 with negative results. These data suggest a probable role of synthetic seminal plasma peptides in modulating testicular steroidogenesis.