Gonadins, a novel family of glutamyl-tripeptide amides present in the testis with activity in the hypophyseal-gonadal axis

Here we present a new family of endogenous peptides identified in rat testis with structure of glutamyl-tripeptide amides which are also present in plasma. These peptides have different activities in the hypophyseal-gonadal axis. Evidences showing the endocrine activities of some of the peptides are presented. In this communication we demonstrate the presence of peptides with a common structure Glu-X-Pro amide, where X can be one of the following amino acids: glutamic acid, glutamine, aspartic acid, asparragine, phenylalanine or tyrosine. These peptides have been identified by a series of chromatographies and by mass spectrometry. Some of the peptides where tested for its biological activity observing that subcutaneous administration of the peptides Glu-Glu-Pro amide, Glu-Gln-Pro amide and Glu-Phe-Pro amide were able to reduce plasma levels of testosterone and luteinizing hormone (LH) without modification of the levels of follicle stimulating hormone (FSH). The peptide Glu-Asp-Pro amide, however, produced an increase in the levels of testosterone without modifying LH or FSH levels. It is proposed that the glutamyl-tripeptide amides that reduce the levels of testosterone and LH are released from the testis and act in the pituitary via circulation in an endocrine manner. The specific inhibition of LH release is similar to that produced by inhibin on FSH release. On the other hand the peptide that increases the levels of testosterone is produced in the testis and seems to act directly in the testis in a paracrine or autocrine manner. It is proposed here a new mechanism of regulation of hypophyseal-gonadal axis, a negative feedback exerted by the glutamyl-tripeptide amides in the pituitary. Also it is proposed the generic name of gonadins for the novel family of glutamyl-tripeptide amides. We suggest that gonadins could be used in the future as drugs for treatment of different endocrine disorders, hormone-dependent cancer and as contraceptives.