Elastin-Derived Peptide VGVAPG Affects Production and Secretion of Testosterone in Mouse Astrocyte In Vitro

Astrocytes play many distinct roles in the nervous system providing structural support for neurons and maintaining blood-brain barrier integrity. Steroid hormones exhibit a broad spectrum of actions in the central and peripheral nervous system, acting as trophic factors affecting cell differentiation and synaptic plasticity. In steroidogenesis, astrocytes play a key role by producing cholesterol, progesterone (P₄), testosterone (T), and estradiol (E₂). Currently there are only few studies which show that the Gly-Val-Ala-Pro-Gly (VGVAPG) peptide may affect the metabolism of astrocytes. Therefore, due to the role of neurosteroids, it is necessary to determine whether VGVAPG affects the level of E₂, P₄, and T in astrocytes. Primary mouse astrocytes were maintained in DMEM/F12 without phenol red, and supplemented with 10% charcoal/dextran-treated fetal bovine serum. Cells were exposed to 10 nM and 1 µM VGVAPG peptide and co-treated with cSrc kinase inhibitor I. After cell stimulation, we measured the Ki67 protein level and the production and secretion of P₄, T, and E₂. Our report presents the novel finding that the VGVAPG peptide affects the production and secretion of neurosteroids in astrocytes in vitro. The VGVAPG peptide increases the production of P₄; however, at the same time, it decreases the secretion of P₄ by astrocytes. On the other hand, it stimulates the production and secretion of T. Interestingly, the production of E₂ did not change in any studied time interval. The expression of Ki67 protein increased after 48 h of exposition to the VGVAPG peptide. The cSrc kinase inhibitor I prevented most of the effects of VGVAPG peptide. Therefore, we postulate that T and cSrc kinase may be responsible for increasing astrocyte proliferation.