Cathepsin D mediates tachykinin-induced secondary follicle growth independent of the hypothalamic-pituitary-gonadal axis in mice.

Background: Cathepsin D is an aspartic protease responsible for the proteolytic processing of vitellogenin at the early stages of folliculogenesis in oviparous vertebrates. Previously, we identified a multifunctional neuropeptide, tachykinin (TK), as an inducer of cathepsin D that promotes vitellogenic follicle growth in the ascidian Methods: Ovaries of 2-week-old ICR mice were used. Results: Immunohistochemical analysis revealed that cathepsin D is co-localized with TK receptors in granulosa cells of secondary follicles in the ovaries of two-week-old mice, which are sexually immature and in which the hypothalamus-pituitary-gonadal (HPG) axis is not yet functional. TK treatment of the ovaries significantly increased Conclusion: Collectively, these results indicate that cathepsin D plays essential roles in mouse secondary follicle growth. Recently, we also demonstrated that ovarian TKs promote secondary follicle growth in mice, primarily in a paracrine/autocrine manner. Combined with these findings, the present study leads us to propose an evolutionary scenario in which TK-cathepsin D signaling functions as a conserved mechanism for HPG axis-independent follicle growth across chordates, which may be more broadly conserved than the vertebrate-specific, HPG axis-dependent systems.