The notion that activins and/or inhibins are local mediators of gonadotropin within the ovary is further supported by the finding that gonadotropin increased the expression of activin A- and inhibin A-like molecules. In vivo administration of hCG increased intensities of the 26- and 32-kDa bands in a time-dependent manner In addition, hCG appears to differentially regulate the expression of inhibin A-and activin A-like molecules. The expression of inhibin Alike molecules reached maximal level at 12 h after hCG injection and remained elevated at 24 and 30 h post-injection. However, a significantly higher level of expression of the activin A-like molecule was observed only at 24 h after hCG injection. In mammals, the regulation of activin and inhibin production are also under the control of gonadotropins. FSH and hCG stimulated both activin and inhibin production in a dose-dependent fashion in cultured porcine granulosa cells. Similarly, in human granulosa-luteal cells, FSH and Lh also enhanced the secretion of inhibin A and activin A. However, in rat granulosa cells, FSH or activators of the cAMP signalling pathway stimulated inhibin, but not activin, production.
The site(s) of activin A and inhibin A actions in the zebrafish ovary remains unclear at present. Both inhibin and activin have been reported to modulate steroidogenesis, including progesterone production, in mammals. It is possible that activin A and inhibin A may stimulate MIH production, which in turn, induces oocyte maturation. On the other hand, our finding that FS-288 partially blocked MIH-induced maturation suggests that activin A and/or in-hibin A may act downstream of MIH, possibly at the level of the oocyte. A direct action on oocytes for activin is also supported by the expression of activin type II receptors in zebrafish oocytes.
In summary, this study demonstrates that activin A, in-hibin A-like molecule, and FS are present in the zebrafish ovary. In addition, activin A and inhibin A stimulate final oocyte maturation. Furthermore, FS neutralizes the effect of activin A and inhibin A on oocyte maturation and blocks gonadotropin- and MIH-induced final oocyte maturation. These findings, together with our previous study demonstrating the presence of activin receptor mRNA in the ze-brafish ovary, suggest that activin A and inhibin A are physiological regulators of final oocyte maturation. The sites of activin A and inhibin A actions are currently under investigation.