Characterization of inhibin alpha subunit (inha) in the zebrafish: evidence for a potential feedback loop between the pituitary and ovary.

Inhibin and activin are closely related disulphide-linked dimers that belong to the transforming growth factor beta superfamily. Although inhibin has been extensively studied in mammals, the information about its existence and function in lower vertebrates is very scarce. Using zebrafish as a model, the present study demonstrated that the inhibin-specific alpha subunit (inha) was predominantly expressed in the gonads and no transcript could be detected in other tissues including the pituitary and brain. In the ovary, the expression of inha was restricted to the somatic follicle cells surrounding the oocyte, together with the beta subunits (inhbaa and inhbb). This was further supported by the absence of its expression in the ovulated unfertilized eggs. During folliculogenesis, inha expression in the follicles slightly but steadily increased from primary growth to the mid-vitellogenic stage; however, its expression surged dramatically at the full-grown stage. Interestingly, the expression level of inha decreased significantly in the follicles whose oocytes were undergoing spontaneous maturation or germinal vesicle breakdown. When tested on cultured ovarian fragments, both goldfish pituitary extract and forskolin significantly stimulated inha expression. Further experiments showed that recombinant zebrafish FSH but not LH significantly increased inha expression in the same assay system. When tested in vitro, human inhibin A exhibited a slight but significant inhibitory effect on 17alpha, 20beta-dihydroxyprogesterone-induced oocyte maturation after 4 h incubation. The stimulation of inha expression by FSH and the potential inhibition of FSH by inhibin suggest a possible existence of a negative feedback loop between the pituitary and ovary in the zebrafish.