Australian Regenerative Medicine Institute

Activin, Inhibin, and Follistatin in Zebrafish Ovary: INTRODUCTION(2)

Biological activities of activins are mediated through specific cell surface receptors, known as serine/threonine kinase receptors. A functional receptor is a complex comprising two different proteins, namely the type I and type II receptors. Complementary DNAs encoding two subtypes of the type II receptor (ActR-IIA and -IIB) and two subtypes of the type I receptor (ActR-IA and -IB) have been cloned from a variety of species. Activin first binds to the type II receptor, and this complex recruits the type I receptor. The type II receptor subsequently phosphorylates the type I receptor, which in turn phosphorylates downstream signals, such as Smads. The structure of the inhibin receptor is unknown, although specific binding sites for inhibin have been characterized in several tissues, such as pituitary, ovary, and testis. Inhibin also shows affinity for type II activin receptors.

Follistatins (FS) are monomeric glycoproteins that bind activins with high affinity and inhibin with lower affinity. Multiple forms of FS have been characterized in mammals. FS-288 and FS-315 are derived from alternative splicing of FS mRNA, whereas FS-300 and FS-303 are proteolytic products of FS-315. In tissues and biological fluids, FS form complexes with activins and inhibins. FS have been shown to neutralize bioactivities of activin by preventing the interaction of activins with their receptors and by increasing the breakdown of activin through enhancement of activin uptake into cells.

Oocyte maturation has been extensively studied in tele-osts. Three major factors are known to be important in this process; gonadotropin, maturation-inducing hormone (MIH; 17a, 20p-dihydroxyprogesterone), and maturation promoting factor (MPF). Gonadotropin stimulates the production of MIH by follicular cells, which in turn acts on the oocyte surface to activate MPF. Recently, we have cloned cDNA encoding ActR-IIB and found that ActR-IIB mRNA is expressed in the oocyte at different stages of development in zebrafish. These results have led us to hypothesize that activins may regulate oocyte development and maturation in fish. To test this hypothesis, we have examined the role of activin A and its related molecules, inhibin A and FS-288, in oocyte maturation. In addition, the presence of these molecules in the zebrafish ovary was also investigated.

Category: Ovary

Tags: Activin, Inhibin, Oocyte, Zebrafish Ovary