17α,20β-Dihydroxy-4-pregnen-3-one, a maturation-inducing hormone in fish oocytes: Mechanisms of synthesis and action

Abstract

Meiotic maturation of fish oocytes is induced by the action of maturation-inducing hormone (MIH). 17α,20β-Dihydroxy-4-pregnen-3-one (17α,20β-DP) was identified as the MIH of several fish species, including salmonid fishes. The interaction of two ovarian follicle cell layers, the thecal and granulosa cell layers, is required for the synthesis of 17α,20β-DP; the thecal layer produces 17α-hydroxyprogesterone that is converted to 17α,20β-DP in granulosa cells by the action of 20β-hydroxysteroid dehydrogenase (20β-HSD). The preovulatory surge of LH-like gonadotropin (GTH II) is responsible for rapid expression of 20β-HSD mRNA transcripts in granulosa cells. 17α,20β-DP acts via a receptor on the plasma membrane of oocytes. A specific 17α,20β-DP receptor has been identified and characterized from defolliculated oocytes of several fish species. The concentrations of 17α,20β-DP membrane receptor increase immediately prior to oocyte maturation. The pertussis toxin-sensitive inhibitory G protein is involved in the signal transduction pathway of 17α,20β-DP. The early steps following 17α,20β-DP action involve the formation of the major mediator of this steroid, maturation-promoting factor, which consists of cdc2 kinase (34 kDa) and cyclin B (46–48 kDa). Immature oocytes contain only monomeric 35 kDa cdc2 and do not stockpile cyclin B, although immature oocytes contain mRNA for cyclin B. 17α,20β-DP induces oocytes to synthesize cyclin B, which in turn activates preexisting 35 kDa cdc2 through its threonine 161 phosphorylation by a threonine kinase (MO15), producing the 34-kDa active cdc2. 17α,20β-DP-induced oocyte maturation is blocked by cordycepin, a polyadenylation inhibitor. Furthermore, cyclin B mRNA was polyadenylated during 17α,20β-DP-induced oocyte maturation. These findings suggest that 17α,20β-DP initiates translation of cyclin B mRNA through cytoplasmic 3′ poly(A) elongation.