5-HT causes an increase in cAMP that stimulates, rather than inhibits, oocyte maturation in marine nemertean worms

In the nemertean worms Cerebratulus lacteus and Micrura alaskensis, 5-HT (= 5-hydroxytryptamine, or serotonin) causes prophase-arrested oocytes to matu re and complete germinal vesicle breakdown (GVBD). To identify the intracel lular pathway that mediates 5-HT stimulation, follicle-free oocytes of neme rteans were assessed for GVBD rates in the presence or absence of 5-HT afte r being treated with various modulators of cAMP, a well known transducer of 5-HT signaling and an important regulator of hormone-induced maturation in general. Unlike in many animals where high levels of intra-oocytic cAMP bl ock maturation, treatment of follicle-free nemertean oocytes with agents th at elevate cAMP (8-bromo-cAMP, forskolin or inhibitors of phosphodiesterase s) triggered GVBD in the absence of added 5-HT. Similarly, 5-HT caused a su bstantial cAMP increase prior to GVBD in nemertean oocytes that had been pr e-injected with a cAMP fluorosensor. Such a rise in cAMP seemed to involve G-protein-mediated signaling and protein kinase A (PKA) stimulation, based on the inhibition of 5-HT-induced GVBD by specific antagonists of these tra nsduction steps. Although the downstream targets of activated PKA remain un known, neither the synthesis of new proteins nor the activation of MAPKs (m itogen-activated protein kinases) appeared to be required for GVBD after 5- HT stimulation. Alternatively, preincubation in roscovitine, an inhibitor o f maturation-promoting factor (MPF), prevented GVBD, indicating that maturi ng oocytes eventually need to elevate their MPF levels, as has been documen ted for other animals. Collectively, this study demonstrates for the first time that 5-HT can cause immature oocytes to undergo an increase in cAMP th at stimulates, rather than inhibits, meiotic maturation. The possible relat ionship between such a form of oocyte maturation and that observed in other animals is discussed.