PHARMACOLOGY OF THE SEROTONERGIC INHIBITION OF STEROID-INDUCED REINITIATION OF OOCYTE MEIOSIS IN THE TELEOST FUNDULUS-HETEROCLITUS

Serotonin (5-HT) was found to inhibit steroid (17 alpha,20 beta-dihydr oxy-4-pregnen-3-one; 17,20 beta P)-induced resumption of oocyte meiosi s (oocyte maturation) in vitro in the teleost Fundulus heteroclitus. S erotonin inhibited both follicle-enclosed and denuded oocytes, which i ndicates the presence of oocyte-associated 5-HT sensitive sites. The r esponse of oocytes to 5-HT was characterized pharmacologically, i.e., the capacity of serotonergic agonists and antagonists to mimic or bloc k the 5-HT inhibition of the steroid-induced oocyte maturation was ass essed by the changes in the percentage of oocyte germinal vesicle brea kdown (GVBD). Dose-response curves for each compound were drawn and co mpared, The rank order of potency among the agonists was: 5-HT > 5-met hoxytryplamine > tryptamine = 5,6-diHT = 5-carboxidotryptamine > 5,7-d iHT = 5-methoxy-dimethyltryptamine > alpha-methyl-5-HT > 2-methyl-5-HT . Incubation of ovarian follicles with high doses of some antagonists (mianserin and metergoline) induced oocyte GVBD, although this effect was associated with high levels of oocyte atresia during GVBD or short ly after maturation. Consequently, doses of the antagonist too low to induce GVBD were tested for their ability to block the 5-HT inhibitory action; the rank order of potency was: MDL-72222 = metoclopramide > m etergoline > propanolol > ketanserin. Dopamine, acetylcholine, epineph rine, and norepinephrine could also inhibit 17,20 beta P-induced GVBD, although at doses much higher than those of 5-HT; melatonin and hista mine had no effect on oocyte maturation. These results suggest that sp ecific receptors mediate the inhibitory action of 5-HT on the steroic- triggered meiosis resumption. The pharmacological profile of these 5-H T receptors is different from those of any known mammalian 5-HT recept or, although they showed some similarities to the 5-HT1A, 5-HT2, and 5 -HT3 receptors, as well as to 5-HT receptors on oocytes of some bivalv e molluscs. (C) 1997 Wiley-Liss, Inc.