The current study attempted to evaluate the antagonistic activity of compounds isolated and purified from the marine algae Padina arborescens during cultivation. The compounds were collected on a filter, concentrated on ODS columns and separated by HPLC. Two peaks that showed competitive progesterone binding activity with membrane progesterone receptor α (mPRα) were purified. Their physiological activity was further uncovered by in vitro and in vivo oocyte maturation and ovulation-inducing assays using zebrafish. The compounds inhibited the induction of oocyte maturation and ovulation. Moreover, the results showed that the compounds have antagonistic activity against mPRα. The purified compounds with antagonistic activity against mPRα would be considered as new pharmaceutical candidate.
Oocyte maturation in medaka is induced by the maturation-inducing hormone (MIH) via its membrane receptor. The most likely candidates for the membrane receptor are membrane progestin receptors (mPRs). In order to characterize the mPRα subtype of medaka, a human cell line expressing the mPRα gene of medaka was established and its steroid binding property was assessed. The α subtype exhibited high binding affinity for 17,20β-DHP, the MIH in medaka. Treatment with a morpholino antisense oligonucleotide to mPRα blocked oocyte maturation in vivo. These results suggest that the medaka mPRα protein acts as an intermediary during MIH-induced oocyte maturation in medaka in a manner similar to that described previously for fish species.Fish oocytes are arrested at prophase of the first meiotic division prior to oocyte maturation. Oocyte maturation, or the resumption of meiosis, in fish is triggered by the steroidogenic maturation-inducing hormone, MIH. MIH is produced by follicle cells under the control of leutinizing hormone (LH) released from the pituitary gland (6). A novel cDNA for the membrane receptor for MIH, named as membrane progestin receptor α (mPRα), was cloned from spotted seatrout (Cynoscion nebulosus) (25). We subsequently cloned mPRα and other subtypes of mPRs in the goldfish (Carassius auratus) (16,21). Microinjection of mPRα and mPRβ antisense oligonucleotides blocked the maturation of goldfish oocytes, suggesting that the mPRα and β proteins act as receptors for MIH in goldfish. Based on phylogenetic analysis, mPRs can be categorized into a new protein family of G protein-coupled receptors, the progestin and adipoQ receptors (PAQR) family (13). AdipoQ in humans is an anti-diabetic adipokine, adiponectin. PAQR1 and PAQR2 correspond to adipoQ receptor 1 (AdipoR1) and adipoQ receptor 2 that serve as the major receptors for adiponectin (23). Recently, the three-dimensional structure of crystallized AdipoR1 has been resolved (12). A novel class of proteins with a seven-transmembrane domain structure and a zinc-binding cavity was discovered. PAQR family contains 11 genes and among them three genes, PAQR7, 8 and 5 correspond to subtypes of mPRs, mPRα, β and γ, respectively. Based on the analysis of proteins expressed in human breast cancer cells, PAQR6 and 9 were also categorized as new subtypes of mPR (mPRδ and ε) (8). Thus five subtypes of mPRs are reported at present. These five genes are known to be conserved between vertebrates. The expression of mPR mRNAs has been observed in various tissues in the human (24). The broad distribution of mPRs in different tissues suggests that mPRs perform various functions in a large range of target tissues. Another well-established small fish model medaka usually spawns daily within 1 h of the onset of light for a number of consecutive days under a photoperi-
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