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The first report of a gonadotropic substance in an invertebrate hot-water extract of radial nerve cords from starfish Asterias forbesi that induced the shedding of gametes when injected into the coelomic cavity in a ripe individual occurred in 1959. The active substance was named gamete-shedding substance (GSS) or radial nerve factor. GSS is the primary mediator of oocyte maturation and ovulation in starfish. However, the effect of GSS is indirect. Resumption of meiosis in immature oocytes and release from the ovary are induced by a second mediator, maturation-inducing hormone, identified as 1-methyladenine (1-MeAde) in starfish. The role of GSS is to induce 1-MeAde production by ovarian follicle cells. Thus, GSS was redesignated as gonad-stimulating substance (also GSS). Although GSS has been characterized biochemically as a peptide hormone, identification of the chemical structure had to wait until 2009. Fifty years after the initial finding, GSS was purified from the radial nerve cords of starfish Patiria pectinifera (P. pectinifera). The purified hormone was a heterodimer composed of A- and B-chains, with disulfide cross-linkages. Based on its cysteine motif, GSS is classified as a member of the insulin/insulin-like growth factor (IGF)/relaxin superfamily. More specifically, phylogenetic sequence analysis revealed that P. pectinifera GSS is a member of the relaxin-type peptide family. Therefore, GSS in starfish has been redesignated as relaxin-like gonad-stimulating peptide (RGP). Subsequently, orthologs of P. pectinifera RGP have been identified in other starfish species, including Asterias amurensis (A. amurensis), and Aphelasterias japonica (A. japonica).
Figure 1. Structure of radial nerve cords of starfish P. pectinifera and chemical structures of relaxin-like gonad-stimulating peptides (RGP) in various species of starfish. (A) Aboral surface of P. pectinifera. (B) Magnified image of the area in the square in (A). Arrow indicates radial nerve cords. (C) Cross-section of the tissue around radial nerve cord of P. pectinifera. The specimen was stained with hematoxylin-eosin. (D) Alignment of RGP pre-prohormone sequences of P. pectinifera, Acanthaster planci (A. planci), Certonardoa semiregularis (C. semiregularis), P. miniata, Asterisa amurensis (A. amurensis), and A. japonica. The signal peptide, C-peptide, B- and A-chains are indicated. To illustrate the conserved features, the amino acid types are color coded according to their nature with basic residues in blue (Arg, Lys, and His), acidic residues in red (Glu and Asp), hydrophobic residues in green (Ala, Val, Ile, Phe, Trp, Tyr, Pro, and Met), hydrophilic in black (Ser, Thr, Asn, and Gln) and glycine in light blue. The cysteine residues are highlighted in yellow, and the disulfide bonds are shown by solid dark red lines. The abbreviations and the sequence sources [DDBJ accession numbers]: AamRGP, A. amurensis RGP (LC040882); AjaRGP, A. japonica RGP (LC104980); AplRGP-a, A. planci RGP-a (LC033566); AplRGP-b, A. planci RGP-b (19); BM, basement membrane; CL, cuticle layer; CseRGP, C. semiregularis RGP (LC066682); CT, connective tissue; DFC, deep fiber system; EC, epithelical cells; SC, sensory cells; PmiRGP, P. miniata RGP (LC057656); PpeRGP, P. (Asterina) pectinifera RGP (AB496611); RHS, radial heamal sinus; RNC, radial nerve cord; SFS, superficial fiber system; and TF, tube foot.
Figure 2. Overview of RGP. (A) Annual changes in RGP content in radial nerve cords and gonadal index in starfish P. pectinifera. Starfish P. pectinifera were collected monthly from Yokosuka (Kanagawa Prefecture, Japan). More than ten individuals (arm length 30–50 mm) per group were used for measurement of gonadal index () and the preparation of radial nerve cord extracts for the measurement of RGP content (). RGP contents were determined by ELISA (40). The gonadal index was calculated as the gonad weight per body weight × 100. Symbols and bars represent the mean of six independent samples and standard error of the mean (SEM), respectively. Arrow shows timing of spawning. (B)
De novo synthesis, secretion, and hormonal action of RGP. AC, adenylyl cyclase; GPCR, G-protein-coupled receptor; Gs, G-protein as adenylyl cyclase stimulator; Met, methionine; and RXFP, relaxin-family peptide receptor.
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