In humans, as in the other mammals, the neuroendocrine control of reproduction is ensured by the brain-pituitary gonadotropic axis. Multiple internal and environmental cues are integrated via brain neuronal networks, ultimately leading to the modulation of the activity of gonadotropin-releasing hormone (GnRH) neurons. The decapeptide GnRH is released into the hypothalamic-hypophysial portal blood system and stimulates the production of pituitary glycoprotein hormones, the two gonadotropins luteinizing hormone and follicle-stimulating hormone. A novel actor, the neuropeptide kisspeptin, acting upstream of GnRH, has attracted increasing attention in recent years. Other neuropeptides, such as gonadotropin-inhibiting hormone/RF-amide related peptide, and other members of the RF-amide peptide superfamily, as well as various nonpeptidic neuromediators such as dopamine and serotonin also provide a large panel of stimulatory or inhibitory regulators. This paper addresses the origin and evolution of the vertebrate gonadotropic axis. Brain-pituitary neuroendocrine axes are typical of vertebrates, the pituitary gland, mediator and amplifier of brain control on peripheral organs, being a vertebrate innovation. The paper reviews, from molecular and functional perspectives, the evolution across vertebrate radiation of some key actors of the vertebrate neuroendocrine control of reproduction and traces back their origin along the vertebrate lineage and in other metazoa before the emergence of vertebrates. A focus is given on how gene duplications, resulting from either local events or from whole genome duplication events, and followed by paralogous gene loss or conservation, might have shaped the evolutionary scenarios of current families of key actors of the gonadotropic axis.

In various vertebrate species, dopamine (DA) exerts an inhibitory action on reproduction. In the European eel, DA plays a pivotal role in the inhibitory control of gonadotroph function and the blockade of puberty. In vivo studies have suggested that this effect is mediated by receptors pharmacologically related to the D2 family. In the European eel, two distinct D2 receptor (D2‐R) paralogous genes have been identified (D2A‐R and D2B‐R) and both were shown to be expressed in the pituitary. We investigated the potential role of each paralogue in the control of gonadotroph function in this species. Eel recombinant D2A‐R or D2B‐R were expressed in HEK 293 cells, with a universal Gα subunit, and receptor activation was followed by inositol phosphate production. Recombinant D2‐Rs exhibited a comparable affinity for DA, although they had differential affinities for mammalian D2‐R agonists and antagonists, supporting subtle structure/activity differences. Furthermore, using eel pituitary cell primary cultures, the expression by gonadotroph cells of both native eel D2‐R paralogues was examined by in situ hybridisation of D2A‐R or D2B‐R transcripts, coupled with immunofluorescence of luteinising hormone (LH)β or follicle‐stimulating (FSH)β. LH and to a lesser extent, FSH cells expressed both D2‐R transcripts but with a clear predominance of D2B‐R. Notably, D2B‐R transcripts were detected for the majority of LH cells. Accordingly, using these cultures, we showed that DA potently inhibited basal and testosterone‐stimulated LHβ expression and less potently basal and activin‐stimulated FSHβ expression. We also tested some D2‐R antagonists, aiming to select the most adequate one to be used in innovative protocols for induction of eel sexual maturation. We identified eticlopride as the most potent inhibitor of DA action on basal and stimulated LH expression in vitro. Our data suggest a differential functionalisation of the duplicated receptor genes and demonstrate that mainly D2B‐R is involved in the dopaminergic inhibitory control of eel gonadotroph function.

Dopamine neurotransmission regulates various brain functions, and its regulatory roles are mediated by two families of G protein-coupled receptors: the D1 and D2 receptor families. In mammals, the D1 family comprises two receptor subtypes (D1 and D5), while the D2 family comprises three receptor subtypes (D2, D3 and D4). Phylogenetic analyses of dopamine receptor genes strongly suggest that the common ancestor of Osteichthyes (bony jawed vertebrates) possessed four subtypes in the D1 family and five subtypes in the D2 family. Mammals have secondarily lost almost half of the ancestral dopamine receptor genes, whereas nonmammalian species kept many of them. Although the mammalian situation is an exception among Osteichthyes, the current classification and characterization of dopamine receptors are based on mammalian features, which have led to confusion in the identification of dopamine receptor subtypes in nonmammalian species. Here we begin by reviewing the history of the discovery of dopamine receptors in vertebrates. The recent genome sequencing of coelacanth, gar and elephant shark led to the proposal of a refined scenario of evolution of dopamine receptor genes. We also discuss a current problem of nomenclature of dopamine receptors. Following the official nomenclature of mammalian dopamine receptors from D1 to D5, we propose to name newly identified receptor subtypes from D6 to D9 in order to facilitate the use of an identical name for orthologous genes among different species. To promote a nomenclature change which allows distinguishing the two dopamine receptor families, a nomenclature consortium is needed. This comparative perspective is crucial to correctly interpret data obtained in animal studies on dopamine-related brain disorders, and more fundamentally, to understand the characteristics of dopamine neurotransmission in vertebrates.

Regionalization is a critical, highly conserved step in the development of the vertebrate brain. Discrepancies exist in how regionalization of the anterior vertebrate forebrain is conceived since the `` preoptic area'' is proposed to be a part of the telencephalon in tetrapods but not in teleost fish. To gain insight into this complex morphogenesis, formation of the anterior forebrain was analyzed in 3D over time in zebrafish embryos, combining visualization of proliferation and differentiation markers, with that of developmental genes. We found that the region containing the preoptic area behaves as a coherent morphogenetic entity, organized around the optic recess and located between telencephalon and hypothalamus. This optic recess region (ORR) makes clear borders with its neighbor areas and expresses a specific set of genes (dlx2a, sim1a and otpb). We thus propose that the anterior forebrain (secondary prosencephalon) in teleosts contains three morphogenetic entities (telencephalon, ORR and hypothalamus), instead of two (telencephalon and hypothalamus). The ORR in teleosts could correspond to "telencephalic stalk area'' and `` alar hypothalamus'' in tetrapods, resolving current inconsistencies in the comparison of basal forebrain among vertebrates.

Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

In many teleosts, the stimulatory control of gonadotrope axis by GnRH is opposed by an inhibitory control by dopamine (DA). The functional importance of this inhibitory pathway differs widely from one teleostean species to another. The zebrafish (Danio rerio) is a teleost fish that has become increasingly popular as an experimental vertebrate model. However, the role of DA in the neuroendocrine control of its reproduction has never been studied. Here the authors evaluated in sexually regressed female zebrafish the effects of in vivo treatments with a DA D2 receptor (D2-R) antagonist domperidone, or a GnRH agonist, alone and in combination, on the pituitary level of FSHβ and LHβ transcripts, the gonadosomatic index, and the ovarian histology. Only the double treatment with GnRH agonist and domperidone could induce an increase in the expression of LHβ, in the gonadosomatic index, and a stimulation of ovarian vitellogenesis, indicating that removal of dopaminergic inhibition is required for the stimulatory action of GnRH and reactivation of ovarian function to occur. Using double immunofluorescent staining on pituitary, the authors showed in this species the innervation of LH cells by tyrosine-hydroxylase immunoreactive fibers. Finally, using in situ hybridization and immunofluorescence, the authors showed that the three subtypes of zebrafish DA D2-R (D2a, D2b, and D2c) were expressed in LH-producing cells, suggesting that they all may be involved in mediating this inhibition. These results show for the first time that, in zebrafish, DA has a direct and potent inhibitory action capable of opposing the stimulatory effect of GnRH in the neuroendocrine control of reproduction.

While gonadotropin-releasing hormone (GnRH) is considered as the major hypothalamic factor controlling pituitary gonadotrophins in mammals and most other vertebrates, its stimulatory actions may be opposed by the potent inhibitory actions of dopamine (DA) in teleosts. This dual neuroendocrine control of reproduction by GnRH and DA has been demonstrated in various, but not all, adult teleosts, where DA participates in an inhibitory role in the neuroendocrine regulation of the last steps of gametogenesis (final oocyte maturation and ovulation in females and spermiation in males). This has major implications for inducing spawning in aquaculture. In addition, DA may also play an inhibitory role during the early steps of gametogenesis in some teleost species, and thus interact with GnRH in the control of puberty. Various neuroanatomical investigations have shown that DA neurones responsible for the inhibitory control of reproduction originate in a specific nucleus of the preoptic area (NPOav) and project directly to the region of the pituitary where gonadotrophic cells are located. Pharmacological studies showed that the inhibitory effects of DA on pituitary gonadotrophin production are mediated by DA-D2 type receptors. DA-D2 receptors have now been sequenced in several teleosts, and the coexistence of several DA-D2 subtypes has been demonstrated in a few species. Hypophysiotropic DA activity varies with development and reproductive cycle and probably is controlled by environmental cues as well as endogenous signals. Sex steroids have been shown to regulate dopaminergic systems in several teleost species, affecting both DA synthesis and DA-D2 receptor expression. This demonstrates that sex steroid feedbacks target DA hypophysiotropic system, as well as the other components of the brain-pituitary gonadotrophic axis, GnRH and gonadotrophins. Recent studies have revealed that melatonin modulates the activity of DA systems in some teleosts, making the melatonin-DA pathway a prominent relay between environmental cues and control of reproduction. The recruitment of DA neurons for the neuroendocrine control of reproduction provides an additional brain pathway for the integration of various internal and environmental cues. The plasticity of the DA neuroendocrine role observed in teleosts may have contributed to their large diversity of reproductive cycles.

The silvering process includes various physiological and morphological changes that prepare the future genitors (silver eels) for the oceanic reproductive migration (e.g. Lokman et al. 1998). Silvering also marks the beginning of puberty (Aroua et al. 2005, and Chapter 11). However, silver eels are still sexually immature when they leave the continental habitats, and they remain blocked at this prepubertal stage if prevented from their reproductive migration. Because no maturing or spawning eels have ever been observed in the wild, the silver prepubertal stage is the last known stage of the eel biological cycle (for review, see Dufour et al. 2003). Accordingly, the regulatory mechanisms of puberty, sexual development, migration, and finally spawning are still not well understood. Puberty can be defined as the transformation from a sexually immature juvenile into a mature adult by providing the brain-pituitary-gonad (BPG) axis with its full hormonal and gametogenetic capacity (Norris 1997; Schulz et al. 2000). Puberty is marked by the onset of gametogenesis, and the age of puberty and sexual maturation is determined by genetic factors as well as controlled by the nutritional status and/or body growth rate. Both in teleosts and mammals it seems that activation of the brain neuroendocrine system(s) is the key event to initiate puberty. What leads to this activation is, however, not understood.

In fish like in mammals, dopamine (DA) is a major catecholaminergic neurotransmitter that contributes to many functions of the nervous system like sensory perception, tuning of sensori-motor cues, and hypothalamic and pituitary functions. In the eel, DA inhibits gonadal development, and juvenile silver eels remain blocked at a prepubertal stage if their reproductive migration does not occur. From data in other teleosts and vertebrates, it is suggested that DA would be involved also in the last steps of eel reproduction (oocyte maturation, ovulation, and spermiation) as well as in eel reproductive migration (locomotion and olfaction). Investigating dopaminergic systems in the eel may help in understanding the mechanisms of its complex life cycle and provide new data for its conservation and reproduction. In this article we review the biosynthesis and catabolism of catecholamines and discuss available methods to investigate brain dopaminergic systems in vertebrates and their application to the eel. Immunocytochemistry, in situ hybridization, and different tracing methods are used to map dopaminergic neurons and projections in the brain and pituitary and infer their potential functions. Moreover, variations in dopaminergic activity may be approached by means of quantitative methods like quantitative real-time RT-PCR and HPLC. These tools are currently used to study dopaminergic systems in the eel brain, their anatomy, regulation, and potential roles with special emphasis on the regulation of reproduction and reproductive migration.

Two full-length cDNA encoding putative dopamine D2-like receptors were cloned from the brain of female European eel. The deduced protein sequences, termed D2A- and D2B-R, exhibit closer phylogenetic relationships to vertebrate D2 receptors compared with D3 and D4 or D1 receptors. The two protein sequences share 100% identity within the transmembrane domains containing the highly conserved amino acids involved in dopamine binding. Accordingly, an apparent single population of sites on eel brain membranes bound [H-3]spiperone, a D2-R-specific antagonist, with a K-d of 0.2 +/- 0.04 nM. However, D2A- and D2B-R significantly differ within the amino terminus and the third intracellular loop. As analyzed by quantitative PCR and in situ hybridization, both receptor transcripts were found, with different relative abundance, in the majority of brain areas and in the pituitary, whereas in the retina, olfactory epithelium, spinal cord, and adipose tissue, only D2A- R gene was expressed. Because sex steroid hormones recently have been shown to regulate eel brain dopamine systems, we analyzed the effect of steroids on the amount of D2-R transcripts by quantitative PCR and in situ hybridization. In eels treated with testosterone, the gene expression of the D2B-R, but not D2A- R, was increased in a region-dependent manner. The effect of testosterone on D2B-R transcript levels was mimicked by dihydrotestosterone, a nonaromatizable androgen, whereas estradiol had nostimulatory action, evidencing an androgen receptor-dependent mechanism. Although functionality of the two receptors awaits determination of D2-R proteins, we hypothesize that differences in the tissue expression pattern and hormonal regulation of eel D2A- and D2B-R gene expression could represent selective forces that have contributed to the conservation of the duplicated D2-R. (Endocrinology 150: 1377-1392, 2009)

European silver eels are thought to undergo sexual maturation during their oceanic reproductive migration from the European continent to their spawning area in the Sargasso Sea. Tracking data and various anatomical and physiological features suggest that silver eels migrate in deep sea, leading us to hypothesise that high hydrostatic pressure (HP) influences the induction of eel reproduction. We subjected female and male silver eels to 101ATA for 3 and 7 weeks, respectively, in a hyperbaric chamber equipped with a freshwater recirculation system. In comparison with control eels kept at 1 ATA, HP effects were tested against the messenger RNA levels of pituitary gonadotropins (LHbeta, FSHbeta) using quantitative real-time RT-PCR. The effects of HP on gonadal activity were estimated by measuring gonadosomatic index, oocyte diameter and plasma levels of vitellogenin (Vtg) and sex steroids (E(2), 11-KT). At the pituitary level, LHbeta expression tended to increase while FSHbeta expression decreased in both sex, leading to an increase in the LHbeta/FSHbeta ratio. This suggests a differential effect of HP on the expression of the two gonadotropins. In females submitted to HP, we observed a significant increase in oocyte diameter and plasma levels of 11-KT and E(2). A similar trend was observed for 11-KT plasma levels in males. In females, Vtg plasma levels also significantly increased, reflecting the stimulatory effect of sex steroids on hepatic vitellogenesis. Our results suggest that HP plays a specific and positive role in eel reproduction but additional environmental and internal factors are necessary to ensure complete sexual maturation.

Dopamine (DA), a neurotransmitter present in all vertebrates, is involved in processes such as motor function, learning and behavior, sensory activities, and neuroendocrine control of pituitary hormone release. In the female eel, we analyzed how gonadal steroids regulate brain expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of DA. TH mRNA levels were assayed by quantitative real-time RT-PCR. TH-positive nuclei were also localized by in situ hybridization (ISH) and immunohistochemistry, and the location of TH nuclei that project to the pituitary was determined using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindicarbocyanine perchlorate retrograde tracing. Chronic in vivo treatment with testosterone increasedTHmRNAspecifically in the periglomerular area of the olfactory bulbs and in the nucleus preopticus anteroventralis (NPOav). NPOav was labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindicarbocyanine perchlorate, showing that this nucleus is hypophysiotropic in the eel. The nonaromatizable 5 alpha-dihydrotestosterone gave identical results in both areas, whereas 17 beta-estradiol had no stimulatory effect, showing that the observed stimulatory effects of testosterone were androgen dependent. In teleosts, DA-neurons originating from the NPOav directly inhibit gonadotropic function, and our results indicate an androgen-dependent, positive feedback on this neuroendocrine control in the eel. In mammals, DA interneurons in the olfactory bulbs are involved in the enhancement of olfactory sensitivity and discrimination. Our results in the European eel suggest an androgen-dependent stimulation of olfactory processing, a sensory function believed to be important in eel navigation during its reproductive migration toward the oceanic spawning grounds. To our knowledge, this is the first evidence from any vertebrate of an androgen-dependent effect on DAergic activity in the olfactory bulbs, providing a new basis for understanding the regulation by gonadal steroids of central DAergic systems in vertebrates.

Abstract: In many teleosts, dopamine (DA) exerts direct inhibitory control on gonadotropes, counteracting the stimulatory effect of gonadotropin‐releasing hormone (GnRH) on gonadotropin release. This dual control by GnRH and DA has been demonstrated in various adult teleosts and has major implications for aquaculture. Because of its unique life cycle, the European eel has provided a powerful model for demonstrating the key role of DA in the control of puberty. Data from tetrapods suggest that the inhibitory role of DA on reproduction is not restricted to the teleosts. Thus, DA inhibitory control could represent an ancient evolutionary component in the neuroendocrine regulation of reproduction that may have been differentially maintained throughout vertebrate evolution. The intensity of DA inhibition, its main site of action, and its involvement in the control of puberty, seasonal reproduction, ovulation, spermiation, or even sex change may differ among classes of vertebrates, as well as within smaller phylogenetic units such as teleosts or mammals. An inhibitory role for DA has been reported also in some invertebrates, indicating that neuronal DA pathways may have been recruited in various groups of metazoa to participate in the control of reproduction. In addition to the incontestable GnRH neurons, the recruitment of DA neurons for the neuroendocrine control of reproduction provides an additional brain pathway for the integration of various species‐specific, internal, and environmental cues. In teleosts, the plasticity of the DA neuroendocrine role may have contributed to their large diversity of biological cycles and to their successful adaptation to various environments.

Dopamine (DA) plays a key inhibitory role in pubertal development of the European eel, but how DAergic neuronal activity is regulated is not known in this species. In order to investigate the regulation of DA inhibition at the molecular level, we developed a quantitative real-time RT-PCR (qrtRT-PCR) assay, using the Light Cycler system, for the expression of eel tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. Two different reference genes were compared: the previously cloned eel cytochrome b, and eel acidic ribosomal phosphoprotein P0, the latter of which we cloned and partly sequenced. To further validate the assay, different methods of total RNA extraction were tested and compared. When applied to cDNA extracted from dissected brains of juvenile eels, the expression of TH was highest in the olfactory bulb, followed by the telencephalon including preoptic area, and the di-/mesencephalic areas excluding the optic lobes. TH expression in the optic lobes and in the medulla oblongata was low, whereas no expression could be detected in corpus cerebellum. This distribution pattern is in agreement with earlier studies on TH in the eel using immunohistochemistry, RT-PCR, and Northern blotting. The developed qrtRT-PCR assay provides a new tool for understanding the mechanisms regulating central DA inhibition of puberty in juvenile eels.

Abstract: In the eel, dopamine inhibits pubertal development. To investigate the regulatory mechanisms involved, we developed a quantitative real‐time RT‐PCR assay for measurement of brain expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme in the biosynthesis of dopamine. TH expression was highest in the olfactory bulb, followed by the di‐/mesencephalic areas and the telencephalon/preoptic area. TH expression in the optic lobes and hindbrain was low or below the detection limit. In vivo treatment with testosterone, but not estradiol, resulted in increased TH expression in the forebrain, except the optic tectum, but not in the hindbrain. The results were confirmed by in situ hybridization.

Chez les Mammiferes, le controle neurohormonal des cellules gonadotropes hypophysaires est assure par la gonadoliberine, GnRH. De nombreux travaux menes chez les Poissons Teleosteens montrent que ce controle unique de type stimulateur n’est pas une regle generale chez les Vertebres. La premiere mise en evidence de l’implication d’un facteur neurohormonal inhibiteur, le « GRIF » (gonadotropin-release inhibiting factor), a ete apportee par Peter et al., 1978 par des experiences de lesion cerebrale, chez le poisson rouge, induisant une decharge ovulatoire de LH. Plus tard, il a ete demontre par des experiences in vivo et in vitro que le GRIF n’etait autre que la dopamine, et des etudes neuroanatomiques ont confirme que les neurones dopaminergiques de l’aire preoptique anterieure, projetant jusque dans l’hypophyse, correspondaient bien a ceux qui exercaient une activite GRIF. Le role inhibiteur de la dopamine dans le controle de la LH et de l’ovulation ou de la spermiation a ete etendu a de nombreux Teleosteens adultes, avec des applications en aquaculture ; toutefois, il n’est pas retrouve chez toutes les especes. A des etapes plus precoces de la gametogenese et en particulier dans le controle de la puberte, le role de la dopamine a ete suggere ou refute selon les especes. L’Anguille, grâce a son cycle biologique original, a fourni un modele favorable a la demonstration d’un role cle de la dopamine dans le controle de la puberte. La revue de travaux menes chez les Tetrapodes suggere que l’activite GRIF de la dopamine ne serait pas restreinte aux Teleosteens, qu’elle pourrait avoir une origine evolutive ancienne et aurait ete mise en oeuvre de facon differentielle au cours de l’evolution des Vertebres.

In various adult teleost fishes, LH ovulatory peak is under a dual neurohormonal control that is stimulatory by GnRH and inhibitory by dopamine (DA). We investigated whether DA could also be involved in the inhibitory control of LH at earlier steps of gametogenesis by studying the model of the European eel, Anguilla anguilla, which remains at a prepubertal stage until the oceanic reproductive migration. According to a protocol previously developed in the striped bass, eels received sustained treatments with GnRH agonist (GnRHa), DA-receptor antagonist (pimozide), and testosterone (T) either alone or in combination. Only the triple treatment with T, GnRHa, and pimozide could trigger dramatic increases in LH synthesis and release as well as in plasma vitellogenin levels and a stimulation of ovarian vitellogenesis. Thus, in the prepubertal eel, removal of DA inhibition is required for triggering GnRH-stimulated LH synthesis and release as well as ovarian development. To locate the anatomical support for DA inhibition, the distribution of tyrosine hydroxylase (TH) in the brain and pituitary was studied by immunocytochemistry. Numerous TH-immunoreactive cell bodies were observed in the preoptic anteroventral nucleus, with a dense tract of immunoreactive fibers reaching the pituitary proximal pars distalis, where the gonadotrophs are located. This pathway corresponds to that mediating the inhibition of LH and ovulation in adult teleosts. To our knowledge, this is the first demonstration of a pivotal role for DA in the control of LH and puberty in a juvenile teleost. These data support the view that DA inhibition on LH secretion is an ancient evolutionary component in the neuroendocrine regulation of reproduction that may have been partially maintained throughout vertebrate evolution.

In mammals, the neurohormonal control of the pituitary gonadotropes is provided by the gonadoliberin GnRH. Several studies on teleost fish indicate that a single positive control by GnRH is not a general rule among vertebrates. Peter and colleagues presented the first evidence of an inhibitory neurohormonal factor, "GRIF" (gonadotropin-release inhibiting factor). They induced a preovulatory LH surge by injuring particular brain areas in the goldfish. Subsequent in vivo and in vitro studies identified dopamine as GRIF, and neuroanatomical investigations have demonstrated that dopaminergic neurones in the anterior preoptic area projecting to the pituitary represent the anatomical substrate for GRIF activity. An inhibitory role of dopamine on the control of LH and ovulation/spermiation has been evidenced in many adult teleosts, including its implications for aquaculture. However, dopamine does not play an inhibitory role in all adult teleosts. As regards the early stages of gametogenesis and especially the control of puberty, a role for dopamine has been suggested or rejected depending on species. The European eel has a unique life cycle with a long prepubertal stage, which has made it a useful model to demonstrate the key-role of dopamine in the control of puberty. Data from tetrapods suggest that the role of dopamine as a GRIF is not restricted to the teleosts, but that it may have an ancient evolutionary origin, and has been differentially conserved throughout vertebrate evolution.