In vertebrates, the tachykinin system includes tachykinin genes, which encode one or two peptides... more In vertebrates, the tachykinin system includes tachykinin genes, which encode one or two peptides each, and tachykinin receptors. The complexity of this system is reinforced by the massive conservation of gene duplicates after the whole-genome duplication events that occurred in vertebrates and furthermore in teleosts. Added to this, the expression of the tachykinin system is more widespread than first thought, being found beyond the brain and gut. The discovery of the co-expression of neurokinin B, encoded by the tachykinin 3 gene, and kisspeptin/dynorphin in neurons involved in the generation of GnRH pulse, in mammals, put a spotlight on the tachykinin system in vertebrate reproductive physiology. As food intake and reproduction are linked processes, and considering that hypothalamic hormones classically involved in the control of reproduction are reported to regulate also appetite and energy homeostasis, it is of interest to look at the potential involvement of tachykinins in the...
Corticotropin-releasing hormone (CRH) was discovered for its role as a brain neurohormone control... more Corticotropin-releasing hormone (CRH) was discovered for its role as a brain neurohormone controlling the corticotropic axis in vertebrates. An additional crh gene, crh2, paralog of crh (crh1), and likely resulting from the second round (2R) of vertebrate whole genome duplication (WGD), was identified in a holocephalan chondrichthyan, in basal mammals, various sauropsids and a non-teleost actinopterygian holostean. It was suggested that crh2 has been recurrently lost in some vertebrate groups including teleosts. We further investigated the fate of crh1 and crh2 in vertebrates with a special focus on teleosts. Phylogenetic and synteny analyses showed the presence of duplicated crh1 paralogs, crh1a and crh1b, in most teleosts, resulting from the teleost-specific WGD (3R). Crh1b is conserved in all teleosts studied, while crh1a has been lost independently in some species. Additional crh1 paralogs are present in carps and salmonids, resulting from specific WGD in these lineages. We iden...
We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon,t... more We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon,tshβaandtshβb, issued from teleost-specific whole genome duplication. The transcript expression oftshβb, but not oftshβa, peaks at the time of smoltification, which revealed a specific involvement oftshβbparalog in this metamorphic event.Tshβaandtshβbare expressed by distinct pituitary cells in salmon, likely related to TSH cells from thepars distalisandpars tuberalis, respectively, in mammals and birds. The present study aimed at investigating the neuroendocrine and endocrine factors potentially involved in the differential regulation oftshβaandtshβbparalogs, using primary cultures of Atlantic salmon pituitary cells. The effects of various neurohormones and endocrine factors potentially involved in the control of development, growth, and metabolism were tested. Transcript levels oftshβaandtshβbwere measured by qPCR, as well as those of growth hormone (gh), for comparison and validation. ...
In various vertebrate species, dopamine (DA) exerts an inhibitory action on reproduction. In the ... more 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 ce...
Smoltification is a metamorphic event in salmon life history, which initiates downstream migratio... more Smoltification is a metamorphic event in salmon life history, which initiates downstream migration and pre-adapts juvenile salmon for seawater entry. While a number of reports concern thyroid hormones and smoltification, few and inconclusive studies have addressed the potential role of thyrotropin (TSH). TSH is composed of a α-subunit common to gonadotropins, and a β-subunit conferring hormone specificity. We report the presence and functional divergence of duplicated TSH β-subunit paralogs (tshβa and tshβb) in Atlantic salmon. Phylogeny and synteny analyses allowed us to infer that they originated from teleost-specific whole genome duplication. Expression profiles of both paralogs in the pituitary were measured by qPCR throughout smoltification in Atlantic salmon from the endangered Loire-Allier population raised in a conservation hatchery. This revealed a striking peak of tshβb expression in April, concomitant with downstream migration initiation, while tshβa expression remained r...
The European eel () presents a blockade of sexual maturation at a prepubertal stage due to a defi... more The European eel () presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. We previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of two genes. In the present study, we cloned and sequenced and cDNAs from the eel brain. The tissue distributions of and transcripts, as investigated by quantitative real-time PCR, showed that both genes are primarily expressed in the eel brain and pituitary. The two 10-residue long sequences characteristic of kisspeptin, eel Kp1(10) and Kp2(10), as well as two longer sequences, predicted as mature peptides, eel Kp1(15) and Kp2(12), were synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected Chinese hamster ovary cells, we found that the four synthesized eel peptides were able to induce [Ca] responses, indicating their ability to bind mammalian KissR-1 and to activate sec...
Following the discovery of kisspeptin (Kiss) and its receptor (GPR54 or KissR) in mammals, phylog... more Following the discovery of kisspeptin (Kiss) and its receptor (GPR54 or KissR) in mammals, phylogenetic studies revealed up to three Kiss and four KissR paralogous genes in other vertebrates. The multiplicity of Kiss and KissR types in vertebrates probably originated from the two rounds of whole-genome duplication (1R and 2R) that occurred in early vertebrates. This review examines compelling recent advances on molecular diversity and phylogenetic evolution of vertebrate Kiss and KissR. It also addresses, from an evolutionary point of view, the issues of the structure–activity relationships and interaction of Kiss with KissR and of their signaling pathways. Independent gene losses, during vertebrate evolution, have shaped the repertoire ofKissandKissRin the extant vertebrate species. In particular, there is no conserved combination of a givenKisstype with aKissRtype, across vertebrate evolution. The striking conservation of the biologically active ten-amino-acid C-terminal sequence ...
While gonadotropin‐releasing hormone (GnRH) is considered as the major hypothalamic factor contro... more 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 (N...
The regulation of growth hormone (GH) by thyroid hormones (THs) has been shown to present species... more The regulation of growth hormone (GH) by thyroid hormones (THs) has been shown to present species variation. We investigated the regulation of GH in the eel, a representative of an ancient group of teleosts. In vivo administration of triiodothyronine (T(3)) or thyroxine (T(4)) significantly reduced pituitary and serum GH levels, as measured by homologous RIA. In order to investigate the ability of THs to regulate GH production directly at the pituitary level, we used a long-term, serum-free primary culture of eel pituitary cells. Both T(3) and T(4) inhibited GH release in a concentration-dependent manner, producing up to 50% inhibition at 10 nM, with an ED(50) of <0.2 nM, within the range of their physiological circulating levels. Other hormones also acting via the nuclear receptor superfamily, such as sex steroids (testosterone, estradiol and progesterone) and corticosteroid (cortisol), had no effect on GH release in vitro, underlining the specificity of the regulatory effect of...
Insulin-like growth factor (IGF)-I has been suggested as a potential signal linking growth and pu... more Insulin-like growth factor (IGF)-I has been suggested as a potential signal linking growth and puberty in mammals. Using the juvenile European eel as a model, we employed a long-term, serum-free primary culture of pituitary cells to study the direct effect of IGF-I on gonadotrophin (GtH-II=LH) production. IGF-I increased both cell content and release of GtH-II in a time- and dose-dependent manner. IGF-I and IGF-II had similar potencies but insulin was 100-fold less effective, suggesting the implication of an IGF type 1 receptor. Other growth and metabolic factors, such as basic fibroblast growth factor and thyroid hormones, had no effect on GtH-II production. IGF-I did not significantly increase the number of GtH-II immunoreactive cells, indicating that its stimulatory effect on GtH-II production does not result from gonadotroph proliferation. Comparison of IGF-I and somatostatin (SRIH-14) effects showed that both factors inhibited growth hormone (GH) release but only IGF-I stimulat...
Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteopo... more Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralization. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisol-treated eels. We demonstrated that cortisol induced a significant bone demineralization of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and the degree of mineralization measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of di...
In vertebrates, the tachykinin system includes tachykinin genes, which encode one or two peptides... more In vertebrates, the tachykinin system includes tachykinin genes, which encode one or two peptides each, and tachykinin receptors. The complexity of this system is reinforced by the massive conservation of gene duplicates after the whole-genome duplication events that occurred in vertebrates and furthermore in teleosts. Added to this, the expression of the tachykinin system is more widespread than first thought, being found beyond the brain and gut. The discovery of the co-expression of neurokinin B, encoded by the tachykinin 3 gene, and kisspeptin/dynorphin in neurons involved in the generation of GnRH pulse, in mammals, put a spotlight on the tachykinin system in vertebrate reproductive physiology. As food intake and reproduction are linked processes, and considering that hypothalamic hormones classically involved in the control of reproduction are reported to regulate also appetite and energy homeostasis, it is of interest to look at the potential involvement of tachykinins in the...
Corticotropin-releasing hormone (CRH) was discovered for its role as a brain neurohormone control... more Corticotropin-releasing hormone (CRH) was discovered for its role as a brain neurohormone controlling the corticotropic axis in vertebrates. An additional crh gene, crh2, paralog of crh (crh1), and likely resulting from the second round (2R) of vertebrate whole genome duplication (WGD), was identified in a holocephalan chondrichthyan, in basal mammals, various sauropsids and a non-teleost actinopterygian holostean. It was suggested that crh2 has been recurrently lost in some vertebrate groups including teleosts. We further investigated the fate of crh1 and crh2 in vertebrates with a special focus on teleosts. Phylogenetic and synteny analyses showed the presence of duplicated crh1 paralogs, crh1a and crh1b, in most teleosts, resulting from the teleost-specific WGD (3R). Crh1b is conserved in all teleosts studied, while crh1a has been lost independently in some species. Additional crh1 paralogs are present in carps and salmonids, resulting from specific WGD in these lineages. We iden...
We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon,t... more We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon,tshβaandtshβb, issued from teleost-specific whole genome duplication. The transcript expression oftshβb, but not oftshβa, peaks at the time of smoltification, which revealed a specific involvement oftshβbparalog in this metamorphic event.Tshβaandtshβbare expressed by distinct pituitary cells in salmon, likely related to TSH cells from thepars distalisandpars tuberalis, respectively, in mammals and birds. The present study aimed at investigating the neuroendocrine and endocrine factors potentially involved in the differential regulation oftshβaandtshβbparalogs, using primary cultures of Atlantic salmon pituitary cells. The effects of various neurohormones and endocrine factors potentially involved in the control of development, growth, and metabolism were tested. Transcript levels oftshβaandtshβbwere measured by qPCR, as well as those of growth hormone (gh), for comparison and validation. ...
In various vertebrate species, dopamine (DA) exerts an inhibitory action on reproduction. In the ... more 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 ce...
Smoltification is a metamorphic event in salmon life history, which initiates downstream migratio... more Smoltification is a metamorphic event in salmon life history, which initiates downstream migration and pre-adapts juvenile salmon for seawater entry. While a number of reports concern thyroid hormones and smoltification, few and inconclusive studies have addressed the potential role of thyrotropin (TSH). TSH is composed of a α-subunit common to gonadotropins, and a β-subunit conferring hormone specificity. We report the presence and functional divergence of duplicated TSH β-subunit paralogs (tshβa and tshβb) in Atlantic salmon. Phylogeny and synteny analyses allowed us to infer that they originated from teleost-specific whole genome duplication. Expression profiles of both paralogs in the pituitary were measured by qPCR throughout smoltification in Atlantic salmon from the endangered Loire-Allier population raised in a conservation hatchery. This revealed a striking peak of tshβb expression in April, concomitant with downstream migration initiation, while tshβa expression remained r...
The European eel () presents a blockade of sexual maturation at a prepubertal stage due to a defi... more The European eel () presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. We previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of two genes. In the present study, we cloned and sequenced and cDNAs from the eel brain. The tissue distributions of and transcripts, as investigated by quantitative real-time PCR, showed that both genes are primarily expressed in the eel brain and pituitary. The two 10-residue long sequences characteristic of kisspeptin, eel Kp1(10) and Kp2(10), as well as two longer sequences, predicted as mature peptides, eel Kp1(15) and Kp2(12), were synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected Chinese hamster ovary cells, we found that the four synthesized eel peptides were able to induce [Ca] responses, indicating their ability to bind mammalian KissR-1 and to activate sec...
Following the discovery of kisspeptin (Kiss) and its receptor (GPR54 or KissR) in mammals, phylog... more Following the discovery of kisspeptin (Kiss) and its receptor (GPR54 or KissR) in mammals, phylogenetic studies revealed up to three Kiss and four KissR paralogous genes in other vertebrates. The multiplicity of Kiss and KissR types in vertebrates probably originated from the two rounds of whole-genome duplication (1R and 2R) that occurred in early vertebrates. This review examines compelling recent advances on molecular diversity and phylogenetic evolution of vertebrate Kiss and KissR. It also addresses, from an evolutionary point of view, the issues of the structure–activity relationships and interaction of Kiss with KissR and of their signaling pathways. Independent gene losses, during vertebrate evolution, have shaped the repertoire ofKissandKissRin the extant vertebrate species. In particular, there is no conserved combination of a givenKisstype with aKissRtype, across vertebrate evolution. The striking conservation of the biologically active ten-amino-acid C-terminal sequence ...
While gonadotropin‐releasing hormone (GnRH) is considered as the major hypothalamic factor contro... more 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 (N...
The regulation of growth hormone (GH) by thyroid hormones (THs) has been shown to present species... more The regulation of growth hormone (GH) by thyroid hormones (THs) has been shown to present species variation. We investigated the regulation of GH in the eel, a representative of an ancient group of teleosts. In vivo administration of triiodothyronine (T(3)) or thyroxine (T(4)) significantly reduced pituitary and serum GH levels, as measured by homologous RIA. In order to investigate the ability of THs to regulate GH production directly at the pituitary level, we used a long-term, serum-free primary culture of eel pituitary cells. Both T(3) and T(4) inhibited GH release in a concentration-dependent manner, producing up to 50% inhibition at 10 nM, with an ED(50) of <0.2 nM, within the range of their physiological circulating levels. Other hormones also acting via the nuclear receptor superfamily, such as sex steroids (testosterone, estradiol and progesterone) and corticosteroid (cortisol), had no effect on GH release in vitro, underlining the specificity of the regulatory effect of...
Insulin-like growth factor (IGF)-I has been suggested as a potential signal linking growth and pu... more Insulin-like growth factor (IGF)-I has been suggested as a potential signal linking growth and puberty in mammals. Using the juvenile European eel as a model, we employed a long-term, serum-free primary culture of pituitary cells to study the direct effect of IGF-I on gonadotrophin (GtH-II=LH) production. IGF-I increased both cell content and release of GtH-II in a time- and dose-dependent manner. IGF-I and IGF-II had similar potencies but insulin was 100-fold less effective, suggesting the implication of an IGF type 1 receptor. Other growth and metabolic factors, such as basic fibroblast growth factor and thyroid hormones, had no effect on GtH-II production. IGF-I did not significantly increase the number of GtH-II immunoreactive cells, indicating that its stimulatory effect on GtH-II production does not result from gonadotroph proliferation. Comparison of IGF-I and somatostatin (SRIH-14) effects showed that both factors inhibited growth hormone (GH) release but only IGF-I stimulat...
Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteopo... more Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralization. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisol-treated eels. We demonstrated that cortisol induced a significant bone demineralization of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and the degree of mineralization measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of di...
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Papers by Sylvie Dufour