The goldfish (Carassius auratus) as a model for neuroendocrine signaling

Popesku, Jason T.; Martyniuk, Christopher J.; Mennigen, Jan A.; Xiong, Hua; Zhang, Dapeng; Xia, Xuhua; Cossins, Andrew R.; Trudeau, Vance L.

doi:10.1016/j.mce.2008.06.017

Cited by 149 publications

(115 citation statements)

References 183 publications

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“…Therefore a possible influence of GABA on isotocin may potentially contribute to the observed changes in isotocin, as was also discussed with respect to the fluoxetineinduced decrease on AVP expression in male wrasses (54). However, in a recent meta-analysis using the same microarray platform as in this study, the goldfish hypothalamic transcriptome was compared between different pharmacological treatments (45). The microarray data set for fluoxetine from this study was also compared with a muscimol (GABA A agonist) study in goldfish.…”

Section: Fluoxetine In Female Goldfishmentioning

confidence: 92%

Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)

Mennigen

Martyniuk

Crump

et al. 2008

Physiological Genomics

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128

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. Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus). Physiol Genomics 35: 273-282, 2008. First published September 2, 2008; doi:10.1152/physiolgenomics.90263.2008.-We investigated the effects of fluoxetine, a selective serotonin reuptake inhibitor, on neuroendocrine function and the reproductive axis in female goldfish. Fish were given intraperitoneal injections of fluoxetine twice a week for 14 days, resulting in five injections of 5 g fluoxetine/g body wt. We measured the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in addition to their metabolites with HPLC. Homovanillic acid, a metabolite in the dopaminergic pathway, increased significantly in the hypothalamus. Plasma estradiol levels were measured by radioimmunoassay and were significantly reduced approximately threefold after fluoxetine treatment. We found that fluoxetine also significantly reduced the expression of estrogen receptor (ER)␤1 mRNA by 4-fold in both the hypothalamus and the telencephalon and ER␣ mRNA by 1.7-fold in the telencephalon. Fluoxetine had no effect on the expression of ER␤2 mRNA in the hypothalamus or telencephalon. Microarray analysis identified isotocin, a neuropeptide that stimulates reproductive behavior in fish, as a candidate gene affected by fluoxetine treatment. Real-time RT-PCR verified that isotocin mRNA was downregulated approximately sixfold in the hypothalamus and fivefold in the telencephalon. Intraperitoneal injection of isotocin (1 g/g) increased plasma estradiol, providing a potential link between changes in isotocin gene expression and decreased circulating estrogen in fluoxetine-injected fish. Our results reveal targets of serotonergic modulation in the neuroendocrine brain and indicate that fluoxetine has the potential to affect sex hormones and modulate genes involved in reproductive function and behavior in the brain of female goldfish. We discuss these findings in the context of endocrine disruption because fluoxetine has been detected in the environment. brain; estrogen receptors; isotocin; microarray; Prozac FLUOXETINE (PROZAC), a selective serotonin reuptake inhibitor (SSRI) (46), has been used in several studies in fish to investigate the serotonergic modulation of the endocrine system (55). A racemic mixture of two lipophilic enantiomers, fluoxetine is metabolized by cytochrome P-450 isoenzymes to the active metabolite norfluoxetine (46). In humans, fluoxetine is primarily excreted in urine as ϳ20%-30% unchanged parent compound, while metabolites are largely excreted as pharmacologically active norfluoxetine and inactive fluoxetine glucuronide (62).Fluoxetine also has effects on reproduction in several vertebrates. For example, in the goldfish (Carassius auratus), combined intraperitoneal administration of 10 g/g fluoxetine and 10 g/g serotonin (5-HT) elevated luteinizing hormone (LH) levels relative to 5-HT administration alone 2 h after treatment (55). Japanese medaka (Oryzias latipes) exposed to waterborne 0.1 and 0.5 g/l fluoxetine for 4 wk sh...

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Section: Fluoxetine In Female Goldfishmentioning

confidence: 92%

Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)

Mennigen

Martyniuk

Crump

et al. 2008

Physiological Genomics

Self Cite

128

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“…The description, validation, and use of our goldfish-carp microarrays have been published previously (31,32,35,46,64). Version 1.1 of the cDNA array was used in the present study and contains 8,664 clones printed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Zhang

Popesku

Martyniuk

et al. 2009

Physiological Genomics

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Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17␤-estradiol (E2). Specific inhibition of aromatase activity by fadrozole has been shown to impair estrogen production and influence neuroendocrine and reproductive functions in fish, amphibians, and rodents. However, very few studies have identified the global transcriptomic response to fadrozole-induced decline of estrogens in a physiological context. In our study, sexually mature prespawning female goldfish were exposed to fadrozole (50 g/l) in March and April when goldfish have the highest AroB activity and maximal gonadal size. Fadrozole treatment significantly decreased serum E2 levels (4.7 times lower; P ϭ 0.027) and depressed AroB mRNA expression threefold in both the telencephalon (P ϭ 0.021) and the hypothalamus (P ϭ 0.006). Microarray expression profiling of the telencephalon identified 98 differentially expressed genes after fadrozole treatment (q value Ͻ0.05). Some of these genes have shown previously to be estrogen responsive in either fish or other species, including rat, mouse, and human. Gene ontology analysis together with functional annotations revealed several regulatory themes for physiological estrogen action in fish brain that include the regulation of calcium signaling pathway and autoregulation of estrogen receptor action. Real-time PCR verified microarray data for decreased (activin-␤A) or increased (calmodulin, ornithine decarboxylase 1) mRNA expression. These data have implications for our understanding of estrogen actions in the adult vertebrate brain.aromatase; microarray; fish; brain MAIN ESTROGENS estradiol-17␤ (E2) and estrone (E1) play fundamental regulatory roles in neuroendocrine and reproductive systems. Through binding to its nuclear estrogen receptors (nER)-␣ and nER-␤, E2 regulates transcriptional process of target genes whose promoters contain estrogen-responsive elements (ERE) (57). In addition to this classical nuclear action, E2 also has membrane actions in which a unique membrane receptor is utilized to rapidly activate a series of signaling pathways (52,70). Since the signaling pathway activation will ultimately influence the transcriptional activities of downstream transcription factors including nERs, membrane actions of E2 provide another mode to regulate genomic gene expression (70). Fish are unique models in which to study E2 action because there is high activity of the B-subtype aromatase (AroB; the product of cyp19a1b), the enzyme responsible for synthesizing E2 from testosterone (T), in the neuroendocrine brain, telencephalon (Tel) and hypothalamus (Hyp) (42). Moreover, in contrast to mammals where aromatase and nER are commonly expressed in neurons, current studies in fish and birds strongly suggest that AroB is exclusively expressed in radial glial cells and nER is mostly expressed in neurons (16,43). Thus, the local...

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“…The dopamine antagonist was used to reduce dopaminergic inhibition and to allow maximal s-GnRHa-stimulated LH release (Trudeau, 1997;Popesku et al, 2008). Levels of gtha, fshb, and lhb were taken as indicator for pituitary responsiveness to GnRH.…”

Section: Primary Cell Culture and In Vitro Incubationmentioning

confidence: 99%

“…The decapeptide GnRH stimulates production and release of gonadotropins from the pituitary. Contrary to GnRH, dopamine is the principal inhibitory neurohormone controlling LH release (Popesku et al, 2008;Trudeau, 1997;Trudeau et al, 2000;Yaron, 1995). In the present study, to reduce the inhibitory effects of DA on LH release, we used the combination of s-GnRHa plus domperidone (DOM, antagonist of dopamine type 2 receptors) to maximally stimulate LH release.…”

Section: Reduced Sensitivity Of Gh-transgenic Pituitaries To Stimulatmentioning

confidence: 99%

Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

Cao

Chen

Wei

et al. 2014

General and Comparative Endocrinology

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The goldfish (Carassius auratus) as a model for neuroendocrine signaling

Cited by 149 publications

References 183 publications

Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)

Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

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