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Effects of melanocortin-4 receptor agonists and antagonists on expression of genes related to reproduction in spotted scat, Scatophagus argus

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Abstract

Melanocortin-4 receptor (Mc4r) function related to reproduction in fish has not been extensively investigated. Here, we report on gene expression changes by real-time PCR following treatment with Mc4r agonists and antagonists in the spotted scat (Scatophagus argus). Using in vitro incubated hypothalamus, the Mc4r nonselective agonist NDP-MSH ([Nle4, D-Phe7]-α-melanocyte stimulating hormone; 10−6 M) and selective agonist THIQ (N-[(3R)-1, 2, 3, 4-Tetrahydroisoquinolinium-3-ylcarbonyl]- (1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine; 10−7 M) significantly increased the expression of gnrh (Gonadotropin releasing hormone), while the Mc4r nonselective antagonist SHU9119 (Ac-Nle-[Asp-His-DPhe/DNal(2′)-Arg-Trp-Lys]-NH2; 10−6 M) and selective antagonist Ipsen 5i (compound 5i synthesized in Ipsen Research Laboratories; 10−6 M) significantly inhibited gnrh expression after 3 h of incubation. In incubated pituitary tissue, NDP-MSH and THIQ significantly increased the expression of fshb (Follicle-stimulating hormone beta subunit) and lhb (Luteinizing hormone beta subunit), while SHU9119 and Ipsen 5i significantly decreased fshb and lhb expression after 3 h of incubation. During the in vivo experiment, THIQ (1 mg/kg bw) significantly increased gnrh expression in hypothalamic tissue, as well as the fshb and lhb expression in pituitary tissue 12 h after abdominal injection. Furthermore, Ipsen 5i (1 mg/kg bw) significantly inhibited gnrh expression in hypothalamic tissue, as well as fshb and lhb gene expression in pituitary tissue 12 h after abdominal injection. In summary, Mc4r singling appears to stimulate gnrh expression in the hypothalamus, thereby modulating the synthesis of Fsh and Lh in the pituitary. In addition, Mc4r also appears to directly regulate fshb and lhb levels in the pituitary in spotted scat. Our study suggests that Mc4r, through the hypothalamus and pituitary, participates in reproductive regulation in fish.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AGRP:

Agouti-related protein

cAMP:

Cyclic adenosine monophosphate

Fsh:

Follicle-stimulating hormone

GtH:

Gonadotropin hormones

HPG:

Hypothalamic–pituitary–gonadal

HPPS:

Hypothalamo-pituitary portal system

Ipsen 5i:

Compound 5i synthesized in Ipsen Research Laboratories

Lh:

Luteinizing hormone

MCR:

Melanocortin receptor

Mc4r:

Melanocortin-4 receptor

α-MSH:

α-melanocyte-stimulating hormone

NDP-MSH:

[Nle4, D-Phe7]-α-melanocyte-stimulating hormone

POMC:

Proopiomelanocortin

Gnrh:

Gonadotropin-releasing hormone

SHU9119:

(Ac-Nle-[Asp-His-DPhe/DNal(2′)-Arg-Trp-Lys]-NH2)

THIQ:

(N-[(3R)-1,2,3,4-tetrahydroisoquinolinium3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1 H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-2-oxoethylamine)

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Acknowledgements

This study was supported by grants from Zhanjiang Science and Technology Bureau (2016A03017), Natural Science Foundation of Guangdong Province (2016A030313743), Guangdong Ocean University Natural Science Research Program (2015 and 2016), Project of Provincial Key Platform and Major Scientific Research of Colleges and Universities in Guangdong (2015KTSCX058), Sail Projects of Guangdong (2014.1), Marine Fishery Science and Technology Extension Projects of Guangdong (A201408A06 and A201608B01).

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    1. Key Laboratory of Marine Ecology and Aquaculture Environment of Zhanjiang, Key Laboratory of Aquaculture in South China Sea for Aquatic Economic Animal of Guangdong Higher Education Institutes, Fisheries College, Guangdong Ocean University, Zhanjiang, 524088, China

      Dong-Neng Jiang, Jian-Tao Li, Hua-Pu Chen, Si-Ping Deng, Chun-Hua Zhu & Guang-Li Li

    2. Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, 36849, USA

      Ya-Xiong Tao

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    D.-N. Jiang and J.-T. Li contributed equally and should be considered as co-first authors.

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    Jiang, DN., Li, JT., Tao, YX. et al. Effects of melanocortin-4 receptor agonists and antagonists on expression of genes related to reproduction in spotted scat, Scatophagus argus . J Comp Physiol B 187, 603–612 (2017). https://doi.org/10.1007/s00360-017-1062-0

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