Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin.

Growth and reproduction are closely related. Growth hormone (GH)-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and incubation. The expression of (glycogen synthase) and (insulin-like growth factor binding protein) as well as blood glucose concentrations are lower in GH-transgenic carp. (agouti-related protein 1) and (somatolactin ), which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as (gonadotropin-releasing hormone receptor 2), (gonadotropin hormone, alpha polypeptide), (follicle stimulating hormone, beta polypeptide), [luteinizing hormone, beta polypeptide] in the pituitary, (aromatase A) in the gonad, and (aromatase B) in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary (gonadotropin inhibitory hormone), (dopamine receptor D1), (dopamine receptor D3), and (dopamine receptor D4) exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary expression, and ovarian germinal vesicle breakdown . In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the pituitary might be part of the response to overexpression of GH and the resulting delay in puberty onset.