@article{won_douros_hurt_borski_2016, title={Leptin stimulates hepatic growth hormone receptor and insulin-like growth factor gene expression in a teleost fish, the hybrid striped bass}, volume={229}, ISSN={["1095-6840"]}, DOI={10.1016/j.ygcen.2016.02.003}, abstractNote={Leptin is an anorexigenic peptide hormone that circulates as an indicator of adiposity in mammals, and functions to maintain energy homeostasis by balancing feeding and energy expenditure. In fish, leptin tends to be predominantly expressed in the liver, another important energy storing tissue, rather than in fat depots as it is in mammals. The liver also produces the majority of circulating insulin-like growth factors (IGFs), which comprise the mitogenic component of the growth hormone (GH)-IGF endocrine growth axis. Based on similar regulatory patterns of leptin and IGFs that we have documented in previous studies on hybrid striped bass (HSB: Morone saxatilis×Morone chrysops), and considering the co-localization of these peptides in the liver, we hypothesized that leptin might regulate the endocrine growth axis in a manner that helps coordinate somatic growth with energy availability. Using a HSB hepatocyte culture system to simulate autocrine or paracrine exposure that might occur within the liver, this study examines the potential for leptin to modulate metabolism and growth through regulation of IGF gene expression directly, or indirectly through the regulation of GH receptors (GHR), which mediate GH-induced IGF expression. First, we verified that GH (50nM) has a classical stimulatory effect on IGF-1 and additionally show it stimulates IGF-2 transcription in hepatocytes. Leptin (5 and/or 50nM) directly stimulated in vitro GHR2 gene expression within 8h of exposure, and both GHR1 and GHR2 as well as IGF-1 and IGF-2 gene expression after 24h. Cells were then co-incubated with submaximal concentrations of leptin and GH (25nM each) to test if they had a synergistic effect on IGF gene expression, possibly through increased GH sensitivity following GHR upregulation by leptin. In combination, however, the treatments only had an additive effect on stimulating IGF-1 mRNA despite their capacity to increase GHR mRNA abundance. This suggests that leptin's stimulatory effect on GHRs may be limited to enhancing transcription or mRNA stability rather than inducing full translation of functional receptors, at least within a 24-h time frame. Finally, leptin was injected IP (100ng/g and 1μg/gBW) to test the in vivo regulation of hepatic IGF-1 and GHR1 gene expression. The 100ng/g BW leptin dose significantly upregulated in vivo IGF-1 mRNA levels relative to controls after 24h of fasting, but neither dosage was effective at regulating GHR1 gene expression. These studies suggest that stimulation of growth axis component transcripts by leptin may be an important mechanism for coordinating somatic growth with nutritional state in these and perhaps other fish or vertebrates, and represent the first evidence of leptin regulating GHRs in vertebrates.}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Won, Eugene T. and Douros, Jonathan D. and Hurt, David A. and Borski, Russell J.}, year={2016}, month={Apr}, pages={84–91} }
 @article{won_baltzegar_picha_borski_2012, title={Cloning and characterization of leptin in a Perciform fish, the striped bass (Morone saxatilis): Control of feeding and regulation by nutritional state}, volume={178}, ISSN={["1095-6840"]}, DOI={10.1016/j.ygcen.2012.04.019}, abstractNote={In mammals, leptin is an anorexigenic peptide hormone that regulates energy homeostasis. It is produced predominantly by white adipose tissue and circulates as an endocrine indicator of energy reserves. Teleost leptin has been characterized in a few fish species, but its regulation is not well understood, particularly in response to nutritional status. In this study, we cloned a putative leptin in striped bass (Morone saxatilis) and report the first characterization of leptin in a Perciforme, the largest and most diverse order of fish. The striped bass leptin coding sequence was 65% homologous with pufferfish, 52% with Atlantic salmon, and 46% with human. PCR showed that leptin mRNA was exclusively expressed in the liver, and not adipose or other tissues. The leptin coding sequence of striped bass and the more widely cultured hybrid striped bass variety (HSB; Morone chrysops, white bass × M. saxatilis) were identical. We then evaluated whether the metabolic status of HSB might alter leptin gene expression. Juvenile HSB were subjected to 3 weeks feed deprivation followed by 3 weeks of refeeding. Quantitative PCR showed that fasting for 3 weeks reduced hepatic leptin mRNA levels relative to fed controls. Leptin mRNA levels then increased upon refeeding, albeit levels were not completely restored to those seen in control fish fed throughout the experiment. Intraperitoneal injection of human leptin suppressed appetite in HSB. In as much as hepatic HSB leptin mRNA is regulated by nutritional state and has a corresponding anorexigenic effect, our results suggest that leptin may play a role in energy homeostasis in these advanced Perciformes.}, number={1}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Won, Eugene T. and Baltzegar, David A. and Picha, Matthew E. and Borski, Russell J.}, year={2012}, month={Aug}, pages={98–107} }
 @article{duffy_picha_won_borski_mcelroy_conover_2010, title={Ontogenesis of Gonadal Aromatase Gene Expression in Atlantic Silverside (Menidia menidia) Populations With Genetic and Temperature-Dependent Sex Determination}, volume={313A}, ISSN={["2471-5646"]}, DOI={10.1002/jez.612}, abstractNote={Abstract}, number={7}, journal={JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY}, author={Duffy, Tara A. and Picha, Matthew E. and Won, Eugene T. and Borski, Russell J. and McElroy, Anne E. and Conover, David O.}, year={2010}, month={Aug}, pages={421–431} }
 @article{picha_strom_riley_walker_won_johnstone_borski_2009, title={Plasma ghrelin and growth hormone regulation in response to metabolic state in hybrid striped bass: Effects of feeding, ghrelin and insulin-like growth factor-I on in vivo and in vitro GH secretion}, volume={161}, ISSN={["1095-6840"]}, DOI={10.1016/j.ygcen.2009.01.026}, abstractNote={The regulation of growth hormone (GH) secretion by ghrelin during variable metabolic states is poorly understood. We examined plasma GH and ghrelin in hybrid striped bass (HSB) undergoing seasonally-based feeding and temperature manipulations. Fasting for 21 days (d) at 24 degrees C resulted in catabolism and up-regulation of plasma GH and ghrelin relative to fed controls. Continued fasting during cold-banking (14 degrees C, 90 d) resulted in a further 43-fold increase in ghrelin while GH remained elevated. A subsequent 19 day refeeding period at 24 degrees C elicited hyperphagic and compensatory growth responses, accompanied by declines in ghrelin and GH. We then tested the role of ghrelin in stimulating GH release in vivo and in vitro. Intraperitoneal injections of ghrelin resulted in dose-dependent increases in plasma GH after 6 hours (h). Ghrelin also increased GH release from HSB pituitaries during 6h incubations. Lastly, we assessed how metabolic state, ghrelin and insulin-like growth factor-I (IGF-I) affect in vitro pituitary GH release. Spontaneous GH release was 5.2-fold higher from pituitaries of fasted compared with fed animals. Ghrelin was equally effective in stimulating GH release from pituitaries of fed and starved animals, while it was ineffective in enhancing GH release from pituitaries of starved (21 d) then refed (4d) HSB. Incubation with IGF-I inhibited GH release regardless of metabolic state. These studies are the first to show that seasonally-based periods of feed deprivation and low temperature yield sustained increases in GH secretion that are likely mediated, at least partially, through elevated ghrelin, reduced IGF-I negative feedback and fasting-induced spontaneous GH release.}, number={3}, journal={GENERAL AND COMPARATIVE ENDOCRINOLOGY}, author={Picha, Matthew E. and Strom, Christina N. and Riley, Larry G. and Walker, Alicia A. and Won, Eugene T. and Johnstone, William M. and Borski, Russell J.}, year={2009}, month={May}, pages={365–372} }