Impact of Growth Hormone on Microglial and Astrocytic Function.

The role of growth hormone (GH) in the central nervous system (CNS) involves neuroprotection, neuroregeneration, formation of axonal projections, control of cognition, and regulation of metabolism. As GH induces insulin-like growth factor-1 (IGF-1) expression in many tissues, differentiating the specific functions of GH and IGF-1 in the organism is a significant challenge. The actions of GH and IGF-1 in neurons have been more extensively studied than their functions in nonneuronal cells (e.g., microglial cells). Glial cells are fundamentally important to CNS function. Microglia, astrocytes, oligodendrocytes, and tanycytes are essential to the survival, differentiation, and proliferation of neurons. As the interaction of the GH/IGF-1 axis with glial cells merits further exploration, our objective for this review was to summarize and discuss the available literature regarding the genuine effects of GH on glial cells, seeking to differentiate them from the role played by IGF-1 action whenever possible.

Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone.

AIMS: Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells. MAIN METHODS: Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. For the physiological studies, mice carrying ablation of GHR exclusively in ChAT-expressing cells were produced and possible changes in energy and glucose homeostasis were determined when consuming regular chow or high-fat diet (HFD). KEY FINDINGS: The majority of cholinergic neurons in the arcuate nucleus (60%) and dorsomedial nucleus (84%) of the hypothalamus are directly responsive to GH. Approximately 34% of pre-ganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus also exhibited GH-induced pSTAT5. GH-induced pSTAT5 in these ChAT neurons was absent in GHR ChAT knockout mice. Mice carrying ChAT-specific GHR deletion, either in chow or HFD, did not exhibit significant changes in body weight, body adiposity, lean body mass, food intake, energy expenditure, respiratory quotient, ambulatory activity, serum leptin levels, glucose tolerance, insulin sensitivity and metabolic responses to 2-deoxy-d-glucose. However, GHR deletion in ChAT neurons caused decreased hypothalamic Pomc mRNA levels in HFD mice. SIGNIFICANCE: Cholinergic neurons that regulate the metabolism are directly responsive to GH, although GHR signaling in these cells is not required for energy and glucose homeostasis. Thus, the physiological importance of GH action on cholinergic neurons still needs to be identified.

Acute Hormone Responses Subsequent to Agonist-Antagonist Paired Set vs. Traditional Straight Set Resistance Training.

Miranda, H, de Souza, JAAA, Scudese, E, Paz, GA, Salerno, VP, Vigário, PdS, and Willardson, JM. Acute hormone responses subsequent to agonist-antagonist paired set vs. traditional straight set resistance training. J Strength Cond Res 34(6): 1591-1599, 2020-The purpose of this study was to compare acute hormone responses and rating of perceived exertion (OMNI-Res) subsequent to the agonist-antagonist paired set (PS) vs. the traditional straight set (TS) resistance training method. Twelve recreationally trained men (25.7 ± 4.7 years, 173 ± 6.3 cm and 71.5 ± 6.6 kg) participated in the current study. After 10 repetition maximum (RM) load determination, each subject performed the following 2 experimental sessions in random order: TS session-3 sets of 10 repetitions at 85% of 10RM for the machine seated row and barbell bench press with 2-minute rest intervals between sets; and PS-3 sets of 10 repetitions with 85% of 10RM alternating machine seated row and barbell bench press for the total of 6 PSs with 2-minute rest intervals between sets. Total testosterone (TT), free testosterone (FT), cortisol, TT/cortisol ratio, growth hormone (GH), and blood lactate concentrations were measured before workout and immediately after workout and 15 and 30 minutes after workout. The OMNI-RES was recorded at the end of each set for both exercises within each session. Under the TS session, TT significantly increased immediately post-workout vs. the pre-workout time point. For the PS session, TT significantly decreased at 30-minute post-workout vs. the immediate post-workout time point, whereas, FT significantly increased immediately post-workout and 15-minute post-workout vs. the pre-workout time point. For the TS session, GH significantly increased immediately post-workout, and at the 15- and 30-minute post-workout time points vs. the pre-workout time point, respectively. For the PS session, GH was significantly increased immediately post-workout vs. the pre-workout time point. Blood lactate significantly increased at all post-workout time points vs. the pre-workout time point under both sessions. The cortisol and TT/cortisol ratio showed no differences between sessions. In conclusion, from an acute standpoint, the TS approach showed a tendency to cause greater disruption in hormone levels, despite the lack of significant differences vs. the PS approach at all time points. However, both strategies may promote similar acute hormone responses.

New insights of growth hormone (GH) actions from tissue-specific GH receptor knockouts in mice

ABSTRACT In order to provide new insights into the various activities of GH in specific tissues, recent advances have allowed for the generation of tissue-specific GHR knockout mice. To date, 21 distinct tissue-specific mouse lines have been created and reported in 28 publications. Targeted tissues include liver, muscle, fat, brain, bone, heart, intestine, macrophage, pancreatic beta cells, hematopoietic stem cells, and multi-tissue "global". In this review, we provide a brief history and description of the 21 tissue-specific GHR knockout mouse lines. Arch Endocrinol Metab. 2019;63(6):557-67

Central growth hormone action regulates metabolism during pregnancy.

The maternal organism undergoes numerous metabolic adaptations to become prepared for the demands associated with the coming offspring. These metabolic adaptations involve changes induced by several hormones that act at multiple levels, ultimately influencing energy and glucose homeostasis during pregnancy and lactation. Previous studies have shown that central growth hormone (GH) action modulates glucose and energy homeostasis. However, whether central GH action regulates metabolism during pregnancy and lactation is still unknown. In the present study, we generated mice carrying ablation of GH receptor (GHR) in agouti-related protein (AgRP)-expressing neurons, in leptin receptor (LepR)-expressing cells or in the entire brain to investigate the role played by central GH action during pregnancy and lactation. AgRP-specific GHR ablation led to minor metabolic changes during pregnancy and lactation. However, while brain-specific GHR ablation reduced food intake and body adiposity during gestation, LepR GHR knockout (KO) mice exhibited increased leptin responsiveness in the ventromedial nucleus of the hypothalamus during late pregnancy, although their offspring showed reduced growth rate. Additionally, both Brain GHR KO and LepR GHR KO mice had lower glucose tolerance and glucose-stimulated insulin secretion during pregnancy, despite presenting increased insulin sensitivity, compared with control pregnant animals. Our findings revealed that during pregnancy central GH action regulates food intake, fat retention, as well as the sensitivity to insulin and leptin in a cell-specific manner. Together, the results suggest that GH acts in concert with other "gestational hormones" to prepare the maternal organism for the metabolic demands of the offspring.

Acute effects of somatomammotropin hormones on neuronal components of the hypothalamic-pituitary-gonadal axis.

Growth hormone (GH) and prolactin (PRL) are known as pleiotropic hormones. Accordingly, the distribution of their receptors comprises several organs and tissues, including the central nervous system. The appropriate secretion of both hormones is essential for sexual maturation and maintenance of reproductive functions, while defects in their secretion affect puberty onset and can cause infertility. Conversely, GH therapy at a prepubertal age may accelerate puberty. On the other hand, hyperprolactinemia is a frequent cause of infertility. While the action of PRL in some central components of the Hypothalamic-Pituitary-Gonadal (HPG) axis, such as the kisspeptin neurons, has been well documented, the possible effects of GH in the hypothalamus are still elusive. Thus, the present study was designed to investigate whether somatomammotropin hormones are able to modulate the activity of critical neuronal components of the HPG axis, including kisspeptin neurons and cells of the ventral premammillary nucleus (PMv). Our results revealed that GH effects in kisspeptin neurons of the anteroventral periventricular and rostral periventricular nuclei or in PMv neurons relies predominantly on the recruitment of the signal transducer and activator of transcription 5 (STAT5) rather than through acute changes in resting membrane potential. Importantly, kisspeptin neurons located at the arcuate nucleus were not directly responsive to GH. Additionally, our findings further identified PMv neurons as potential targets of PRL, since PRL induces the phosphorylation of STAT5 and depolarizes PMv neurons. Combined, our data provide evidence that GH and PRL may affect the HPG axis via specific hypothalamic neurons.

New insights of growth hormone (GH) actions from tissue-specific GH receptor knockouts in mice.

In order to provide new insights into the various activities of GH in specific tissues, recent advances have allowed for the generation of tissue-specific GHR knockout mice. To date, 21 distinct tissue-specific mouse lines have been created and reported in 28 publications. Targeted tissues include liver, muscle, fat, brain, bone, heart, intestine, macrophage, pancreatic beta cells, hematopoietic stem cells, and multi-tissue "global". In this review, we provide a brief history and description of the 21 tissue-specific GHR knockout mouse lines. Arch Endocrinol Metab. 2019;63(6):557-67.

Efecto de Estradiol y Testosterona sobre la activación de la vía JAK2/STAT5 inducida por hormona de crecimiento / Estradiol and Testosterone effect on the activation of the JAK2/STAT5 pathway induced by growth hormone

Abstract: Sex hormones play a major role during pubertal growth. Estradiol (E2) and testosterone (T) levels progressively increase during puberty and in the presence of growth hormone (GH), growth velocity increases. Understanding the interactions between sex hormones and GH, may optimize the treatment of pubertal children with growth disorders. The aim of our study was to investigate possible molecular mechanisms which might potentiate longitudinal growth during puberty due to E 2or T combined with GH. We evaluated the GH/JAK2/STAT5 signaling pathway in the human hepatoma cell line HEPG2. Our results suggest that sex hormones potentiate the GH signaling pathway in a dose dependent fashion. Relatively low concentrations of E 2associated with GH induce a substantial activation of the GH pathway, whereas relatively high concentrations of T associated with GH produce a similar effect. These findings are concordant with the physiology of the pubertal growth spurt, which is an early event in girls (when E 2 circulating levels are low), and a late event in boys (when T circulating levels are high).

Resumen: Las hormonas sexuales, modulan el crecimiento durante la pubertad. Los niveles de estradiol (E2) y testosterona (T) aumentan progresivamente durante la pubertad y en combinación con la hormona de crecimiento (GH), producen un incremento en la velocidad de crecimiento en este período conocido como el "estirón puberal". El estudio de la interacción entre las hormonas sexuales y la GH, es de gran importancia para optimizar el tratamiento de niños(as) con alteraciones del crecimiento durante la pubertad. El objetivo de nuestro estudio fue investigar los posibles mecanismos que podrían potenciar el crecimiento longitudinal durante la pubertad, en especial las interacciones entre E 2o T en combinación con GH. Se evaluó la activación de la vía de señalización GH/JAK2/STAT5 frente al estímulo combinado con estas hormonas en cultivos celulares de hepatoma humana HEPG2. Nuestros resultados sugieren que existe un efecto potenciador de las hormonas sexuales sobre la vía de señalización de GH. Observamos que concentraciones relativamente bajas de E2 junto con GH producen una clara activación de la vía de señalización para GH, mientras que concentraciones relativamente altas de T junto con GH producen una activación similar. Estos hallazgos son concordantes con la fisiología del estirón puberal, que es más precoz en niñas (cuando los niveles circulantes de E2 son bajos), y más tardíos en varones (cuando los niveles circulantes de T son altos).

Resident murine macrophage migration and phagocytosis are modulated by growth hormone.

Growth hormone (GH) plays a physiological role in the immune system. In macrophages, GH enhances the production of hydrogen peroxide, superoxide anions, nitric oxide, cytokines, and chemokines, including interferon-γ and macrophage inflammatory protein-1α. However, some of the effects of GH stimulation on the biological functions of macrophages remain to be elucidated. Herein, we showed that in vivo GH treatment resulted in decreased expression of VLA-5 and VLA-6 integrins on the macrophage surface, accompanied by a reduction in macrophage adhesion to extracellular matrix (ECM) ligands, fibronectin, and laminin. Additionally, a decrease in macrophage adhesion to laminin was observed when the cells were treated in vitro with GH. In transwell migration assays, GH-treated macrophages showed increased migration after 6 h. Although in vitro GH treatment did not influence the phagocytic activity of macrophages, when the treatment was performed in vivo, peritoneal macrophages from GH-treated mice showed a higher percentage of phagocytosis and higher phagocytic capacity than cells from control animals. These results led us to analyse the role of insulin-like growth factor-1 (IGF-1), a GH stimulated factor, on macrophage phagocytosis. We observed an increase in phagocytic activity when J774 murine macrophages were treated with IGF-1 for 24 h. Our results revealed an important role for GH in resident macrophage migration and phagocytic activity. Specifically, we demonstrate that IGF-1 may be the GH stimulated factor that induces macrophage phagocytosis in vivo.

Efeito da somatotropina bovina recombinante (rbST) sobre a concentração espermática de ovinos Santa Inês / Effect of recombinant bovine somatotropin (rbST) in sperm concentration of sheep Santa Inês

This study aimed to evaluate among the seminal characteristics, sperm concentration of Santa Inessheep, aged 22-36 months treated with recombinant bovine somatotropin (rbST). Divided into groups randomly:GI (2mL / 0.9% NaCl), G-II (100mg / rbST) and G-III (125mg / rbST), receiving treatments subcutaneouslyevery 14 days (D0,14,28, 42,56,70). They were measured scrototesticular biometrics. The ejaculates werecollected by artificial vagina, with dummy sheep, and analyzed for volume, vortex, motility, vigor, morphologyand sperm concentration. There was no significant difference (P > 0.05) in PE (30,1cm) and in almost all semenparameters. However, on sperm concentration (sperm / mL) in G-III, there was an increase (787.69 ± 480.72)compared to groups. It was concluded that the dose of 125mg / rbST increases the sperm concentration of ovineSanta Ines.

Efeito da somatotropina bovina recombinante (rbST) sobre a concentração espermática de ovinos Santa Inês / Effect of recombinant bovine somatotropin (rbST) in sperm concentration of sheep Santa Inês

This study aimed to evaluate among the seminal characteristics, sperm concentration of Santa Inessheep, aged 22-36 months treated with recombinant bovine somatotropin (rbST). Divided into groups randomly:GI (2mL / 0.9% NaCl), G-II (100mg / rbST) and G-III (125mg / rbST), receiving treatments subcutaneouslyevery 14 days (D0,14,28, 42,56,70). They were measured scrototesticular biometrics. The ejaculates werecollected by artificial vagina, with dummy sheep, and analyzed for volume, vortex, motility, vigor, morphologyand sperm concentration. There was no significant difference (P > 0.05) in PE (30,1cm) and in almost all semenparameters. However, on sperm concentration (sperm / mL) in G-III, there was an increase (787.69 ± 480.72)compared to groups. It was concluded that the dose of 125mg / rbST increases the sperm concentration of ovineSanta Ines.(AU)

Hormônio do crescimento e suas implicações no período pós-parto de bovinos / Growth hormone and its actuation in the post-partum period

O hormônio do Crescimento (GH) é um polipeptídeo envolvido no metabolismo geral do organismo de diferentes espécies de vertebrados. Este hormônio atua no crescimento corporal, na manutenção da homeostasia do organismo no período de jejum e de atividade física, na lactação e também na reprodução. Pode atuar diretamente nos órgãos ou de forma indireta por meio do fator de crescimento semelhante à insulina (IGF). O objetivo deste trabalho é fazer uma revisão de literatura sobre a síntese de GH e sua regulação neuroendócrina, sobre sua atuação no metabolismo, no crescimento e na reprodução de diferentes vertebrados. Dando destaque para a espécie bovina, devido à importância do GH no período pós-parto desta espécie.

Growth hormone (GH) is a polypeptide involved in the general metabolism of the body of different vertebrate species. This hormone acts on body growth, maintenance of homeostasis during fasting and physical activity, lactation and also on reproduction. It can act directly on organs or indirectly through insulin-like growth factor (IGF). The objective of this study is to review the literature regarding the synthesis and neuroendocrine regulation of GH, but the focus will be the bovine species, due to the importance of GH in the postpartum period of this species.

Hormônio do crescimento e suas implicações no período pós-parto de bovinos / Growth hormone and its actuation in the post-partum period

O hormônio do Crescimento (GH) é um polipeptídeo envolvido no metabolismo geral do organismo de diferentes espécies de vertebrados. Este hormônio atua no crescimento corporal, na manutenção da homeostasia do organismo no período de jejum e de atividade física, na lactação e também na reprodução. Pode atuar diretamente nos órgãos ou de forma indireta por meio do fator de crescimento semelhante à insulina (IGF). O objetivo deste trabalho é fazer uma revisão de literatura sobre a síntese de GH e sua regulação neuroendócrina, sobre sua atuação no metabolismo, no crescimento e na reprodução de diferentes vertebrados. Dando destaque para a espécie bovina, devido à importância do GH no período pós-parto desta espécie.(AU)

Growth hormone (GH) is a polypeptide involved in the general metabolism of the body of different vertebrate species. This hormone acts on body growth, maintenance of homeostasis during fasting and physical activity, lactation and also on reproduction. It can act directly on organs or indirectly through insulin-like growth factor (IGF). The objective of this study is to review the literature regarding the synthesis and neuroendocrine regulation of GH, but the focus will be the bovine species, due to the importance of GH in the postpartum period of this species.(AU)

Simvastatin impairs growth hormone-activated signal transducer and activator of transcription (STAT) signaling pathway in UMR-106 osteosarcoma cells.

Recent studies have demonstrated that statins reduce cell viability and induce apoptosis in various types of cancer cells. The molecular mechanisms underlying these effects are poorly understood. The JAK/STAT pathway plays an important role in the regulation of proliferation and apoptosis in many tissues, and its deregulation is believed to be involved in tumorigenesis and cancer. The physiological activation of STAT proteins by GH is rapid but transient in nature and its inactivation is regulated mainly by the expression of SOCS proteins. UMR-106 osteosarcoma cells express a GH-responsive JAK2/STAT5 signaling pathway, providing an experimental model to study the influence of statins on this system. In this study we investigated the actions of simvastatin on cell proliferation, migration, and invasion on UMR-106 cells and examined whether alterations in GH-stimulated JAK/STAT/SOCS signaling may be observed. Results showed that treatment of osteosarcoma cells with simvastatin at 3 to 10 µM doses decreases cell proliferation, migration, and invasion in a time- and dose-dependent manner. At the molecular level, although the mechanisms used by simvastatin are not entirely clear, the effect of the statin on the reduction of JAK2 and STAT5 phosphorylation levels may partially explain the decrease in the GH-stimulated STAT5 transcriptional activity. This effect correlated with a time- and dose-dependent increase of SOCS-3 expression levels in cells treated with simvastatin, a regulatory role that has not been previously described. Furthermore, the finding that simvastatin is capable of inducing SOCS-3 and CIS genes expression shows the potential of the JAK/STAT pathway as a therapeutic target, reinforcing the efficacy of simvastatin as chemotherapeutic drug for the treatment of osteosarcoma.

GH overexpression decreases spermatic parameters and reproductive success in two-years-old transgenic zebrafish males.

Growth hormone (GH) transgenesis has been postulated as a biotechnological tool for improving growth performance in fish aquaculture. However, GH is implied in several other physiological processes, and transgenesis-induced GH excess could lead to unpredictable collateral effects, especially on reproductive traits. Here, we have used two-years-old transgenic zebrafish males to evaluate the effects of GH-transgenesis on spermatic parameters and reproductive success. Transgenic spermatozoa were analyzed in terms of motility, motility period, membrane integrity, mitochondrial functionality, DNA integrity, fertility and hatching rate. We have also performed histological analyses in gonad, in order to verify the presence of characteristic cell types from mature testes. The results obtained have shown that, even in transgenic testes present in all cells in normal mature gonads, a significant general decrease was observed in all spermatic and reproductive parameters analyzed. These outcomes raise concerns about the viability of GH-transgenesis appliance to aquaculture and the environmental risks at the light of Trojan gene hypothesis.

Height deficit and impairment of the GH/IGF-1 axis in patients treated for acute lymphoblastic leukemia during childhood.

BACKGROUND: Endocrine complications after acute lymphoblastic leukemia (ALL) are common. METHODS: Final height, GH/IGF-1 axis, and body mass index were analyzed after 13.7 (7.0-20.7) years from diagnosis in 34 boys aged <12 years at diagnosis and 41 girls <10 years at diagnosis. A modified German BFM-83 ALL protocol included (n = 42) or did not include (n = 33) prophylactic cranial irradiation. In 27 patients, GH after insulin tolerance test, IGF-1, cortisol, free T(4) and estradiol/testosterone were determined. RESULTS: Final height was significantly reduced (mean Z-score for height between final height and diagnosis, ΔHAZ = -0.61, p = 0.0001). At that point, 3 patients were obese (4%) and 17 were overweight (22.7%). Patients aged ≤ 4 years at diagnosis and those irradiated had a greater loss in final height (p = 0.001 and p = 0.008, respectively). Abnormalities in GH/IGF-1 axis were observed in 4 patients: 3 had a GH peak <6 ng/ml and 1 had a serum IGF-1 concentration <25 ng/ml. Growth deficit was significantly higher in patients with hormonal deficiency (p = 0.006). CONCLUSIONS: Treatment of ALL during childhood is associated with final height deficit. Young age at diagnosis and radiotherapy were the major risk factors. GH/IGF-1 deficiency was found particularly in irradiated patients, even though it was detected in 1 non-irradiated patient.

[Critical aspects of peptide hormone abuse in exercise and sports: an update]. / Aspectos críticos do abuso de hormônios protéicos no exercício e no esporte: atualização.

The hormonal abuse in physical exercise practioners is very common. Many pleople believe these substances can promote skeletal muscle hyperthrophy and improve physical fitness without health damaging effects. However, this is another myth that science unmasked. This article updates information regarding abuse of insulin, growth hormone, thyroid hormones, and erythropoitin. The peptide hormone abuse can cause motor paralysis, skeletal muscle damage and loss, diabetes mellitus, hypothyroidism, arterial hypertension, sweating, headaches, vomiting and enhances the risk for atherosclerosis, thrombosis, osteoporosis, and cancer.

El abuso de hormonas en practicantes de ejercicios físicos es muy difundido. Muchas personas creen que estas sustancias pueden producirla hipertrofia muscular y mejorar el estado físico sin traer daños a la salud. Sin embargo, esto es sólo un mito desacreditado por la ciencia. En este artículo se actualizan las informaciones sobre el abuso de la insulina, hormonas del crecimiento, hormonas tiroideas yeritropoyetina. El abuso de hormonas de la proteína (péptido) puede causar parálisis motora, lesión y pérdida de la masa muscular, la diabetes mellitus, hipotiroidismo, hipertensión arterial, sudoración, dolor de cabeza, vómitos y aumenta el riesgo de arterioesclerosis, trombosis, osteoporosis y cáncer. Palabras-clave: IGF-1, insulina, diabetes, hipertensión, hipotiroidismo.

Neuro-protective effects of growth hormone (GH) after hypoxia-ischemia injury in embryonic chicken cerebellum.

Neuroprotection is a mechanism within the central nervous system (CNS) that protects neurons from damage as a result of a severe insult. It is known that growth hormone (GH) is involved in cell survival and may inhibit apoptosis in several cell types, including those of the CNS. Both GH and GH-receptor (GHR) genes are expressed in the cerebellum. Thus, we investigated the possible neuroprotective role of GH in this organ, which is very sensitive to hypoxic/ischemic conditions. Endogenous GH levels increased in the brain and cerebellum (30% and 74%, respectively) of 15-day-old chicken embryos exposed to hypoxia during 24h compared to normoxia. In primary embryonic cerebellar neuron cultures treated under hypoxia (0.5% O(2)) and low glucose (1g/L) conditions (HLG) for 1h, GH levels increased 1.16-fold compared to the control. The addition of 1nM recombinant chicken GH (rcGH) to cultures during HLG increased cell viability (1.7-fold) and the expression of Bcl-2 (1.67-fold); in contrast the caspase-3 activity and the proportion of apoptotic cells decreased (37% and 54.2%, respectively) compared to HLG. rcGH activated the PI3K/Akt pathway both under normoxic and HLG conditions, increasing the proportion of phosphorylated Akt (1.7- and 1.4-fold, respectively). These effects were abolished by wortmannin and by immunoneutralization, indicating that GH acts through this signaling pathway. Furthermore, the 15-kDa GH variant (10nM) significantly increased cell viability and decreased caspase-3 activity during HLG condition. Thus GH may act as a paracrine/autocrine neuroprotective factor that preserves cellular viability and inhibits apoptotic cell death.

Growth hormone transgenesis affects osmoregulation and energy metabolism in zebrafish (Danio rerio).

Growth hormone (GH) transgenic fish are at a critical step for possible approval for commercialization. Since this hormone is related to salinity tolerance in fish, our main goal was to verify whether the osmoregulatory capacity of the stenohaline zebrafish (Danio rerio) would be modified by GH-transgenesis. For this, we transferred GH-transgenic zebrafish (T) from freshwater to 11 ppt salinity and analyzed survival as well as relative changes in gene expression. Results show an increased mortality in T versus non-transgenic (NT) fish, suggesting an impaired mechanism of osmotic acclimation in T. The salinity effect on expression of genes related to osmoregulation, the somatotropic axis and energy metabolism was evaluated in gills and liver of T and NT. Genes coding for Na(+), K(+)-ATPase, H(+)-ATPase, plasma carbonic anhydrase and cytosolic carbonic anhydrase were up-regulated in gills of transgenics in freshwater. The growth hormone receptor gene was down-regulated in gills and liver of both NT and T exposed to 11 ppt salinity, while insulin-like growth factor-1 was down-regulated in liver of NT and in gills of T exposed to 11 ppt salinity. In transgenics, all osmoregulation-related genes and the citrate synthase gene were down-regulated in gills of fish exposed to 11 ppt salinity, while lactate dehydrogenase expression was up-regulated in liver. Na(+), K(+)-ATPase activity was higher in gills of T exposed to 11 ppt salinity as well as the whole body content of Na(+). Increased ATP content was observed in gills of both NT and T exposed to 11 ppt salinity, being statistically higher in T than NT. Taking altogether, these findings support the hypothesis that GH-transgenesis increases Na(+) import capacity and energetic demand, promoting an unfavorable osmotic and energetic physiological status and making this transgenic fish intolerant of hyperosmotic environments.