Immunoreactive Growth Hormone Research Articles

Localization, distribution and expression of growth hormone in the brain of Asian Catfish, Clarias batrachus.

Intense immunoreactivity was observed in several neurons of the nucleus preopticus (NPO) located in the preoptic area (POA), in addition to several GH cells in the proximal pars distalis (PPD) of the pituitary gland of Clarias batrachus. The immunoreactive cells were located in the paraventricular as well as supraoptic subdivisions of the NPO. GH immunoreactive fibers projecting from the neurons were traced caudally to the pituitary gland via the conspicuous preoptico-hypophysial tract (PHT) in the ventral tuberal area to the neurohypophysis of the pituitary. Apart from these immunoreactive fibers in the preoptico-hypophysial tract, some fine caliber fiber probably arising from the neurons located dorsally in the NPO also showed GH immunoreactivity, and these fibers constituted an independent tract. Bilaterally, it extended caudally through the dorsal hypothalamus almost as far as the saccus vasculosus where it curved sharply to descend into the caudal tuberal region and finally entered into the pituitary gland. The fibers of this tract were mainly distributed in the rostral pars distalis (RPD). This tract is quite distinct from the preoptico-hypophysial tract and herein called as the accessory preoptico-hypophysial tract (APHT). Expression of GH mRNA in the NPO was found 65-fold more than that of the control region, rostral cerebellum. These results altogether suggest that GH secreted by NPO neurons might serve as a neuro-modulatory role in the brain of C. batrachus. Transportation of GH to the pituitary via two independent tracts may represent the duality of neuroendocrine function. The present study underscores the possibility that GH in the brain of vertebrates may be a phylogenetically conserved phenomenon and provide clues to our understanding of the evolutionary course taken by the hormone.

Acute Resistance Exercise on Bioactive and Immunoreactive Growth Hormone in Women.

PURPOSE: The purpose was to determine the differences between trained and untrained women for concentrations of BGH and IGH in response to acute resistance exercise. METHODS: Untrained recreationally active women (UT) (N= 12), mean ± SD: 24 ± 2.4 yr, 167 ± 6.3 cm, 68.8 ± 7.3 kg, 27.3 ± 4.0% body fat, and trained women (TW) (N= 12), 25 ± 3.4 yr, 168 ± 7.3 cm, 69.8 ± 6.3 kg, 19.3 ± 2.7% body fat gave informed consent. Trained status was determined by participation in aerobic/resistance training programs for at least 1 year. The women were tested for 1 repetition maximum strength (1 RM) in the squat and were familiarized with the squat test protocol that consisted of 6 sets of 10 repetitions at 75% of their 1 RM with 2 minutes rest between sets. Testing was performed during the early follicular phase between 0630 and 1100 after an 8- to 12-h fast. Pre-exercise blood samples were obtained via standard venipuncture 15 min before the test and post-exercise samples were obtained immediately after the resistance training test protocol. Plasma was collected and assayed for IGH using polyclonal and monoclonal assays. Total BGH was assayed using the rat tibial line in vivo bioassay. A two-way analysis of variance (2 X 2) for group and time were used to analyze the data, with p ≤ 0.05 defined as significance. RESULTS: The TW were significantly stronger than the UT in the squat. Both groups significantly increased their IGH concentrations post-exercise, with the monoclonal assay showing significantly higher values than polyclonal assays and TW showing greater post-exercise values than UT [Monoclonal: (TW: 5 ± 2 to 19 ± 3 μg/L-1, UT: 4.9 ± 2 to 10.2 ± 3.0 μg/L-1)]. BGH did not increase pre to post exercise in either group, yet TW had significantly higher pre-exercise and post-exercise BGH (3900 ± 233 to 4100 ± 323 μg/L-1) than UT women (2500 ± 333 to 2100 ± 223 μg/L-1). BGH was significantly higher than IGH assays at all time points. CONCLUSIONS: Resistance training impacts both the BGH and IGH secretion patterns from the anterior pituitary gland. IGH is acutely increased in response to resistance training in women, with an even higher response in trained women. BGH is chronically higher in trained women than untrained, but shows no response with acute resistance training. These findings may be more responsible for GH’s role in chronic resistance training adaptations.

Influence of Body Fat on Bioactive and Immunoreactive Growth Hormone Exercise Responses in Women

Influence of Body Fat on Bioactive and Immunoreactive Growth Hormone Exercise Responses in Women

Foxo1 Is Required for Normal Somatotrope Differentiation.

The etiology for half of congenital hypopituitarism cases is unknown. Our long-term goal is to expand the molecular diagnoses for congenital hypopituitarism by identifying genes that contribute to this condition. We have previously shown that the forkhead box transcription factor, FOXO1, is present in approximately half of somatotropes at embryonic day (e) 18.5, suggesting it may have a role in somatotrope differentiation or function. To elucidate the role of FOXO1 in somatotrope differentiation and function, Foxo1 was conditionally deleted from the anterior pituitary (Foxo1Δpit). Uncommitted progenitor cells are maintained and able to commit to the somatotrope lineage normally based on the expression patterns of Sox2, a marker of uncommitted pituitary progenitors, and Pou1f1 (also known as Pit1), which marks committed progenitors. Interestingly, Foxo1Δpit embryonic mice exhibit delayed somatotrope differentiation as evidenced by an almost complete absence of GH immunoreactivity at e16.5 and reduced expression of Gh at e18.5 and postnatal day (P) 3. Consistent with this conclusion, expression of GHRH receptor, a marker of terminally differentiated somatotropes, is significantly reduced at e18.5 and P3 in the absence of FOXO1. The mechanism of FOXO1 regulation of somatotrope differentiation may involve the basic helix-loop-helix transcription factor, Neurod4, which has been implicated in somatotrope differentiation and is significantly reduced in Foxo1Δpit mice. Foxo1Δpit mice do not exhibit growth defects, and at P21 their pituitary glands exhibit a normal distribution of somatotropes. These studies demonstrate that FOXO1 is important for initial somatotrope specification embryonically but is dispensable for postnatal somatotrope expansion and growth.

Growth hormone reverses excitotoxic damage induced by kainic acid in the green iguana neuroretina

It is known that growth hormone (GH) is expressed in extrapituitary tissues, including the nervous system and ocular tissues, where it is involved in autocrine/paracrine actions related to cell survival and anti-apoptosis in several vertebrates. Little is known, however, in reptiles, so we analyzed the expression and distribution of GH in the eye of green iguana and its potential neuroprotective role in retinas that were damaged by the intraocular administration of kainic acid (KA). It was found, by Western blotting, that GH-immunoreactivity (GH-IR) was expressed as two isoforms (15 and 26kDa, under reducing conditions) in cornea, vitreous, retina, crystalline, iris and sclera, in varying proportions. Also, two bands for the growth hormone receptor (GHR)-IR were observed (70 and 44kDa, respectively) in the same tissues. By immunofluorescence, GH-IR was found in neurons present in several layers of the neuroretina (inner nuclear [INL], outer nuclear [ONL] and ganglion cell [GCL] layers) as determined by its co-existence with NeuN, but not in glial cells. In addition, GH and GHR co-expression was found in the same cells, suggesting paracrine/autocrine interactions. KA administration induced retinal excitotoxic damage, as determined by a significant reduction of the cell density and an increase in the appearance of apoptotic cells in the INL and GCL. In response to KA injury, both endogenous GH and Insulin-like Growth Factor I (IGF-I) expression were increased by 70±1.8% and 33.3±16%, respectively. The addition of exogenous GH significantly prevented the retinal damage produced by the loss of cytoarchitecture and cell density in the GCL (from 4.9±0.79 in the control, to 1.45±0.2 with KA, to 6.35±0.49cell/mm2 with KA+GH) and in the INL (19.12±1.6, 10.05±1.9, 21.0±0.8cell/mm2, respectively) generated by the long-term effect of 1mM KA intraocular administration. The co-incubation with a specific anti-GH antibody, however, blocked the protective effect of GH in GCL (1.4±0.23cell/mm2) and INL (11.35±1.06), respectively. Furthermore, added GH induced an increase of 90±14% in the retinal IGF-I concentration and the anti-GH antibody also blocked this effect. These results indicate that GH and GHR are expressed in the iguana eye and may be able to exert, either directly of mediated by IGF-I, a protective mechanism in neuroretinas that suffered damage by the administration of kainic acid.

Role of stress proteins and hormones in bioregulation of ontogeny

In this short review article we tried to overview diffusely spread data on the role of stress proteins and hormones in ontogeny. The work presented here is a product of our long-term studies beginning from the middle of eighties of the last century and performed both in Russia and Brazil. It involves the results obtained with the use of experimental models on laboratory animals in vivo and in vitro, as well as later theoretical research in world literature databases. In experimental studies we used laboratory rats of different age groups and primary cultures of pituitary and liver cells for evaluating respectively body and organ growth and production of immunoreactive growth hormone (GH) and serum albumin (SA), as well as biosynthesis of DNA, total RNA and protein. The results obtained, showing important role of glucocorticoids (GC) in regulation of perinatal pituitary and liver functions and postnatal growth, were reinterpreted by us recently in the frame of DOHaD concept and as related to perinatal imprinting/programming phenomena. It is concluded that the present moment is quite appropriate for the widening of our studies both to the side of early embryonal development and in direction to aging, thus completing the whole cycle of life history / course research, as referred to stress proteins and hormones.

Expression and ontogeny of growth hormone (Gh) in the protogynous hermaphroditic ricefield eel (Monopterus albus).

Growth hormone (GH) is a single-chain polypeptide hormone mainly secreted by somatotropes of the anterior pituitary gland and is an important regulator of somatic growth in vertebrates including teleosts. In this study, a polyclonal antiserum against ricefield eel Gh was generated and the expression of Gh at the mRNA and protein levels was analyzed. Both RT-PCR and western blot analysis showed that Gh was predominantly expressed in the pituitary glands of ricefield eels. The immunoreactive Gh signals were localized to the multicellular layers of the adenohypophysis adjacent to the neurohypophysis in ricefield eels. Ontogenetic analysis showed that immunoreactive Gh signals could be detected in the pituitary glands of ricefield eel embryos as early as 3 days post-fertilization. During the sex change from female to male, the levels of the immunoreactive Gh signals in the pituitary glands of the ricefield eels peaked at the intersexual stage. These results suggest that Gh in the pituitary glands may be associated with embryonic development before hatching, as well as with the sex change in the adult ricefield eels, possibly via the classical endocrine manner.

Acute resistance exercise stimulates sex-specific dimeric immunoreactive growth hormone responses

PurposeWe sought to determine if an acute heavy resistance exercise test (AHRET) would elicit sex-specific responses in circulating growth hormone (GH), with untreated serum and serum treated with a reducing agent to break disulfide-bindings between GH dimers. Methods19 untrained participants (nine men and ten women) participated in an acute heavy resistance exercise test using the back squat. Blood samples were drawn before exercise (Pre), immediate post (IP), +15min (+15), and +30min (+30) afterwards. Serum samples were chemically reduced using glutathione (GSH). ELISAs were then used to compare immunoreactive GH concentrations in reduced (+GSH) and non-reduced (−GSH) samples. Data were analyzed using a three-way (2 sex×2 treatment×4 time) mixed methods ANOVA, with significance set at p≤0.05. ResultsGSH reduction resulted in increased immunoreactive GH concentrations when compared to non-reduced samples at Pre (1.68±0.33μg/L vs 1.25±0.25μg/L), IP (7.69±1.08μg/L vs 5.76±0.80μg/L), +15min (4.39±0.58μg/L vs 3.24±0.43μg/L), and +30min (2.35±0.49μg/L vs 1.45±0.23μg/L). Also, women demonstrated greater GH responses compared to men, and this was not affected by reduction. ConclusionsHeavy resistance exercise increases immunoreactive GH dimer concentrations in men and women, with larger increases in women and more sustained response in men. The physiological significance of a sexually dimorphic GH response adds to the growing literature on aggregate GH and may be explained by differences in sex hormones and the structure of the GH cell network.

The Acute Hormonal Response to the Kettlebell Swing Exercise

The purpose of this investigation was to examine the acute hormonal response to the kettlebell swing exercise. Ten recreationally resistance trained men (age, 24 ± 4 years; height, 175 ± 6 cm; body mass, 78.7 ± 9.9 kg) performed 12 rounds of 30 seconds of 16 kg kettlebell swings alternated with 30 seconds of rest. Blood samples were collected before (PRE), immediately after (IP), and 15 (P15) and 30 minutes after exercise (P30) and analyzed for testosterone (T), immunoreactive growth hormone, cortisol (C), and lactate concentrations. Heart rate and rating of perceived exertion were measured at the end of each round. Testosterone was significantly higher (p ≤ 0.05) at IP than at PRE, P15, or P30 (PRE: 28 ± 3; IP: 32 ± 4; P15: 29 ± 3; P30: 27 ± 3 nmol·L). Growth hormone was higher at IP, P15, and P30 than at PRE (PRE: 0.1 ± 0.1; IP: 1.8 ± 1.2; P15: 2.1 ± 1.1; P30: 1.6 ± 1.3 μg·L). Cortisol was higher at IP and P15 than at PRE and P30 (PRE: 617 ± 266; IP: 894 ± 354; P15: 875 ± 243; P30: 645 ± 285 nmol·L). Lactate was higher at IP, P15, and P30 than at PRE (PRE: 1.1 ± 0.5; IP: 7.0 ± 3.0; P15: 4.0 ± 2.7; P30: 2.5 ± 1.8 mmol·L). Heart rate increased progressively from 57 ± 12 at PRE to 170 ± 10 at IP. The exercise protocol produced an acute increase in hormones involved in muscle adaptations. Thus, the kettlebell swing exercise might provide a good supplement to resistance training programs.

P.5.a.006 Flavopiridol, an inhibitor of cyclin-dependent kinase 4, reverses cognitive deficits induced by β-amyloid peptide 1–42

It is known that growth hormone (GH) is expressed in extrapituitary tissues, including the nervous system and ocular tissues, where it is involved in autocrine/paracrine actions related to cell survival and anti-apoptosis in several vertebrates. Little is known, however, in reptiles, so we analyzed the expression and distribution of GH in the eye of green iguana and its potential neuroprotective role in retinas that were damaged by the intraocular administration of kainic acid (KA). It was found, by Western blotting, that GH-immunoreactivity (GH-IR) was expressed as two isoforms (15 and 26 kDa, under reducing conditions) in cornea, vitreous, retina, crystalline, iris and sclera, in varying proportions. Also, two bands for the growth hormone receptor (GHR)-IR were observed (70 and 44 kDa, respectively) in the same tissues. By immunofluorescence, GH-IR was found in neurons present in several layers of the neuroretina (inner nuclear [INL], outer nuclear [ONL] and ganglion cell [GCL] layers) as determined by its co-existence with NeuN, but not in glial cells. In addition, GH and GHR co-expression was found in the same cells, suggesting paracrine/autocrine interactions. KA administration induced retinal excitotoxic damage, as determined by a significant reduction of the cell density and an increase in the appearance of apoptotic cells in the INL and GCL. In response to KA injury, both endogenous GH and Insulin-like Growth Factor I (IGF-I) expression were increased by 70 ± 1.8% and 33.3 ± 16%, respectively. The addition of exogenous GH significantly prevented the retinal damage produced by the loss of cytoarchitecture and cell density in the GCL (from 4.9 ± 0.79 in the control, to 1.45 ± 0.2 with KA, to 6.35 ± 0.49 cell/mm2 with KA + GH) and in the INL (19.12 ± 1.6, 10.05 ± 1.9, 21.0 ± 0.8 cell/mm2, respectively) generated by the long-term effect of 1 mM KA intraocular administration. The co-incubation with a specific anti-GH antibody, however, blocked the protective effect of GH in GCL (1.4 ± 0.23 cell/mm2) and INL (11.35 ± 1.06), respectively. Furthermore, added GH induced an increase of 90 ± 14% in the retinal IGF-I concentration and the anti-GH antibody also blocked this effect. These results indicate that GH and GHR are expressed in the iguana eye and may be able to exert, either directly of mediated by IGF-I, a protective mechanism in neuroretinas that suffered damage by the administration of kainic acid.

The influence of age and exercise modality on growth hormone bioactivity in women

ObjectivePrior research has indicated that the loss of skeletal muscle mass and bone mineral density observed with aging is related to the prominent age-related decline in the concentration of serum growth hormone (GH). However, there is limited data on the effects of aging on GH responses to acute bouts of heavy resistance exercise (HRE) and aerobic exercise (AE). DesignThe present investigation examined the effects of a HRE protocol and an AE protocol on immunoreactive GH (IGH) and bioactive GH (BGH) in active young and old women. ResultsOlder women had a diminished serum IGH response to both the HRE and AE protocols compared to the younger women, however a similar response was not observed in serum BGH. Additionally, the HRE protocol elicited a greater BGH response than the AE protocol exclusively in the younger group. ConclusionsRegardless of exercise mode, aging induces an increase in growth hormone polymerization that specifically results in a loss of serum growth hormone immunoreactivity without a concurrent loss of serum growth hormone bioactivity. The greater BGH response to the HRE protocol found in the younger group can be attributed to an unknown serum factor of molecular weight between 30 and 55kD that either potentiated growth hormone bioactivity in response to HRE or inhibited growth hormone bioactivity in response to AE.

Establishment and characterization of dairy cow growth hormone secreting anterior pituitary cell model

A dairy cow anterior pituitary cell (DCAPC) model was established in vitro for the study of growth hormone (GH) synthesis and secretion in the anterior pituitary gland of the dairy cow. Pituitary glands were obtained from Holstein dairy cows' heads cut by electric saw, and the posterior pituitary glands were removed to obtain integrated anterior pituitary glands. Immunohistochemistry assay of GH in the anterior pituitary glands showed that most somatotrophs were located within the lateral wings of the anterior pituitary. Tissues of the lateral wings of the anterior pituitary were dispersed and cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The DCAPCs displayed a monolayer, cobblestone, epithelial-like morphology which are the typical characteristics of the anterior pituitary cells. The DCAPCs were subcultured continuously over ten passages. GH immunoreactivity was present in DCAPCs at passage 10. The transcription of the bovine GH mRNA in DCAPCs at passage 10 was decreased to below 50% compared with the lateral wings of the anterior pituitary tissues. Thus, our DCAPCs model is effective for the in vitro examination of GH synthesis and secretion in the dairy cow anterior pituitary gland. The effects of transforming growth factor beta 1 (TGF-β1) and interferon-γ (IFN-γ) on the expression of GH mRNA in DCAPCs at passage 3 were also investigated. There were no obvious changes in transcription of the GH gene after treatment with TGF-β1 for 24 h, while IFN-γ increased transcription of the GH gene in a dose-dependent manner.

Development of a Bioassay System for Human Growth Hormone Determination with Close Correlation to Immunoassay

Serum growth hormone (GH) level is measured largely through immunoassays in clinical practice. However, a few cases with bioinactive and immunoreactive GH have also been reported. We describe here a new bioassay system for GH determination using the BaF/GM cell line, which proliferates in a dose-dependent manner on hGH addition; cell proliferation was blocked by anti-hGH antibody. This bioassay had the lowest detection limit (∼0.02 ng/ml) reported thus far and the highest specificity for GH. The bioassay results were compared with those of an immunoradiometric assay across 163 patient samples in various endocrine states. A close correlation (the ratio of bioactivity/immunoreactivity was 1.04 ± 0.33, mean ± SD) was observed between bioactivity and immunoreactivity in these samples. The newly developed system is a specific, sensitive, easy, and fast bioassay system for GH determination; we consider it useful for evaluating GH bioactivity in various endocrine states.

The influence of ovarian factors on the somatostatin–growth hormone system during the postnatal growth and sexual development in lambs

The aim of the study was to elucidate the effects of ovarian hormones on somatostatin in the hypothalamic neurons and growth hormone (GH) secretion during the postnatal growth and development of sheep. The study was performed on 9-week-old (infantile) lambs that were ovary-intact (OVI) or ovariectomized (OVX) at 39 days of age, and on 16-week-old (juvenile) lambs that were OVI or OVX at 88 days of age. Hormones in neurons and somatotropic cells were assayed with immunohistochemistry and radioimmunoassay. Following ovariectomy, immunoreactive somatostatin was more abundant (p<0.05) in the hypothalamus of infantile lambs, whereas in juvenile lambs it was more abundant (p<0.05) in the periventricular nucleus but reduced (p<0.01) in the median eminence. In contrast to somatostatin in the hypothalamus, the content of immunoreactive GH in the hypophysis was less in OVX infantile lambs, but greater in OVX juvenile lambs (p<0.05). Basal blood serum concentrations of GH were greater (p<0.05) in OVX infantile lambs, whereas in OVX juvenile lambs, mean and basal concentrations of GH and amplitude of GH pulses were less than in OVI lambs (p<0.05). The postnatal increase in body weight was greatest in middle-late infancy (p<0.01). The body weight did not differ (p>0.05) between OVI and OVX lambs. In conclusion, ovarian factors may inhibit the GH secretion in infantile lambs but enhance the GH secretion in juvenile lambs. Transition to puberty, as related to the growth rate, appears to be due mainly to change in gonadal influence on the somatostatin neurosecretion. A stimulation of somatostatin output in the median eminence by gonadal factors in infancy is followed by a stimulation of somatostatin accumulation after infancy. Thus, ovarian factors modulate mechanisms within the somatotropic system of lambs to synchronize the somatic growth with sexual development.

Visualization of immunoreactive growth hormone in cultured peripheral bovine lymphocytes

Growth hormone (GH) has been shown to be released by immune cells in vitro. Thus, the intracellular confinement of GH immunoreactivity was investigated in cultured bovine lymphocytes using con-focal microscopy. Peripheral blood lymphocytes from cows in early pregnancy (10–20days post insemination; pi) or during mid-pregnancy (day 110–140 pi) were harvested and cultured for 48h in presence of phytohemagglutinin-M (PHA-M) or served as controls. Thereafter, immunocytochemistry was conducted using a homologous GH-antibody. Double staining (GH-antibody and directly DYE 549 labeled CD3-antibody) was performed to classify the cells. Con-focal laser scanning was applied verifying the immunofluorescence labeling. Interestingly, the presence of GH immunoreactivity in the cytoplasm, which indicates GH synthesis, was restricted to small cells. Whereas, few T-like cells revealed surface bound GH. Lowest immunoreactivity, concerning the number of the total labeled cells as well as the intensity of labeling was recorded in early pregnancy. Stimulation with PHA-M enhanced total labeled cells in early pregnancy. In contrast, PHA-M had no such effects in mid-pregnancy. The results confirm the specific regulation of synthesis of lymphocytic GH during pregnancy in the cow. The identification of cells producing GH and the elucidation of the mechanisms underlying the expression of GH in larger number of cells during mid-pregnancy than in the early pregnancy need further investigations.

Sexual Dimorphism of Growth Hormone in the Hypothalamus: Regulation by Estradiol

GH is best known as an anterior pituitary hormone fundamental in regulating growth, differentiation, and metabolism. GH peptide and mRNA are also present in brain, in which their functions are less well known. Here we describe the distribution of GH neurons and fibers and sex differences in Gh mRNA in adult mouse brain. Cell bodies exhibiting GH immunoreactivity are distributed in many brain regions, particularly in the hypothalamus in which retrograde labeling suggests that some of these cells project to the median eminence. To determine whether Gh mRNA is sexual dimorphic, we carried out quantitative RT-PCR on microdissected brain nuclei. Ovary-intact mice had elevated Gh mRNA in the arcuate nucleus and medial preoptic area (MPOA) compared with gonad-intact males. In males, castration increased Gh mRNA in the MPOA, whereas ovariectomy decreased Gh mRNA in both regions. When gonadectomized adults of both sexes were treated with estradiol Gh mRNA increased in females but had no effect in castrated males. Tamoxifen was able to blunt the rise in Gh mRNA in response to estradiol in females. In addition, we found that estrogen receptor-α is coexpressed in GH neurons in the MPOA and arcuate nucleus. In summary, the findings reveal sexual dimorphisms in Gh gene expression in areas of the brain associated with reproduction and behavior. Interestingly, estradiol enhances Gh mRNA in females only, suggesting that multiple factors orchestrate this sexual dimorphism.

Acromegaly due to an ectopic pituitary adenoma in the clivus: case report and review of literature

Pituitary adenomas rarely originate outside the sella turcica. Ectopic locations include the suprasellar region, sphenoid sinus, cavernous sinus and clivus. We describe a 50-year-old female who presented with clinical signs and biochemical evidence of acromegaly. Pituitary MRI demonstrated a 2 mm hypointense lesion on the right side of the pituitary gland. However upon drilling of the upper clival bone to expose the sella during endoscopic transsphenoidal surgery, soft tumor-like tissue was encountered within the clivus. Exploration of the sella, including the area of hypointensity noted on preoperative imaging, did not identify any other abnormality. Immunohistochemical examination of the fully resected tumor demonstrated growth hormone immunoreactivity. Failed preoperative diagnosis of this rare ectopic GH-producing tumor was compounded by the presence of a misleading pituitary abnormality consistent with a microadenoma. The epidemiology and pertinent literature of this uncommon condition is discussed.

Immunoreactive and bioactive growth hormone responses to resistance exercise in men who are lean or obese

It has been suggested that obese individuals have a blunted growth hormone (GH) response to spontaneous and stimulated GH secretion. The present study was designed to examine the effects of a high-volume, whole body acute resistance exercise (RE) protocol on immunoreactive GH (iGH), bioactive GH (bGH), and GH-binding protein (GHBP) in sedentary lean and obese men. Nine obese (mean ± SD: 20.8 ± 2.1 yr old, 177.0 ± 4.1 cm height, 108.7 ± 15.9 kg body mass, 37.6 ± 5.29% body fat) and nine lean (20.1 ± 2.1 yr old, 177.8 ± 8.7 cm height, 71.7 ± 5.8 kg body mass, 14.7 ± 3.54% body fat) men completed an acute RE protocol (6 exercises, 3 sets of 10 repetitions at 85-95% of 10 repetitions maximum with 120- and 90-s rest periods), and blood samples were collected before, at the midpoint, and immediately after exercise and during recovery (+50, +70, and +110). In contrast to prior studies, which examined acute responses to cardiovascular exercise protocols, groups did not differ in iGH response to the exercise stimulus. However, bGH concentrations overall were significantly lower in the obese than the lean participants (P < 0.001). Additionally, obese individuals had significantly higher GHBP concentrations (P < 0.001). Results suggest that obese and lean sedentary men performing a high-volume, whole body acute RE protocol demonstrate similar increases in iGH. Blunted bGH and elevated GHBP concentrations are indicative of altered GH activity associated with obesity. Prior research findings of blunted iGH response may be attributable to RE protocols not equated on relative intensity or volume. These results underscore the complexity of pituitary biology and its related mechanisms and may have implications for exercise prescription in the treatment of obesity.

Efficacy of long-term growth hormone therapy in short children with reduced growth hormone biological activity

The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.

Increase in serum growth hormone induced by electrical stimulation of muscle combined with blood flow restriction

The purpose of this study was to investigate the role of muscle metaboreflex on exercise-induced growth hormone (GH) secretion. In order to accumulate metabolites within exercised muscle with minimized central motor activity, electromyostimulation (EMS) was performed combined with blood flow restriction (BFR). Seven men performed one-legged isometric knee extension evoked by EMS (frequency, 20Hz; pulse duration, 400μs; on-off ratio, 3-1s). Just before the exercise, proximal portion of either a stimulated thigh (ST) or a non-stimulated thigh (NT) was compressed at 150mmHg with an air-pressure cuff for the purpose of BFR. The compression was kept throughout the exercise session, and was released 2min after the end of the exercise. Two exercise sessions (ST(BFR), BFR for ST; NT(BFR), BFR for NT) were separated by 1week. ST(BFR) was aimed to accumulate metabolites within exercised muscle, whereas NT(BFR) was aimed to match mechanical stress with ST(BFR) without accumulating metabolites. Blood samples for hormonal measurements were taken from the antecubital vein before and after the exercise. Blood lactate increased immediately after the exercise in the NT(BFR), whereas it increased after the cuff deflation in the ST(BFR), suggesting that locally produced metabolites were retained and accumulated within the exercised muscle in the ST(BFR). Although serum cortisol and plasma noradrenaline increased in a similar manner in two conditions, serum immunoreactive GH (irGH) increased only in the ST(BFR). These results suggest that muscle metaboreflex plays an important role in the exercise-induced GH secretion, at least in terms of irGH secretion.