Pituitary Growth Hormone Content Research Articles

Growth hormone isoform testing in capillary dried blood spots: Results from single and multiple dose administration studies and large-scale field collections.

A multiphase study was designed to examine the detectability of human growth hormone (GH) use in capillary dried blood spots (DBS). First, 13 subjects self-injected a single, 2-mg dose of somatropin and collected capillary DBS samples for 24 h. Next, nine subjects self-injected 2-mg somatropin, six times over the course of 11 days; DBS were collected intermittently following dosing. Finally, a nondrug, large-scale field study involved DBS collections from an athlete and staff population over 3 years. All DBS samples were self-collected using the Tasso M20 device and were analyzed for the presence of GH using the WADA-approved GH isoforms test. Following the single dose, positive detection within 12 h of dosing was 86% and 56% sensitive on Kits 1 and 2, respectively. In the multidose study, detection within 12 h was 85% and 69% sensitive on Kits 1 and 2, respectively. No positives were detected outside the 12-h window following a single dose, wherein detection was 5.6% sensitive at 24-h in the multidose study. Combining the 12-h windows from both studies, 100% of samples had measurable recombinant (REC) and pituitary (PIT) GH concentrations above the assay LoD, 0.041 ng/ml. Finally, 1213 samples were collected in the large-scale field study: 189 showed REC and PIT concentrations above the LoD; none returned positive results. GH is detectable in capillary DBS using the isoforms method for 12-24 h following use. While detection is short lived, transitioning to a DBS self-collection method can allow more frequent testing and increase deterrence to GH abuse.

Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency

PurposeWe aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. MethodsWe used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. ResultsWe described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke’s pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. ConclusionOur findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function.

Interactions of amino acids and hormones regulate the balance between growth and milk protein synthesis in lactating rats fed diets differing in protein content.

Insulin-like growth factor-I (IGF-I), growth hormone (GH), and prolactin (PRL) play important roles in milk protein synthesis, and their plasma concentrations were reported to be affected by dietary protein intake. To investigate the relationship between circulating amino acid (AA) and concentrations of these hormones, 18 Wistar rats aged 14 wk were assigned to a low (LP; 9% protein), standard (SP; 21% protein), or high-protein (HP; 35% protein) diet from parturition through day 15 of lactation. Plasma, liver, pituitary gland, skeletal muscle, and mammary gland samples were collected at the end of treatment. Circulating and hepatic IGF-I concentrations increased linearly with elevated dietary protein concentrations (P < 0.0001). Rats receiving the HP diet had higher circulating GH (P < 0.01) and pituitary PRL concentrations (P < 0.0001) but lower pituitary GH concentration (P < 0.0001) relative to those in rats receiving the LP and SP diets. Pearson correlation test performed on composed data across treatments showed that several circulating AAs were correlated with circulating and tissue concentrations of IGF-I, GH, and PRL. Multiple linear regression analyses identified Leu, Gln, Ala, Gly, and Arg as the main AAs associated with hormone responses (R2 = 0.37 ~ 0.80; P < 0.05). Rats fed the LP and HP diets had greater Igf1 and Ghr gene expression in skeletal muscle than those fed the SP diets (P < 0.01). However, LP treatment decreased Prlr mRNA abundance in mammary glands as compared with the SP and HP treatments (P < 0.05). The HP diets increased AA transporter expression (P < 0.01) but decreased mammalian target of rapamycin (P < 0.05) and 70 kDa ribosomal protein S6 kinase 1 (P < 0.01) phosphorylation in mammary glands as compared with the LP and SP diets. The results of the present study suggested that several circulating AAs mediated the effects of dietary protein supply on concentrations of IGF-I, GH, and PRL, which in turn altered the metabolism status in peripheral tissues including the lactating mammary glands.

Effects of Estradiol-17β or Dihydrotestosterone on Cell Types in Equine Pituitaries Staining for Prolactin, Growth Hormone, or Both

Ovariectomized pony mares were treated with vehicle (controls), estradiol-17β (estradiol), or dihydrotestosterone (DHT) daily for 21 days in summer, and the pituitary content of prolactin and growth hormone (GH) and the numbers of cells staining immunocytochemically for prolactin (lactotropes), GH (somatotropes), or both hormones (mammosomatotropes) were assessed. Treatments did not alter (P > .1) plasma prolactin concentrations over the 21 days. Estradiol treatment increased (P < .05) the pituitary content of prolactin several-fold relative to controls and DHT-treated ponies. The number of lactotropes was also increased (P < .05), as was the number of mammosomatotropes (P < .05). Treatment with DHT did not alter (P > .1) any prolactin characteristic. The number of somatotropes was not altered by either treatment (P > .1) nor was the pituitary content of GH (P > .1). Given that the mass of prolactin accumulation in the pituitary in response to estradiol was several-fold greater than the approximate doubling of the number of lactotropes and mammosomatotropes, it appears that estradiol administration to ovariectomized pony mares stimulates not only the number of prolactin-producing cells but also the amount of prolactin production per cell.

Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat(-/-) mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat(-/-) mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat(-/-) mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat(-/-) mice.

Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice

Objective: Ghrelin is produced by the stomach, hypothalamus and pituitary. It circulates as acylated ghrelin (AG, which stimulates growth hormone (GH) secretion) and unacylated ghrelin (UAG). Acylation is mediated by the enzyme ghrelin O-acyltransferase (GOAT). In mice, pregnancy is associated with a marked increase in circulating pituitary GH. We investigated the role of AG and UAG in the surge of plasma GH concentrations in pregnant mice at the end of pregnancy. Design: Using a mouse model generated on a C57BL/6 background (wild type, WT) in which the GOAT gene has been deleted (KO), we measured plasma AG, UAG and GH concentrations and tissue (stomach, pituitary and hypothalamus) preproghrelin and GOAT mRNA in non-pregnant (NP) and pregnant (P), WT and KO mice. Results: GOAT deletion was associated with undetectable concentrations of AG. UAG concentrations were similar in all groups. In both WT and KO animals, mean GH concentrations increased 30 to 50 times during pregnancy. There was a tendency toward lower median GH concentrations in KO (301ng/mL) compared to WT (428ng/mL) mice (p=0.059). Preproghrelin expression was not affected by GOAT deletion or by pregnancy in the stomach. In contrast, pituitary and hypothalamic ghrelin gene expression were lower in KO-NP and KO-P mice compared to their WT counterparts. Conclusion: The complete absence of ghrelin acylation, which is associated with undetectable AG concentrations, does not prevent the marked increase in pituitary GH concentrations observed in pregnant mice, suggesting that AG is not the major mediator of GH secretion during pregnancy.

Daily Patterns and Adaptation of the Ghrelin, Growth Hormone and Insulin‐Like Growth Factor‐1 System Under Daytime Food Synchronisation in Rats

Daytime restricted feeding promotes the re-alignment of the food entrained oscillator (FEO). Endocrine cues which secretion is regulated by the transition of fasting and feeding cycles converge in the FEO. The present study aimed to investigate the ghrelin, growth hormone (GH) and insulin-like growth factor (IGF)-1 system because their release depends on rhythmic and nutritional factors, and the output from the system influences feeding and biochemical status. In a daily sampling approach, rats that were fed ad lib. were compared with rats on a reversed (daytime) and restricted feeding schedule by 3 weeks (dRF; food access for 2 h), also assessing the effect of acute fasting and refeeding. We undertook measurements of clock protein BMAL1 and performed somatometry of peripheral organs and determined the concentration of total, acylated and unacylated ghrelin, GH and IGF-1 in both serum and in its main synthesising organs. During dRF, BMAL1 expression was synchronised to mealtime in hypophysis and liver; rats exhibited acute hyperphagia, stomach distension with a slow emptying, a phase shift in liver mass towards the dark period and decrease in mass perigonadal white adipose tissue. Total ghrelin secretion during the 24-h period increased in the dRF group as a result of elevation of the unacylated form. By contrast, GH and IGF-1 serum concentration fell, with a modification of GH daily pattern after mealtime. In the dRF group, ghrelin content in the stomach and pituitary GH content decreased, whereas hepatic IGF-1 remained equal. The daily patterns and synthesis of these hormones had a rheostatic adaptation. The endocrine adaptive response elicited suggests that it may be associated with the regulation of metabolic, behavioural and physiological processes during the paradigm of daytime restricted feeding and associated FEO activity.

Central Dopamine D2 Receptors Regulate Growth-Hormone-Dependent Body Growth and Pheromone Signaling to Conspecific Males

Competition between adult males for limited resources such as food and receptive females is shaped by the male pattern of pituitary growth hormone (GH) secretion that determines body size and the production of urinary pheromones involved in male-to-male aggression. In the brain, dopamine (DA) provides incentive salience to stimuli that predict the availability of food and sexual partners. Although the importance of the GH axis and central DA neurotransmission in social dominance and fitness is clearly appreciated, the two systems have always been studied unconnectedly. Here we conducted a cell-specific genetic dissection study in conditional mutant mice that selectively lack DA D2 receptors (D2R) from pituitary lactotropes (lacDrd2KO) or neurons (neuroDrd2KO). Whereas lacDrd2KO mice developed a normal GH axis, neuroDrd2KO mice displayed fewer somatotropes; reduced hypothalamic Ghrh expression, pituitary GH content, and serum IGF-I levels; and exhibited reduced body size and weight. As a consequence of a GH axis deficit, neuroDrd2KO adult males excreted low levels of major urinary proteins and their urine failed to promote aggression and territorial behavior in control male challengers, in contrast to the urine taken from control adult males. These findings reveal that central D2Rs mediate a neuroendocrine-exocrine cascade that controls the maturation of the GH axis and downstream signals that are critical for fitness, social dominance, and competition between adult males.

Placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women’s blood serum

The aim of this work is to evaluate levels of placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women's blood serum before, during and after delivery. Furthermore, the aim is to search for links and interdependence of GH1, PGH and IGF-I concentrations. Seventy nine blood samples were taken one to two hours before, during and half an hour after expulsion of placenta. All proteins studied were determined by ELISA method, using ELISA Kit. The highest PGH concentration and IGF-I concentration in pregnant women's blood serum was observed before delivery while GH1 concentration was lowest. During and after delivery PGH and IGF-I concentration decreased proportionately and pituitary growth hormone concentration increased accordingly. About half an hour after delivery of the placenta, GH1 concentration was highest. In pregnant women's blood there is a metabolic interdependence between PGH and IGF-I. Their concentration increases proportionately during pregnancy and decreases after delivery. It appears that labor and delivery releases GH1 blockade, which level rises three-fold during delivery. After parturition its role and concentration returns to levels before pregnancy.

Simulation of the apparent effects of mebanazine on growth hormone by pair-feeding of control animals.

Abstract The degree and duration of insulin hypoglycaemia was potentiated by chronic oral medication with mebanazine in rats. Hypophysectomy alone increased sensitivity to insulin but did not abolish the potentiating effect of mebanazine. Chronic mebanazine treatment (15 mg/kg/day) for 6 weeks markedly reduced weight gain, food and water consumption and pituitary growth hormone content, but the results were not significantly different from those in unmedicated pair-fed controls. Similarly, immature rats treated with mebanazine had a significant reduction in the width of the tibial epiphysial cartilage but this was not different from that in pair-fed animals. After 18 h of fasting, acute administration of mebanazine had little effect on food consumption in the 2 h period following dosing but a significant effect over 24 h. In fed rats mebanazine in a single oral dose significantly reduced eating in the following 6 h. Treatment with mebanazine at 2·5 mg/kg for 15 days significantly reduced food intake but did not potentiate insulin hypoglycaemia. From the results it would appear that previous suggestions that mebanazine specifically interferes with growth hormone release are incorrect and the findings emphasize the importance of measuring food intake in experiments of long duration.

PRL and GH synthesis and release from the sea bream ( Sparus auratus L.) pituitary gland in vitro in response to osmotic challenge

The endocrine factors prolactin (PRL) and growth hormone (GH) are believed to have counteracting effects in the adaption of fish to changes in environmental salinity. In order to further investigate this interaction sea bream were challenged with full seawater (SW) or freshwater (FW) for 7 days and the response of pituitary glands cultured in vitro to an osmotic challenge (230, 275 and 320 mOsm/kg) was assessed. In vitro PRL secretion from pituitaries of SW-adapted fish was unaltered in response to an osmotic challenge, while GH secretion increased in the lowest osmolality (230 mOsm/kg). In contrast, both GH and PRL secretion by pituitaries from FW challenged fish was significantly increased ( p < 0.01) over that of pituitaries from SW fish at the highest osmolality (320 mOsm/kg). After FW challenge pituitary PRL content and de novo synthesised and released PRL were significantly increased ( p < 0.01), while total PRL secretion was not different from SW animals. GH pituitary content decreased in FW animals while total secretion and secretion of de novo synthesised protein were significantly increased ( p < 0.01). In addition, after transfer of fish to FW expression of PRL and GH increased 3- and 2-fold, respectively. Despite the increase in PRL expression, no increase in total PRL secretion occurred and although in gills a 2-fold increase in the osmoregulatory marker, Na +/K +-ATPase activity was detected, profound haemodilution and a cumulative mortality of 40% occurred in sea bream placed in FW. Taken together the results suggest that the sea bream pituitary gland fails to respond appropriately to the osmotic challenge caused by low salinity and the physiological response evoked in vivo is not enough to allow this species to withstand and adapt to FW.

Effects of physical training on serum and pituitary growth hormone contents in diabetic rats

The present study investigated the effects of moderate physical training on some of the parameters in the GH-IGF axis in experimental diabetic rats. Male Wistar rats were allocated into the following groups: sedentary control, trained control, sedentary diabetic, trained diabetic. Diabetes was induced by alloxan (32 mg/kg, b.w. iv). The physical training protocol consisted of 1 h swimming session/day, 5 days/week for 8 weeks supporting a load corresponding to 90% of maximal lactate steady state. After the experimental period, blood was collected to measure serum glucose, insulin, triglycerides, albumin, insulin-like growth factors-I (IGF-I), and growth hormone (GH). Pituitary gland was removed for GH quantification. Diabetes increased blood glucose and triglycerides and decreased insulin, IGF-I, serum and pituitary GH. Physical training decreased glucose and triglycerides, and also counteracted the reduction of serum IGF-I in diabetic rats. In conclusion, physical training recovered serum IGF-I showing no alteration of serum or pituitary GH levels.

Duration and nature of altered pituitary function in the male rat after a single large dose of estrogen.

The effects of a single large dose (10 and 20 mg) of diethylstilbestrol dipropionate on the pituitary gland of the mature male rat were investigated at intervals up to 312 days. The initial rise in pituitary weight and serum radioimmunoassayable growth hormone and fall in pituitary growth hormone concentration were followed by gradual recovery to normal extending over 5 to 6 months. Testicular weight was diminished until day 136 and adrenal weight was raised until day 114. The early pituitary mitotic activity had subsided to normal by day 69. Pituitary prolactin concentrations as indicated by starch gel electrophoresis were raised on day 28. Enlarged pituitary glands during the period 69 to 140 days also contained increased prolactin concentrations. The individual variations among the rats killed during the latter period included greatly elevated serum growth hormone either with or without increased pituitary weight.

The Pregnancy‐Induced Increase in Baseline Circulating Growth Hormone in Rats is not Induced by Ghrelin

The elevation in baseline circulating growth hormone (GH) that occurs in pregnant rats is thought to arise from increased pituitary GH secretion, but the underlying mechanism remains unclear. Distribution, Fourier and algorithmic analyses confirmed that the pregnancy-induced increase in circulating GH in 3-week pregnant rats was due to a 13-fold increase in baseline circulating GH (P < 0.01), without any significant alteration in the parameters of episodic secretion. Electron microscopy revealed that pregnancy resulted in a reduction in the proportion of mammosomatotrophs (P < 0.01) and an increase in type II lactotrophs (P < 0.05), without any significant change in the somatotroph population. However, the density of the secretory granules in somatotrophs from 3-week pregnant rats was reduced (P < 0.05), and their distribution markedly polarised; the granules being grouped nearest the vasculature. Pituitary GH content was not increased, but steady-state GH mRNA levels declined progressively during pregnancy (P < 0.05). In situ hybridisation revealed that pregnancy was accompanied by a suppression of GH-releasing hormone mRNA expression in the arcuate nuclei (P < 0.05) and enhanced somatostatin mRNA expression in the periventricular nuclei (P < 0.05), an expression pattern normally associated with increased GH feedback. Although gastric ghrelin mRNA expression was elevated by 50% in 3-week pregnant rats (P < 0.01), circulating ghrelin, GH-secretagogue receptor mRNA expression and the GH response to a bolus i.v. injection of exogenous ghrelin were all largely unaffected during pregnancy. Although trace amounts of 'pituitary' GH could be detected in the placenta with radioimmunoassay, significant GH-immunoreactivity could not be observed by immunohistochemistry, indicating that rat placenta itself does not produce 'pituitary' GH. Although not excluding the possibility that the pregnancy-associated elevation in baseline circulating GH could arise from alternative extra-pituitary sources (e.g. the ovary), our data indicate that this phenomenon is most likely to result from a direct alteration of somatotroph function.

Vitamin A deficiency does not influence longitudinal growth in mice

Objective Growth hormone (GH) stimulates longitudinal growth, directly and indirectly, through the mediation of circulating and locally produced insulin-like growth factor 1 (IGF-1). The exact role of individual vitamins in modulating GH secretion or action, and somatic growth in general, is still not completely understood. It has been suggested that vitamin A (VA) and its physiologic active metabolite retinoic acid influence longitudinal growth by promoting the differentiation of pituitary cells toward GH-secreting cells and by stimulating secretion of GH. Accordingly, epidemiologic studies have shown that short children have lower VA intake than do children with normal stature. Methods To determine whether VA deficiency causes impairment of GH secretion, we have investigated the effect of a severely VA-deficient diet on growth in mice. Ten male mice born from mothers fed with VA-deficient diet since conception were maintained on a VA-deficient diet until the end of week 8 of life. Ten male mice born from mothers fed with a VA-sufficient diet and receiving a normal diet after weaning served as the control group. At the end of the study, we measured animals’ weight and length, body composition, tibia and femur lengths, liver retinol and retinyl esters storages, serum IGF-1, serum thyroxine, serum GH, and pituitary GH mRNA levels. Results Despite evidence of significant VA deficiency, we observed no effect on longitudinal growth or changes in pituitary GH mRNA, serum thyroxine, serum GH, or serum IGF-1 levels. Conclusion VA deficiency does not negatively affect longitudinal growth and pituitary GH content and action in mice.

Isolation of Atlantic halibut pituitary hormones by continuous-elution electrophoresis followed by fingerprint identification, and assessment of growth hormone content during larval development

Continuous-elution electrophoresis (CEE) has been applied to separate putative hormones from adult Atlantic halibut pituitaries. Soluble proteins were separated by size and charge on Model 491 Prep Cell (Bio-Rad), where the homogenate runs through a cylindrical gel, and protein fractions are collected as they elute from the matrix. Protein fractions were assessed by SDS–PAGE and found to contain purified proteins of molecular size from 10 to 33 kDa. Fractions containing proteins with molecular weights of approximately 21, 24, 28 and 32 kDa, were identified as putative growth hormone (GH), prolactin, somatolactin and gonadotropins, respectively. These were analyzed further by mass spectrometry and identified with peptide mass protein fingerprinting. The CEE technique was used successfully for purification of halibut GH with a 5% yield, and appears generally well suited to purify species-specific proteins often needed for research in comparative endocrinology, including immunoassay work. Thus, the GH obtained was subsequently used as standards and iodination label in a homologous radioimmunoassay, applied to analyze GH content through larval development in normally and abnormally metamorphosing larvae. As GH is mainly found in the pituitary, GH contents were analyzed in tissue extracts from the heads only. The pituitary GH content increases proportionally to increased larval weight from first feeding to metamorphic climax. No difference in relative GH content was found between normal and abnormal larvae and it still remains to be established if GH has a direct role in metamorphosis.

Iodine Deficiency Mitigates Growth Retardation and Osteopenia in Selenium-Deficient Rats

Selenium deficiency is associated with impaired bone metabolism and osteopenia in rats. However, it is not known how combined selenium and iodine deficiency affects bone metabolism. Therefore, we investigated the effect of selenium and iodine deficiency on bone metabolism in 2nd-generation selenium- and iodine-deficient rats. Selenium-deficient (Se-), iodine-deficient (I-), selenium- and iodine-deficient (Se-/I-), and control rats (Se+/I+), were pair-fed their respective diets until they were 74 d old. Each pair-fed rat was fed a selenium-adequate diet in the same amount as that consumed the day before by its selenium-deficient counterpart, taking food spillage into account. The skeletal phenotype was analyzed by dual energy X-ray absorptiometry, histomorphometry, and bone metabolism markers. Erythrocyte glutathione peroxidase activity (Gpx) and plasma thyroid hormones were measured to assess selenium and iodine status, respectively. In both Se-/I+ and Se-/I- rats, Gpx was reduced by 99% compared with pair-fed Se+/I+ and Se+/I- rats (P < 0.001). Iodine deficiency reduced plasma thyroxine by 64% in the 2 iodine-deficient groups (P < 0.001). Body weight, tail length, plasma insulin-like growth factor, pituitary growth hormone concentration, and femur and tibia bone mineral density were significantly greater in the Se-/I- rats than in the Se-/I+ rats. This study shows that iodine deficiency mitigated growth retardation and osteopenia in 2nd-generation selenium-deficient rats and suggests that adequate selenium status should be ensured before measures are taken to correct iodine deficiency.

Revealing the large-scale network organization of growth hormone-secreting cells

Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues.

Effects of domestication on growth physiology and endocrinology of Atlantic salmon (Salmo salar)

Selection programs for fish frequently target growth rate as a breeding goal, yet surprisingly little is known about which mechanisms underlying the growth process are being targeted. The aim of this study was thus to examine whether the process of artificial selection of Atlantic salmon (Salmo salar) that has resulted in higher growth rate resulted in underlying changes in the growth hormone (GH) – insulin-like growth factor I (IGF-I) axis of endocrine growth regulation. This was tested by comparing similarly reared seventh-generation farm salmon with wild salmon from the principal founder population of the farm strain at three life stages. Not unexpectedly, the domesticated fish outgrew their wild counterparts; this was most evident in salt water, where they averaged three times the weight by the end. Pituitary GH content was positively correlated with growth rate and correspondingly was significantly higher in the faster growing domesticated fish than in the wild fish. Plasma GH levels were also significantly higher in the domesticated fish, whereas IGF-I levels did not differ. These findings provide some of the first direct evidence indicating a link between domestication selection for growth and its endocrine regulation, whereby individuals with more active endocrine growth regulatory components are targeted.

Rat ghrelin stimulates growth hormone and prolactin release in the tilapia, Oreochromis mossambicus.

Recently, ghrelin (Ghr), a new peptide which specifically stimulates growth hormone (GH) release from the pituitary, was identified in the rat and human stomach. Ghrelin has been shown to stimulate GH release by acting through a growth hormone secretagogue (GHS) receptor in the rat. The present study describes the in vitro effect of rat Ghr on the release of GH and two forms of prolactin (PRL(177) and PRL(188)) in the tilapia, Oreochromis mossambicus. Rat Ghr stimulated the release of GH in a dose-related manner after 8 and 24 hr of incubation. Rat Ghr also significantly stimulated the release of PRL(177) and PRL(188) in a dose-related manner after 24 hr. Rat Ghr had no effect on the pituitary content of GH or PRL(188), but significantly increased PRL(177) content. These results show for the first time that rat Ghr significantly stimulates GH and PRL release in teleosts, and suggest that Ghr and a GHS receptor are present in fish.