Circulating Growth Hormone Levels Research Articles

Oral contraception enhances growth hormone responsiveness to hyper‐ and hypoglycaemia

Plasma glucose levels influence growth hormone concentrations. Oral contraceptives are known to affect circulating growth hormone levels and glucose metabolism. While growth hormone plays an important role in hypoglycaemia counter-regulation, it has been shown that oral contraceptives increase growth hormone concentrations. In this context, we tested if serum growth hormone concentrations display a differential response on glycaemic variations in healthy women using oral contraceptives and those not using contraceptives. Fifteen healthy women with oral contraceptive treatment and 10 without participated in a stepwise hyper- and hypoglycaemic glucose clamp procedure. Serum growth hormone concentrations were measured at euglycaemic baseline and subsequently at plasma glucose plateaus of 8.8, 6.8, 4.8 and 2.8 mmol/l. Growth hormone values were significantly higher in women using oral contraceptives throughout the experiments (P = 0.001). Hyperglycaemia decreased growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those who were not using oral contraceptives (P = 0.241). Hypoglycaemia significantly elevated growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those not using oral contraceptives (P = 0.094). Maximum growth hormone values were reached at the end of the hypoglycaemic plateau, with significantly higher concentrations in the group using oral contraceptives than in the group not using oral contraceptives (P = 0.016). Healthy women on oral contraceptive treatment display an increased responsiveness of growth hormone to hypoglycaemic, as well as hyperglycaemic conditions and generally higher serum growth hormone concentrations than women without oral contraceptives. Given the known boosting effects of growth hormone on hypoglycaemic hormonal counter-regulation, oral contraceptives may thus be a pharmacological candidate contributing to combat hypoglycaemia unawareness in women with diabetes in the future.

How useful are serum IGF-I measurements for managing GH replacement therapy in adults and children?

The optimal dosing of growth hormone (GH) therapy is challenging due to high inter-individual variability in subcutaneous GH absorption and sensitivity to the drug. Optimal dosing would maximize patient gains in height, body composition, and metabolic outcomes while minimizing GH adverse events. The pulsatile secretion of GH, however, does not allow direct assessment of circulating GH levels as a measure of response to GH therapy. Insulin-like growth factor (IGF-I), a key marker of GH activity, has been shown to be useful in monitoring and adjusting GH dose during treatment of GH deficiency (GHD). Traditionally, monitoring IGF-I levels in response to GH therapy has been recommended for assessment of treatment compliance and safety. More recently, GH treatment guidelines have stated that IGF-I levels should also be used to guide GH dosing. This review examines whether individualized GH dosing based on the IGF-I response to GH therapy provides a better method for determining the GH replacement needs of pediatric and adult patients compared with conventional GH dosing, and whether IGF-I-based dosing improves outcomes such as height and body composition, with reduced side effects. Because IGF-I measurement presents its own difficulties, the current state of IGF-I assays is also discussed. The reviewed studies show that the use of GH dose adjustments based on IGF-I responses to GH therapy successfully reduces adverse events in adults with GHD and results in greater positive height attainment in children, without increasing adverse events. Long-term outcome studies are needed, as are internationally accepted guidelines for IGF-I measurement.

Ghrelin and growth hormone serum levels during the clonidine test in children with short stature and variable growth hormone status

The exact role of ghrelin in the control of growth hormone (GH) secretion has not been completely clarified as yet. The aim of the present study was 1) to investigate the effect of a substance promoting GH secretion (clonidine) on ghrelin levels in children with short stature with growth hormone deficiency (GHD) and normal growth hormone (NGH), and 2) to assess possible correlations between GH and ghrelin values during the clonidine test. Eighteen prepubertal children with short stature were included in the study. Using the results of two GH-provocative tests (glucagon and clonidine), the participants were divided into two groups: GHD and NGH. In both groups, ghrelin levels were determined during the clonidine stimulation test. Different responses regarding ghrelin levels during the clonidine stimulation test were observed in the two study groups (GHD and NGH). A decrease in ghrelin levels was observed in the NGH children accompanied by a rise in the circulating GH levels, whereas the GHD children demonstrated a rise in both ghrelin and GH levels. The data indicate an inverse relationship between circulating ghrelin and GH in NGH children, suggesting the presence of a negative feedback loop between ghrelin and GH. Analogous changes were not observed in GHD children.

Performance and thermoregulatory effects of chronic bupropion administration in the heat

The combination of acute dopamine/noradrenaline reuptake inhibition (bupropion; BUP) and heat stress (30 degrees C) significantly improves performance (9%). Furthermore the maintenance of a higher power output resulted in the attainment of significantly higher heart rates and rectal temperatures--above 40 degrees C--in the BUP trial compared to the placebo trial. Since BUP is an aid to cease smoking that is taken for longer periods, question remains if similar performance and thermoregulatory effects are found following administration of BUP over several days (10 days). The purpose of the present study was to examine the effects of chronic BUP on exercise performance, thermoregulation and hormonal variables in the heat. Eight trained male cyclists participated in the study. Subjects completed two trials consisting of 60 min fixed intensity exercise (55% W (max)) followed by a time trial (TT) in a double-blind randomized crossover design. Exercise was performed in 30 degrees C. Subjects took either placebo (PLAC) or BUP (Zyban) for 3 days (150 mg), followed by 300 mg for 7 days. Chronic BUP did not influence TT performance (BUP 40'42'' +/- 4'18''; PLAC 41'36'' +/- 5'12''), but significantly increased core temperature (P = 0.030). BUP significantly increased circulating growth hormone levels (PLAC: 9.8 +/- 5.8 ng L(-1); BUP: 13 +/- 6.8 ng L(-1); P < 0.008). Chronic BUP did not influence TT performance in 30 degrees C and subjects did not reach core temperature values as high as observed during the acute BUP study. It seems that chronic administration results in an adaptation of central neurotransmitter homeostasis, resulting in a different response to the drug.

Role of IGF-I in Type 2 diabetes: a focus on the mouse model

Insulin resistance, the key mechanism in Type 2 diabetes mellitus (T2DM) is also associated with the deregulation of other glucose homeostasis pathways, such as the growth hormone (GH)–IGF-I system. In this review, we summarize the endocrine and renal GH–IGF axis changes in db/db mice, a model of T2DM, and compare it with the nonobese diabetic mouse model of T1DM. In the latter, elevated circulating GH levels (associated with kidney disease) could be ameliorated with the use of GH antagonists. Contrary to that, in the obese db/db mice, serum GH and IGF-I levels are decreased and tissue levels of IGF-binding protein 1 (Igfbp1) are increased. The latter hinted again for the known inverse correlation between insulin and Igfbp1 and was mediated by changes in the transcription factor phosphorylated forkhead box O1 in obese animals. In addition, the decrease in circulating IGF-I and GH levels causes a state of low free and active IGF-I, which may further impair tissue viability (including pancreatic β-cells). Thus, further GH inhibition to modulate complications in T2DM is not indicated, but the therapeutic role of IGF-1 in this disease remains to be determined.

Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration†

Growth hormone controls many facets of a cell's biology through the transcription factors Stat5a and Stat5b (Stat5). However, whole body deletion of these genes from the mouse does not provide portentous information on cell-specific cytokine signaling. To explore liver-specific functions of Stat5, the entire Stat5 locus was deleted in hepatocytes using Cre-mediated recombination. Notably, Stat5-mutant mice developed fatty livers and displayed impaired proliferation of hepatocytes upon partial hepatectomy (PHx). Loss of Stat5 led to molecular consequences beyond the reduced expression of Stat5 target genes, such as those encoding suppressor of cytokine signaling 2 (SOCS2), Cish, and insulin-like growth factor 1 (IGF-1). In particular, circulating growth hormone levels were increased and correlated with insulin resistance and increased insulin levels. Aberrant growth hormone (GH)-induced activation of the transcription factors Stat1 and Stat3 was observed in mutant livers. To test whether some of the defects observed in liver-specific Stat5 deficient mice were due to aberrant Stat1 expression and activation, we generated Stat1(-/-) mice with a hepatocyte-specific deletion of Stat5. Concomitant loss of both Stat5 and Stat1 restored cell proliferation upon PHx but did not reverse fatty liver development. Thus the molecular underpinnings of some defects observed in the absence of Stat5 are the consequence of a deregulated activation of other signal transducers and activators of transcription (STAT) family members. Aberrant cytokine-Stat5 signaling in hepatocytes alters their physiology through increased activity of Stat1 and Stat3. Such cross-talk between different pathways could add to the complexity of syndromes observed in disease.

Skin in maturity: the endocrine and neuroendocrine pathways

Irrespective of age, most of the skin components are under the physiological control of endocrine and neuroendocrine factors. There is evidence that skin ageing appears complex showing much interindividual variability. Conceptually, ageing is a single biological process that is influenced and modulated by a series of various internal and exogenous factors. Among them, hormones and neuroendocrine signals play key roles in several ways. Ageing of most endocrine glands will in turn alter the skin biology. In addition, the age-related reduction in the intrinsic neuroendocrine activity of the skin will also alter the ageing rate of this organ. At last, various endocrinopathies will boost or conversely decrease the severity of the signs of cutaneous ageing.

Acyl Ghrelin and Metabolic Hormones in Pregnant and Lactating Sows

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor, is considered a pleiotropic regulator involved in a large array of functions, including control of energy balance, regulation of food intake and, more recently, modulation of the reproductive axis. The present study was aimed at determining the changes in plasma concentrations of acyl-ghrelin in pregnant and lactating sows, with special emphasis on the relationship with the levels of GH, leptin, non-esterified fatty acids (NEFA) and insulin-like growth factor (IGF-1). Blood samples were collected via jugular venipuncture from 22 multiparous sow 30, 60 and 90 days after artificial insemination, 7 and 21 days after farrowing and at first oestrus post-weaning. Plasma concentrations of acyl-ghrelin, leptin, GH and IGF-1 were quantified by validated radioimmunoassay; NEFA were determined using a colorimetric procedure. Plasma acyl ghrelin levels were highest at 30 days of pregnancy and decreased thereafter and during lactation. At the beginning of lactation, GH, IGF-1 and NEFA concentrations significantly increased, while a significant reduction occurred in leptin. In conclusion, ghrelin concentrations in sow maternal circulation does not seem to play an important role in maintaining circulating GH levels during lactation; moreover, ghrelin is not associated with leptin, NEFA and IGF-1 levels.

Growth Hormone Corrects Proliferation and Transcription of Phosphoenolpyruvate Carboxykinase in Livers of Old Mice via Elimination of CCAAT/Enhancer-binding Protein α-Brm Complex

Growth hormone (GH), which is reduced with age, corrects the impaired proliferative capacity of livers of old animals. In this paper, we present a mechanism by which GH eliminates age-dependent negative control of proliferation and increases transcription of liver-specific genes in livers of old mice. The reduced proliferative capacities of the liver of old animals are associated with the CCAAT/enhancer-binding protein alpha (C/EBPalpha)-Brm complex, which inhibits E2F-dependent promoters. We found that a sequestration of C/EBPalpha into complexes with Brm leads to a weak interaction of C/EBPalpha with promoters of liver-specific genes, expression of which is reduced in old animals. Injection of either GH or the regulator of the amplitude of endogenous GH release, ghrelin, reduces the C/EBPalpha-Brm complex in livers of old mice, leading to a derepression of E2F targets, to increased interactions of C/EBPalpha with promoters of liver-specific genes, and to correction of their expression. GH-dependent elimination of the complex is mediated by the inhibition of cyclin D3-CDK4 activity and by elevation of a phosphatase, protein phosphatase 2A, which dephosphorylates C/EBPalpha and dissociates the complex.

Recent advances in growth hormone signaling

Growth hormone (GH) is a major regulatory factor for overall body growth as evidenced by the height extremes in people with abnormal circulating GH levels or GH receptor (GHR) disruptions. GH also affects metabolism, cardiac and immune function, mental agility and aging. Currently, GH is being used therapeutically for a variety of clinical conditions including promotion of growth in short statured children, treatment of adults with GH deficiency and HIV-associated wasting. To help reveal previous unrecognized functions of GH, better understand the known functions of GH, and avoid adverse consequences that are often associated with exogenous GH administration, careful delineation of the molecular mechanisms whereby GH induces its diverse effects is needed. GH is a peptide hormone that is secreted into the circulation by the anterior pituitary and acts upon various target tissues expressing GHR. GH binding of GHR activates the tyrosine kinase Janus kinase 2 (JAK2), thus initiating a multitude of signaling cascades that result in a variety of biological responses including cellular proliferation, differentiation and migration, prevention of apoptosis, cytoskeletal reorganization and regulation of metabolic pathways. A number of signaling proteins and pathways activated by GH have been identified, including JAKs, signal transducers and activators of transcription (Stats), the mitogen activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3'-kinase (PI3K) pathway. Although these signal transduction pathways have been well characterized, the manner by which GH activates these pathways, the downstream signals induced by these pathways, and the cross-talk with other pathways are not completely understood. Recent findings have added vital information to our understanding of these downstream signals induced by GH and mechanisms that terminate GH signaling, and identified new GH signaling proteins and pathways. This review will highlight some of these findings, many of which are unexpected and some of which challenge previously held beliefs about the mechanisms of GH signaling.

Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice

Leptin-deficient obese mice (ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (approximately 1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.

A motilin agonist, erythromycin, decreases circulating growth hormone levels in normal subjects but not in diabetic subjects

Erythromycin (EM) is a common antibiotic known to be a specific agonist of motilin receptors. We have previously reported that administration of EM improves glycemic control in type 2 diabetes patients. In the present study, we tested the effect of EM on growth hormone (GH) secretion in normal and type 2 diabetic subjects. Erythromycin (300 mg) was administered orally in fasted type 2 diabetic ( n=12) and normal ( n=10) subjects. Blood samples were obtained before and 2 h after the administration. Blood glucose, plasma insulin, somatostatin (SS), and GH levels were determined. The same fasted groups received intravenous erythromycin infusion (10 mg/kg per hour) for 60 min. Blood samples were collected just prior to the infusion and at 15, 30, 45 and 60 min, and plasma GH and somatostatin levels during the infusion were determined. Oral EM administration increased insulin levels and decreased blood glucose levels. GH levels were significantly decreased, while SS levels did not change in normal subjects. In diabetic subjects, there was an increase in insulin levels, but no change in blood glucose, SS, and GH levels. Intravenous EM infusion resulted in a marked decrease in GH levels, while no change in SS levels occurred in normal subjects. There were no changes in SS and GH levels in diabetic subjects during the infusion. When diabetic subjects were divided into two groups with and without autonomic neuropathy, no changes in GH levels were seen in either group. We conclude that EM decreases GH levels in normal subjects while not changing SS levels. This effect was not observed in type 2 diabetic subjects.

Influence of circulating GH levels on GH-binding capacity measurements in the hepatic membrane of rainbow trout (Oncorhynchus mykiss): importance of normalization of results

In fish, regulation of the growth hormone (GH) receptor has been mainly analyzed by binding studies, with some discrepancies in the results. The present work aims at determining whether circulating GH levels influence the measurement of hepatic GH-binding capacities. To do this, the effectiveness of the dissociation of the GH/GH receptor (GHR) complex by an MgCl2 treatment was assessed in rainbow trout, and data on GH-binding capacities under various physiological conditions were studied using different means of expression. Our results reveal that MgCl2 treatment dissociated the liver GH/GHR complex formed under in vitro conditions (85 ± 23 vs. 361 ± 16 fmol/g of liver; p<0.001) but not in vivo, showing such treatment in trout is not applicable. A comparison of fasted (3 weeks) and fed fish revealed that GH-binding capacities, expressed as femtomoles per milligram protein or femtomoles per gram of liver, were similar in both fed and fasted fish. However, when changes in liver and body size were taken into account, the total GH-binding capacities were lower in the fasted fish (0.026 ± 0.006 vs. 0.062 ± 0.009 fmol/cm3 liver; p<0.05). One day after hypophysectomy or GH injection, changes in the plasma GH levels increased or decreased GH-binding capacities, respectively. Five days later, GH-binding capacities increased in GH-injected fish (527 ± 38 vs. 399 ± 38 fmol/g liver; p<0.01). Our interpretation is that acute treatment modified GH-binding capacities through receptor occupancy and that GH stimulated the synthesis of its own receptor. On the other hand, long-term treatment through successive injections of GH lowered the total binding capacities (approx. 40%), which could result from receptor occupancy. We conclude that circulating GH levels strongly influence the measurement of GH-binding capacities in the liver, thereby limiting interpretation of the binding data and preventing accurate conclusions to be drawn on GHR regulation.

Expression Analysis of Hypothalamic and Pituitary Components of the Growth Hormone Axis in Fasted and Streptozotocin-Treated Neuropeptide Y (NPY)-Intact (NPY+/+) and NPY-Knockout (NPY –/–) Mice

In the fasted and the streptozotocin (STZ)-induced diabetic male rat, hypothalamic growth hormone (GH)-releasing hormone (GHRH) mRNA levels, and pulsatile GH release are decreased. These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression. To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY^+/+) and NPY-knockout (NPY^–/–) mice by ribonuclease protection assay. In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR. Under fed conditions the GH axis of NPY^+/+ and NPY^–/– did not differ. In the NPY^+/+ mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA. These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2. In the NPY^–/– mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels. Fasting resulted in an overall increase in circulating GH, which reached significance in the fasted NPY^–/– mouse. Induction of diabetes in NPY^+/+ mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed. Induction of diabetes in NPY^+/+ and NPY^–/– mice, using a multiple, low-dose, STZ paradigm (5 consecutive daily injections of 40 mg/kg), did not alter body weight, hypothalamic neuropeptide expression or pituitary receptor expression, with the exception that sst2 mRNA levels were suppressed and GH levels did rise in the NPY^–/– mouse. These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA. In contrast to the rat, fasting clearly did not suppress circulating GH levels in mice, but resulted in an overall rise in mean GH levels, similar to that observed in other mammalian species. The fact that many of the fasting-induced changes in the GH axis were observed in the high-dose STZ-treated mice, but were not observed in the multiple, low-dose paradigm, suggests STZ-mediated modulation of GH axis function is dependent on the severity of the catabolic state and not hyperglycemia.

Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling

Resistance to growth hormone (GH) is a significant complication of advanced chronic renal failure. Thus while the circulating GH levels are normal or even elevated in uremia, resistance to the hormone leads to stunting of body growth in children and contributes to muscle wasting in adults. Insensitivity to GH is the consequence of multiple defects in the GH/insulin-like growth factor-1 (IGF-1) system. Expression of the GH receptor may be reduced, although this is not a consistent finding, GH activation of the Janus kinase 2-signal transducer (JAK2) and activator of transcription (STAT) signal transduction pathway is depressed and this leads to reduced IGF-1 expression, and finally there is resistance to IGF-1, a major mediator of GH action. We review these various defects with an emphasis on the GH-activated JAK2-STAT5 pathway, since this pathway is essential for normal body growth and there has been recent progress in our understanding of the perturbations that occur in uremia.

Relationship Between Growth and Plasma Concentrations of Ghrelin and Growth Hormone in Juvenile Beagle Dogs

Although the release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus, ghrelin also may be involved in GH release during juvenile period. We have examined plasma concentrations of acylated ghrelin, desacyl ghrelin, and GH in juvenile beagle dogs. Plasma acylated and desacyl ghrelin levels changed through aging; however, there was no closely correlation between ghrelin, body weight and circulating GH levels during juvenile period. The increase in body weight was essentially linear until 8 months of age, whereas plasma GH concentrations exhibited bimodal peaks for the meanwhile. The results suggest that ghrelin may not play internal cueing in GH secretion in juvenile beagle dogs.

Growth factors and muscle ageing

Loss of muscle mass (sarcopenia) is one of the main problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone (GH)/IGF-I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-I and that there are local as well as systemic forms of IGF-I which have different functions. At least two different kinds of IGF-I that are expressed by skeletal muscle are derived from the IGF-I gene by alternative splicing, one of which is expressed in response to physical activity which has now been called ‘mechano growth factor’ (MGF). The other is similar to the systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I required for upregulating protein synthesis. MGF differs from systemic IGF-IEa in that it has a different peptide sequence which is responsible for replenishing the satellite (stem) cells in skeletal muscle. The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels. GH treatment up regulates the level of IGF-I gene expression in older people and when combined with resistance exercise more is spliced towards MGF and hence should improve the ability of muscle to respond to physical activity. The possibility of ameliorating sarcopenia using MGF is discussed.

Growth hormone-releasing hormone neurons in the anestrus cat do not express progesterone receptors.

Ovarian steroids have been implicated in the regulation of growth hormone (GH) secretion in several species and increased progesterone secretion has been associated with elevated circulating GH levels in the cat. These high GH concentrations may be due, at least in part, to a direct action of progesterone on growth hormone-releasing hormone (GHRH) neurons. Using standard immunocytochemical methods coupled to high-temperature antigen retrieval, the objective of this study was to determine whether progesterone receptors were colocalized in GHRH neurons of the anestrus cat. GHRH perikarya were restricted to the infundibular nucleus and the ventral ventromedial nucleus and although frequently surrounded by numerous progesterone receptor-immunoreactive cells, none was colocalized. This study, therefore, provides evidence that, in the adult anestrus female cat, GHRH neurons do not express nuclear progesterone receptors.

Effects of pulsatile secretion of growth hormone (GH) on fat deposition in human GH transgenic rats

Growth hormone (GH) is an endocrine regulator of glucose and lipid metabolism as well as body growth. GH levels are decreased and a unique pulsatile secretory pattern becomes obvious after puberty particularly in males. Coincidentally with this, males tend to deposit body fat. Experimental and clinical evidence has accumulated that obesity is associated with a decrease in GH levels. A strain of transgenic rats has been generated with severe obesity but normal nose-to-tail length, which has low circulating GH levels without pulsatility (human growth hormone (hGH) transgenic rats). The present review mainly focuses on recent and current work analysing the relationship between the occurrence of obesity and low GH levels and/or the absence of GH pulsatility in this transgenic animal model. This model has elevated blood glucose, non-esterified fatty acid, insulin and leptin levels associated with hyperphagia, suggesting that these rats also carry insulin- and leptin-resistant characteristics. hGH transgenic rats were subjected to a pair-feeding treatment to normalize food intake and chronic GH replacement to normalize GH levels. While the pair-feeding for 8 weeks successfully suppressed body-weight gain, the fat pad : body weight ratio remained very similar to freely-eating control hGH transgenic rats, which indicates the hyperphagia is not the sole contributor to the excess fat accumulation in this model. However, continuous elevation of peripheral hGH levels (approximately 2-fold) for 8 weeks by means of a slow-release vehicle resulted in a significant decrease in the fat mass : body weight ratios by 30 %. This GH treatment altered neither food intake nor body-weight gain. Thus, two characteristic phenotypes observed in the hGH transgenic rats, hyperphagia and obesity, seem to be closely related to GH levels and GH secretory pattern. This relationship might be working in the regulation of changes in seasonal body composition in wild animals.

Effect of Fasting on Pituitary Growth Hormone Expression and Circulating Growth Hormone Levels in Striped Bass

Abstract The mechanisms controlling the circulating levels of growth hormone (GH) during periods of starvation in fish are not well defined. In this study, the effect of fasting on GH release and pituitary messenger RNA (mRNA) expression in striped bass Morone saxatilis was examined. Over a 4-week period, the body mass of striped bass fed to satiety increased 22.9%, while that of fasted fish decreased 17.3%. The plasma GH concentrations of fed fish remained low throughout the experiment, but those of fasted fish increased significantly (P < 0.001) after 2 and 4 weeks. The striped bass that were fasted for 2 weeks demonstrated a 33% increase (P = 0.10) in GH mRNA expression compared with those fed to satiety. These data confirm that short-term fasting in striped bass increases their circulating levels of GH in a manner similar to that experienced in other species of fish. This study also demonstrates—for the first time in a fish species—that pituitary GH mRNA expression increases during fasting, which sugg...