Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe

Henry, Belinda A.; Rao, Arathi; Tilbrook, Alan John; Clarke, Iain J.

doi:10.1677/joe.0.170r001

Cited by 45 publications

(44 citation statements)

References 38 publications

(44 reference statements)

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“…Fasting has been shown to suppress HPT SST mRNA in male mice and ewes (21,29,46), consistent with the current observations showing an overall reduction in HPT SST mRNA, which reached significance in females (Fig. 3A).…”

Section: Resultssupporting

confidence: 92%

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Córdoba-Chacón

Gahete

Castaño

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Córdoba-Chacón J, Gahete MD, Castaño JP, Kineman RD, Luque RM. Somatostatin and its receptors contribute in a tissuespecific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice. Am J Physiol Endocrinol Metab 300: E46 -E54, 2011. First published October 13, 2010; doi:10.1152/ajpendo.00514.2010.-Somatostatin (SST) inhibits growth hormone (GH) secretion and regulates multiple processes by signaling through its receptors sst1-5. Differential expression of SST/ssts may contribute to sex-specific GH pattern and fastinginduced GH rise. To further delineate the tissue-specific roles of SST and sst1-5 in these processes, their expression patterns were evaluated in hypothalamus, pituitary, and stomach of male and female mice under fed/fasted conditions in the presence (wild type) or absence (SST-knockout) of endogenous SST. Under fed conditions, hypothalamic/stomach SST/ssts expression did not differ between sexes, whereas male pituitary expressed more SST and sst2A/2B/3/5A/ 5TMD2/5TMD1 and less sst1, and male pituitary cell cultures were more responsive to SST inhibitory actions on GH release compared with females. This suggests that local pituitary SST/ssts can contribute to the sexually dimorphic pattern of GH release. Fasting (48 h) reduced stomach sst2A/B and hypothalamic SST/sst2A expression in both sexes, whereas it caused a generalized downregulation of pituitary sst subtypes in male and of sst2A only in females. Thus, fasting can reduce SST sensitivity across tissues and SST input to the pituitary, thereby jointly contributing to enhance GH release. In SST-knockout mice, lack of SST differentially altered sst subtype expression levels in both sexes, supporting an important role for SST in sex-dependent control of GH axis. Evaluation of SST, IGF-I, and glucocorticoid effects on hypothalamic and pituitary cell cultures revealed that these hormones could directly account for alterations in sst2/5 expression in the physiological states examined. Taken together, these results indicate that changes in SST output and sensitivity can contribute critically to precisely define, in a tissue-dependent manner, the sex-specific metabolic regulation of the GH axis.

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Section: Resultssupporting

confidence: 92%

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Córdoba-Chacón

Gahete

Castaño

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…The fat ewes in our study had substantially higher circulating concentrations of leptin than the lean ewes and this is consistent with our previous studies using this model of dietary manipulation [45, 63]. It is well accepted that leptin is synthesized in adipocytes and inhibits appetite and plays a role in regulating energy expenditure [64, 65].…”

Section: Discussionsupporting

confidence: 91%

Responses of the Hypothalamopituitary Adrenal Axis and the Sympathoadrenal System to Isolation/Restraint Stress in Sheep of Different Adiposity

et al. 2008

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There is evidence that levels of adipose tissue can influence responses of the hypothalamopituitary-adrenal (HPA) axis to stress in humans and rats but this has not been explored in sheep. Also, little is known about the sympathoadrenal responses to stress in individuals with relatively different levels of adipose tissue. We tested the hypothesis that the stress-induced activation of the HPA axis and sympathoadrenal system is lower in ovariectomized ewes with low levels of body fat (lean) than ovariectomized ewes with high levels of body fat (fat). Ewes underwent dietary manipulation for 3 months to yield a group of lean ewes (n = 7) with a mean (±SEM) live weight of 39.1 ± 0.9 kg and body fat of 8.9 ± 0.6% and fat ewes (n = 7) with a mean (±SEM) live weight of 69.0 ± 1.8 kg and body fat of 31.7 ± 3.4%. Fat ewes also had higher circulating concentrations of leptin than lean ewes. Blood samples were collected every 15 min over 8 h when no stress was imposed (control day) and on a separate day when 4 h of isolation/restraint was imposed after 4 h of pretreatment sampling (stress day). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, epinephrine and norepinephrine did not change significantly over the control day and did not differ between lean and fat ewes. Stress did not affect plasma leptin levels. All stress hormones increased significantly during isolation/restraint stress. The ACTH, cortisol and epinephrine responses were greater in fat ewes than lean ewes but norepinephrine responses were similar. Our results suggest that relative levels of adipose tissue influence the stress-induced activity of the hypothalamopituitary-adrenal axis and some aspects of the sympathoadrenal system with fat animals having higher responses than lean animals.

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“…Taken together, these results suggest that there are both positive and negative regulators of GHRH expression in the fasted state, where under certain physiologic conditions the balance between these regulators can be skewed to favor GHRH synthesis. This logic is supported by the report of Henry et al (2001), who observed that food restriction in the ovariectomized ewe, which increases NPY mRNA (McShane et al 1993), also increased GHRH mRNA.…”

Section: Seungjoon Park and Others · Effects Of Fasting On The Gh-axisupporting

confidence: 62%

Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat

Park

Sohn²,

Kineman³

2004

Journal of Endocrinology

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Fasting results in a reciprocal shift in hypothalamic neuropeptide Y (NPY) and GH-releasing hormone (GHRH) expression in the adult male rat. It is hypothesized that the fasting-induced rise in NPY is responsible for the GHRH decline and subsequent attenuation of pulsatile GH release. Fasting also leads to a decrease in circulating IGF-I, attributed to both reduced GH release and peripheral GH resistance. Although pituitary GH output is suppressed in the fasted rat, we report herein that pituitary GHRH receptor (GHRH-R) and GH secretagogue receptor (GHS-R) mRNA levels are increased, while pituitary expression of the somatostatin receptor subtype 2 (sst2) and 5 (sst5) is decreased, as determined by real-time reverse transcription (RT)-PCR. A shift in the expression of pituitary receptor subtypes to favor GH synthesis and release may be due, at least in part, to a decline in GH/IGF-I negative feedback. In order to test this hypothesis, we compared hypothalamic and pituitary response to fasting (72 h) in normal male rats and rats with isolated GH deficiency (spontaneous dwarf rats (SDR)). Circulating GH levels were undetectable in SDR, and IGF-I levels were less than 10% of normal controls. Fasting stimulated NPY mRNA levels in SDR; however, the rise in NPY mRNA levels was not accompanied by a fall in GHRH mRNA, as observed in fasted normal rats. In fact, GHRH mRNA levels paradoxically rose in the fasted SDR to 135% of fed controls. At the pituitary level, fasting did not alter sst2 and sst5 mRNA levels in SDR but did stimulate the expression of GHRH-R and GHS-R to 165% and 149% of fed controls, respectively. These results demonstrate that the fasting-induced changes in pituitary expression of sst2 and sst5, but not GHRH-R and GHS-R, are GH/IGF-I dependent. In addition, these results argue against the theory that the negative association of NPY and GHRH expression observed following fasting represents a simple cause-and-effect relationship and suggest that GH, either directly or indirectly, mediates the effects of fasting on hypothalamic GHRH expression.

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Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe

Cited by 45 publications

References 38 publications

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

Responses of the Hypothalamopituitary Adrenal Axis and the Sympathoadrenal System to Isolation/Restraint Stress in Sheep of Different Adiposity

Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat

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