The growth hormone axis and cognition: empirical results and integrated theory derived from giant transgenic mice

1999 ◽  
Vol 77 (12) ◽  
pp. 1874-1890 ◽  
Author(s):  
C D Rollo ◽  
C V Ko ◽  
JG A Tyerman ◽  
L J Kajiura
Keyword(s):  
Growth Hormone ◽  
Accelerated Aging ◽  
Error Rates ◽  
Transgenic Rat ◽  
Brain Functioning ◽  
Neuroendocrine Mechanisms ◽  
System Functioning ◽  
Plasma Gh ◽  
Enhanced Learning

Sleep is required for the consolidation of memory for complex tasks, and elements of the growth-hormone (GH) axis may regulate sleep. The GH axis also up-regulates protein synthesis, which is required for memory consolidation. Transgenic rat GH mice (TRGHM) express plasma GH at levels 100-300 times normal and sleep 3.4 h longer (30%) than their normal siblings. Consequently, we hypothesized that they might show superior ability to learn a complex task (8-choice radial maze); 47% of the TRGHM learned the task before any normal mice. All 17 TRGHM learned the task, but 33% of the 18 normal mice learned little. TRGHM learned the task significantly faster than normal mice (p < 0.05) and made half as many errors in doing so, even when the normal nonlearners were excluded from the analysis. Whereas normal mice expressed a linear learning curve, TRGHM showed exponentially declining error rates. The contribution of the GH axis to cognition is conspicuously sparse in literature syntheses of knowledge concerning neuroendocrine mechanisms of learning and memory. This paper synthesizes the crucial role of major components of the GH axis in brain functioning into a holistic framework, integrating learning, sleep, free radicals, aging, and neurodegenerative diseases. TRGHM show both enhanced learning in youth and accelerated aging. Thus, they may provide a powerful new probe for use in gaining an understanding of aspects of central nervous system functioning, which is highly relevant to human health.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion

1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh ◽  
Hypophysial Portal

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

Diurnal Variations of Plasma Growth Hormone and Brain Monoamines in Adult Male Rats

1973 ◽  
Vol 51 (12) ◽  
pp. 890-892 ◽  
Author(s):  
R. Collu ◽  
J. C. Jéquier ◽  
J. Letarte ◽  
G. Leboeuf ◽  
J. R. Ducharme
Keyword(s):  
Growth Hormone ◽  
Adult Male ◽  
Physiological Role ◽  
Male Rats ◽  
Male Rat ◽  
Plasma Growth Hormone ◽  
Gh Secretion ◽  
Adult Male Rat ◽  
Plasma Gh

Brain levels of monoamines (MA) in the adult male rat show a diurnal pattern of secretion with noradrenaline (NA) and serotonin (5-HT) reaching a peak at 1300 and 1800, respectively, and dopamine (DA) showing a bimodal pattern with peaks at 0500 and 1800. Plasma growth hormone (GH) values fluctuate widely during the nycthemeral period. Statistically significant correlations between plasma GH and brain MA levels, confirming the existence of a physiological role of MA in the control of GH secretion, could not be demonstrated in the present study.

EFFECT OF VARIOUS ADRENERGIC RECEPTOR STIMULATING AND BLOCKING AGENTS ON HUMAN GROWTH HORMONE SECRETION

1972 ◽  
Vol 54 (2) ◽  
pp. 195-206 ◽  
Author(s):  
F. MASSARA ◽  
F. CAMANNI
Keyword(s):  
Growth Hormone ◽  
Adrenergic Receptor ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Human Growth ◽  
Plasma Growth Hormone ◽  
Alpha Adrenergic Receptors ◽  
Blocking Agents ◽  
Plasma Gh

SUMMARY The effects of various adrenergic substances, either alone or in association with alpha and beta blocking agents, on human plasma growth hormone (GH) were studied in 36 normal volunteers. Plasma GH levels were unaffected by i.v. adrenaline (10 μg/min for 30 min) or by propranolol (1·5 mg/min for 10 min). Given together at the same doses, these drugs provoked sharp increases in plasma GH (from 8·5 to > 100 ng/ml; a mean increase of 30±8·02 (s.e.m.)). Reduction of the adrenaline dose to 7 μg/min produced a positive response in four out of six cases. The GH response to propranolol plus adrenaline was suppressed by simultaneous administration of phentolamine, but not significantly altered by glucose and aminophylline. Noradrenaline (7–14 μg/min for 30 min) produced no changes in plasma GH levels in six cases, while its association with propranolol was followed by an increase in only one out of four cases. Phenylephrine and tyramine were without effect, with or without propranolol. In five out of six cases, GH values gradually increased after oral administration of 1 g l-DOPA (from 4·2 to 85 ng/ml; mean, 30·2). This response was totally suppressed by phentolamine. It is considered that stimulation of GH by propranolol plus adrenaline and l-DOPA is mediated by alpha-adrenergic receptors. The possible role of a beta-inhibiting effect is discussed.

scholarly journals Melatonin Stimulates the Release of Growth Hormone and Prolactin by a Possible Induction of the Expression of Frog Growth Hormone-Releasing Peptide and Its Related Peptide-2 in the Amphibian Hypothalamus

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 962-970 ◽  
Author(s):  
Vishwajit S. Chowdhury ◽  
Kazutoshi Yamamoto ◽  
Izumi Saeki ◽  
Itaru Hasunuma ◽  
Taichi Shimura ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Median Eminence ◽  
Physiological Role ◽  
Receptor Subtype ◽  
Melatonin Receptor ◽  
Melatonin Secretion ◽  
Melatonin Administration ◽  
Plasma Gh ◽  
Precursor Mrna

We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN) and median eminence, respectively. To understand the physiological role of fGRP and fGRP-RP-2, we investigated the mechanisms that regulate the expression of these neuropeptides. This study shows that melatonin induces the expression of fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of mature fGRP and fGRP-RPs in the diencephalon including the SCN and median eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased dose-dependently their expressions. The expression of fGRP precursor mRNA was photoperiodically controlled and increased under short-day photoperiods, when the nocturnal duration of melatonin secretion increases. To clarify the mode of melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated the expression of Mel1b, a melatonin receptor subtype, in SCN neurons expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL concentrations, whereas melatonin administration increased these hormone levels. These results suggest that melatonin induces the expression of fGRP and fGRP-RP-2, thus stimulating the release of GH and PRL in bullfrogs.

scholarly journals Role of Growth Hormone in Ghrelin’s Metabolic Actions

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A553-A553
Author(s):  
Deepali Gupta ◽  
Salil Varshney ◽  
Kripa Shankar ◽  
Sherri Osborne-Lawrence ◽  
Nathan P Metzger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Blood Glucose ◽  
Food Intake ◽  
Calorie Restriction ◽  
Gh Secretion ◽  
Gh Cells ◽  
Life Threatening ◽  
Plasma Gh

Abstract Objective: Ghrelin regulates eating, body weight, and blood glucose. Upon binding to its receptor (growth hormone secretagogue receptor; GHSR), administered ghrelin increases food intake, body weight, and blood glucose. In contrast, blocking ghrelin lowers body weight and food intake. Also, mice that lack ghrelin or GHSR develop life-threatening hypoglycemia when submitted to a prolonged caloric restriction protocol providing only 40% of usual daily calories. Although GHSR was first identified in the pituitary, ghrelin was first defined by its ability to stimulate GH secretion via GHSRs, GH replacement prevents hypoglycemia in ghrelin-KO mice undergoing prolonged caloric restriction, and GH is known to modulate body composition, relatively little attention has been devoted to the role of GH-secreting pituitary somatotrophs (“GH cells”) in ghrelin action. The objective here was to determine the requirement for GHSR-expressing GH cells in mediating ghrelin’s metabolic actions. Methods: Mice with GH cell-selective GHSR deletion were generated by crossing novel GH-IRES-Cre mice to novel floxed-GHSR mice. GH cell-selective GHSR knockout mice and three control littermate groups were studied. Plasma GH, food intake, and blood glucose were measured after ip or sc ghrelin administration. Blood glucose and plasma GH were measured over the course of a 15-d calorie restriction protocol providing only 40% of usual daily calories. Results: In mice with GH cell-selective GHSR deletion, ghrelin-induced GH secretion and food intake were attenuated (by 84.1% at 15 min and by 35.3% at 45 min, respectively) as compared to controls; ghrelin-induced blood glucose elevation was unchanged. Mice with GH cell-selective GHSR deletion exhibited an attenuated GH rise (by 76.8%) over the 15-d calorie restriction period, yet they nonetheless resisted life-threatening hypoglycemia which is observed in similarly-treated ghrelin-KO mice, GHSR-null mice, and mice with hepatocyte-selective GH receptor deletion. Conclusions: These results suggest that GH cell-expressed GHSRs are required for ghrelin’s acute orexigenic and GH secretory actions but are dispensable for ghrelin’s glucoregulatory actions, at least in the settings assessed here. Although GH cell-expressed GHSRs are required for the progressive GH elevations associated with prolonged calorie restriction, they are not required for ghrelin’s overall protective effects to block prolonged calorie restriction-associated hypoglycemia.

scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

scholarly journals The Role of Neuropeptide Y in the Nucleus Accumbens

2021 ◽  
Vol 22 (14) ◽  
pp. 7287
Author(s):  
Masaki Tanaka ◽  
Shunji Yamada ◽  
Yoshihisa Watanabe
Keyword(s):  
Nervous System ◽  
Nucleus Accumbens ◽  
Neuropeptide Y ◽  
Emotional Behavior ◽  
Characteristic Functions ◽  
Receptor Subtypes ◽  
Neuroendocrine Mechanisms ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

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