scholarly journals Sex differences in somatotrope response to fasting: biphasic responses in male mice

2020 ◽  
Vol 247 (3) ◽  
pp. 213-224
Author(s):  
Tiffany K Miles ◽  
Ana Rita Silva Moreira ◽  
Melody L Allensworth-James ◽  
Angela K Odle ◽  
Anessa C Haney ◽  
...  
Keyword(s):  
Sex Differences ◽  
Serum Glucose ◽  
Significant Rise ◽  
Male Mice ◽  
Prolonged Fasting ◽  
Ghrelin Receptor ◽  
Gh Secretion ◽  
Serum Ghrelin ◽  
Serum Gh ◽  
Biphasic Responses

Anterior pituitary somatotropes are important metabolic sensors responding to leptin by secreting growth hormone (GH). However, reduced leptin signals caused by fasting have not always correlated with reduced serum GH. Reports show that fasting may stimulate or reduce GH secretion, depending on the species. Mechanisms underlying these distinct somatotrope responses to fasting remain unknown. To define the somatotrope response to decreased leptin signaling we examined markers of somatotrope function over different time periods of fasting. Male mice were fasted for 24 and 48 h, with female mice fasted for 24 h compared to fed controls ad libitum. Body weight and serum glucose were reduced in both males and females, but, unexpectedly, serum leptin was reduced only in males. Furthermore, in males, serum GH levels showed a biphasic response with significant reductions at 24 h followed by a significant rise at 48 h, which coincided with the rise in serum ghrelin levels. In contrast, females showed an increase in serum GH at 24 h. We then explored mechanisms underlying the differential somatotrope responses seen in males and observed that pituitary levels of Gh mRNA increased, with no distinction between acute and prolonged fasting. By contrast, the Ghrhr mRNA (encoding GH releasing hormone receptor) and the Ghsr mRNA (encoding the ghrelin receptor) were both greatly increased at prolonged fasting times coincident with increased serum GH. These findings show sex differences in the somatotrope and adipocyte responses to fasting and support an adaptive role for somatotropes in males in response to multiple metabolic signals.

scholarly journals Ghrelin drives GH secretion during fasting in man

2002 ◽  
pp. 203-207 ◽  
Author(s):  
AF Muller ◽  
SW Lamberts ◽  
JA Janssen ◽  
LJ Hofland ◽  
PV Koetsveld ◽  
...  
Keyword(s):  
Rapid Development ◽  
Elevated Serum ◽  
Endogenous Ligand ◽  
Double Blind ◽  
Fed State ◽  
Gh Secretion ◽  
Gh Receptor ◽  
Serum Ghrelin ◽  
Serum Gh ◽  
Stimulation Of

OBJECTIVES: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue receptor and is synthesized in the stomach. As ghrelin administration in man stimulates GH release, while serum ghrelin concentrations are elevated during fasting in man, this increase in ghrelin levels might be another mechanism whereby fasting results in stimulation of GH release. DESIGN AND SUBJECTS: In ten healthy non-obese males we performed a double-blind placebo-controlled crossover study comparing fasting with and fasting without GH receptor blockade. GH, ghrelin, insulin, glucose and free fatty acids were assessed. RESULTS: While ghrelin levels do not vary considerably in the fed state, fasting rapidly induced a diurnal rhythm in ghrelin concentrations. These changes in serum ghrelin concentrations during fasting were followed by similar, profound changes in serum GH levels. The rapid development of a diurnal ghrelin rhythm could not be explained by changes in insulin, glucose, or free fatty acid levels. Compared with fasting without pegvisomant, fasting with pegvisomant did not change the ghrelin rhythm. CONCLUSIONS: These data indicate that ghrelin is the main driving force behind the enhanced GH secretion during fasting.

EFFECT OF l-DOPA ADMINISTRATION ON GROWTH HORMONE SECRETION IN NORMAL SUBJECTS AND PARKINSONIAN PATIENTS

1972 ◽  
Vol 54 (3) ◽  
pp. 425-433 ◽  
Author(s):  
F. CAVAGNINI ◽  
M. PERACCHI ◽  
G. SCOTTI ◽  
U. RAGGI ◽  
A. E. PONTIROLI ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Normal Subjects ◽  
Significant Rise ◽  
Arginine Infusion ◽  
Physiological Regulation ◽  
Gh Secretion ◽  
Before And After ◽  
Serum Gh

SUMMARY The effect of both oral and intravenous administration of l-DOPA on growth hormone (GH) secretion was studied in a group of normal volunteers: a significant rise of serum GH levels was observed in both cases. Growth hormone release in response to insulin hypoglycaemia and to arginine infusion was evaluated in a group of Parkinsonian patients before and after 25 days' treatment with l-DOPA plus a DOPA-decarboxylase inhibitor. In addition, GH response to the above stimuli was studied in a group of patients who had been under treatment for more than 6 months with l-DOPA alone. In untreated Parkinsonian patients, GH response to insulin hypoglycaemia was at the lower limit of normal range while arginine-induced GH release was significantly reduced. Treatment with l-DOPA did not increase GH responses. Some possible interpretations of the results are discussed. The findings support the possibility that dopamine plays a role in the physiological regulation of GH secretion, as in the case of luteinizing hormone, follicle-stimulating hormone and prolactin release.

scholarly journals Development-Dependent Plasticity in Vasoactive Intestinal Polypeptide Neurons in the Infralimbic Cortex

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Stuart A Collins ◽  
Ipe Ninan
Keyword(s):  
Sex Differences ◽  
Anxiety Disorders ◽  
Vasoactive Intestinal Polypeptide ◽  
Cortical Plasticity ◽  
Male Mice ◽  
Infralimbic Cortex ◽  
Membrane Excitability ◽  
Gabaergic Transmission ◽  
Intestinal Polypeptide

Abstract The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.

scholarly journals Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1430-1442 ◽  
Author(s):  
Nicole H. Rogers ◽  
Heidi Walsh ◽  
Oscar Alvarez-Garcia ◽  
Seongjoon Park ◽  
Bruce Gaylinn ◽  
...  
Keyword(s):  
Food Intake ◽  
Caloric Restriction ◽  
Liver Steatosis ◽  
Severe Hypoglycemia ◽  
Metabolic Flexibility ◽  
Male Mice ◽  
Ambulatory Activity ◽  
Ghrelin Receptor ◽  
Liver Gene ◽  
Acyl Ghrelin

Abstract Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin−/−) or ghrelin receptor (Ghsr−/−), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin−/− and Ghsr−/− mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr−/− mice. CR of WT, Ghsr−/−, and Ghrelin−/− mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Pparγ expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling.

scholarly journals Ghrelin Receptor (GHS-R1a) and Its Constitutive Activity in Somatotroph Adenomas: A New Co-targeting Therapy Using GHS-R1a Inverse Agonists and Somatostatin Analogs

2014 ◽  
Vol 99 (12) ◽  
pp. E2463-E2471 ◽  
Author(s):  
Yves Mear ◽  
Marie-Pierre Blanchard ◽  
Céline Defilles ◽  
Thierry Brue ◽  
Dominique Figarella-Branger ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Inverse Agonist ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Constitutive Activity ◽  
Targeting Therapy ◽  
Ghrelin Receptor ◽  
Gh Secretion

Context: The ghrelin receptor GHS-R1a is highly expressed in human somatotroph adenomas and exhibits unusually high basal signaling activity. In humans, the suppression of this constitutive activity by mutation induces a short stature. Objective: Using a GHS-R1a inverse agonist, modified substance P (MSP), we explored the role of GHS-R1a constitutive activity in GH hypersecretion from somatotroph adenomas and as a putative therapeutic target. Design: The effects of MSP were assessed on GH secretion from 19 human somatotroph tumors in vitro. Moreover, these effects were compared with those of octreotide (somatostatin receptor subtype 2 [sst2] agonist) and with the combination of both drugs. Expression and localization of GHS-R1a and sst2 were studied. Results: For all tumors, MSP inhibited GH secretion in a dose-dependent manner from 13 to 64%. Moreover, MSP enhanced octreotide-induced GH inhibition. For five tumors, the effects of combined MSP plus octreotide treatment were significantly higher than the sum of effects of each drug alone. MSP increased the membrane localization of GHS-R1a and of microdomains colocalizing sst2-GHS-R1a, highlighting the cooperation between the two drugs. Conclusions: The GHS-R1a inverse agonist could open new therapeutic options for acromegalic patients, particularly patients partially sensitive to octreotide whose GH secretion is not completely controlled by the sst2 agonist.

scholarly journals Somatotropic responses to soy protein alone and as part of a meal.

2008 ◽  
Vol 159 (1) ◽  
pp. 15-18 ◽  
Author(s):  
Anneke J A H van Vught ◽  
Arie G Nieuwenhuizen ◽  
Robert-Jan M Brummer ◽  
Margriet S Westerterp-Plantenga
Keyword(s):  
Soy Protein ◽  
Dietary Fat ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Dietary Carbohydrates ◽  
Oral Ingestion ◽  
Gh Secretion ◽  
Important Regulator ◽  
Insulin Responses ◽  
Serum Gh

ContextGH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal.Objective/designWe compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19–26 kg/m2, 19–36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min.ResultsGH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05).ConclusionThe somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.

GROWTH HORMONE LEVELS IN NORMOGLYCEMIC AND HYPOGLYCEMIC INFANTS BORN SMALL FOR GESTATIONAL AGE

PEDIATRICS ◽  
1971 ◽  
Vol 48 (2) ◽  
pp. 190-199
Author(s):  
James R. Humbert ◽  
Ronald W. Gotlin
Keyword(s):  
Growth Hormone ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Gh Deficiency ◽  
Newborn Infants ◽  
Significant Rise ◽  
Glucose Levels ◽  
Appropriate For Gestational Age ◽  
A Prospective Study ◽  
Serum Gh

Recent investigations have raised the possibility that growth hormone (GH) influences intra-uterine weight and length. Moreover, the hypoglycemic tendency of small for gestational age (FSGA) infants and their small size could result from GH deficiency. To verify these hypotheses, a prospective study of daily serum GH and glucose levels was conducted in 46 newborn infants, including 18 FSCA infants, 18-full-term, appropriate for gestational age (FAGA), and 10 premature (PR) infants. Two FSGA babies became hypoglycemic. Both manifested normal GH competence as evidenced by normal daily GH levels, adequate GH response to arginine provocation, and satisfactory growth for over 2 years. Eleven of 12 FSGA babies followed from 14 to 26 months showed no evidence of impaired linear growth. The FSGA babies had GH values similar in magnitude and pattern to those of FAGA and PR infants. During the second half of the first postnatal day, a significant rise in serum GH occurred in all infants regardless of their size or gestational age; this rise may be the result of the stimulating effect of early milk feedings. GH deficiency does not appear to contribute to either the small size or hypoglycemic tendency of FSGA newborn infants.

Is there a place for urinary growth hormone measurement?

1993 ◽  
Vol 128 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Maria N Moreira-Andrés ◽  
Francisco J Cañizo ◽  
Federico Hawkins
Keyword(s):  
Growth Hormone ◽  
Screening Method ◽  
Small Sample ◽  
Point Of View ◽  
Intrasubject Variability ◽  
Gh Secretion ◽  
Lack Of Information ◽  
Low Levels ◽  
Plasma Gh ◽  
Serum Gh

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

The influence of insulin on circulating ghrelin

2003 ◽  
Vol 284 (2) ◽  
pp. E313-E316 ◽  
Author(s):  
Daniel E. Flanagan ◽  
Mark L. Evans ◽  
Teresa P. Monsod ◽  
Frances Rife ◽  
Rubina A. Heptulla ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Insulin Infusion ◽  
Significant Rise ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Physiological Regulator ◽  
Underlying Mechanisms ◽  
Mean Glucose

Ghrelin is a novel peptide that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus. It may function as a third physiological regulator of GH secretion, along with GH-releasing hormone and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis. Although feeding suppresses ghrelin production and fasting stimulates ghrelin release, the underlying mechanisms controlling this process remain unclear. The purpose of this study was to test the hypotheses, by use of a stepped hyperinsulinemic eu- hypo- hyperglycemic glucose clamp, that either hyperinsulinemia or hypoglycemia may influence ghrelin production. Having been stable in the period before the clamp, ghrelin levels rapidly fell in response to insulin infusion during euglycemia (baseline ghrelin 207 ± 12 vs. 169 ± 10 fmol/ml at t = 30 min, P < 0.001). Ghrelin remained suppressed during subsequent periods of hypoglycemia (mean glucose 53 ± 2 mg/dl) and hyperglycemia (mean glucose 163 ± 6 mg/dl). Despite suppression of ghrelin, GH showed a significant rise during hypoglycemia (baseline 4.1 ± 1.3 vs. 28.2 ± 3.9 μg/l at t = 120 min, P < 0.001). Our data suggest that insulin may suppress circulating ghrelin independently of glucose, although glucose may have an additional effect. We conclude that the GH response seen during hypoglycemia is not regulated by circulating ghrelin.

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