scholarly journals Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice

2020 ◽  
Vol 245 (2) ◽  
pp. 327-342 ◽  
Author(s):  
Harleen Kaur ◽  
Beverly S Muhlhausler ◽  
Pamela Su-Lin Sim ◽  
Amanda J Page ◽  
Hui Li ◽  
...  

Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4–13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.

2006 ◽  
Vol 189 (3) ◽  
pp. 655-664 ◽  
Author(s):  
Hnin ThidarMyint ◽  
Hiroko Yoshida ◽  
Tetsuya Ito ◽  
Hideto Kuwayama

The stimulatory effect of the novel gastric-derived hormone, ghrelin, on growth hormone (GH) secretion has been reported in domestic animals as well as in humans and rats. The octanoyl modification on the Ser3 residue of ghrelin appears to be essential for its endocrine activity. A major portion of circulatory ghrelin lacks acylation but possesses some biological activities other than GH stimulation; therefore, both types of acylated and des-acyl ghrelin are supposed to be important for energy homeostasis. The effects of pharmacological doses of rat and/or human ghrelin on GH secretion have been reported recently in ruminants; however, the physiological effect of exogenous bovine ghrelin on its own plasma level and on GH secretion is still unknown. Moreover, the RIA systems for the measurement of bovine active ghrelin and for bovine total ghrelin including acylated ghrelin, des-acyl ghrelin and all ghrelin peptides with an intact bovine C-terminal have not yet been validated. In this study, we established the RIA system for bovine ghrelin, and the dose-dependent effects of synthesized acylated bovine ghrelin(1–27) on plasma active and total ghrelin, GH, insulin and metabolites were measured in Holstein heifers. Six animals were intravenously injected with synthesized acylated bovine ghrelin (0, 0.1, 0.5, 1.0, 5.0, 10.0 μg/kg body weight (BW)) and plasma hormone concentrations were measured from serially collected samples. Bovine ghrelin RIA showed that the basal level of total ghrelin is approximately 16 times higher than that of active ghrelin in bovine plasma. Both forms of ghrelin were increased in a dose-dependent manner in response to bovine ghrelin injections, peak values were reached at 5 min after administration and returned to pre-injected values within 15 min. Plasma GH was responsive to all doses of bovine ghrelin in a dose-dependent manner, peaked as early as at 5–10 min after injection and returned to the basal value within 60 min. The GH area under curve 1 h after injection of the smallest dose of ghrelin used in this experiment (0.1 μg/kg BW) was significantly higher than that of the vehicle (0.1% BSA saline)-injected control group (P<0.05). The GH response to the highest dose of ghrelin (10.0 μg/kg BW) was greater than the response to 5.0 μg/kg BW ghrelin (P<0.001). Plasma glucose concentrations were not significantly altered by the administration of bovine ghrelin while plasma insulin levels were transiently stimulated by the higher doses of ghrelin (1.0, 5.0, 10.0 μg/kg BW). Plasma non-esterified fatty acid levels also increased following ghrelin administration. Our study indicates that a considerable quantity of both acylated and des-acyl ghrelin is circulating in the bloodstream, and also confirms that ghrelin is not only a potent stimulator of GH secretion but also plays a considerable role in energy homeostasis in Holstein heifers.


2020 ◽  
Vol 100 (4) ◽  
pp. 657-664
Author(s):  
Jiuxiu Ji ◽  
Taihua Jin ◽  
Rui Zhang ◽  
Angang Lou ◽  
Yingying Chen ◽  
...  

Yanbian yellow cattle breeding is limited by its slow growth. We previously found that the miRNA miR-6523a is differentially expressed between Yanbian yellow cattle and Han Yan cattle, which differ in growth characteristics. In this study, we evaluated the effects of miR-6523a on growth hormone (GH) secretion in pituitary cells of Yanbian yellow cattle. Bioinformatics analyses using TargetScan and RNAhybrid, as well as dual luciferase reporter assays, showed that miR-6523a targets the 3′ untranslated region of somatostatin receptor 5 (SSTR5). We further found that the mRNA and protein expression levels of GH in pituitary cells were significantly higher in cells treated with miR-6523a mimic than in the control group (P = 0.0082 and P = 0.0069). The GH mRNA and protein expression levels were lower in cells treated with miR-6523a inhibitor than in the control group, but the difference was not significant (P = 0.064 and P = 0.089). SSTR5 mRNA and protein levels were inhibited by miR-6523a mimic compared with the control group (P = 0.0024 and P = 0.0028) and were elevated slightly by miR-6523a inhibitor (P = 0.093 and P = 0.091). These results prove that miR-6523a regulates GH secretion in pituitary cells by SSTR5. More broadly, these findings provide a basis for studies of the roles of miRNAs in animal growth and development.


1987 ◽  
Vol 253 (1) ◽  
pp. E40-E44 ◽  
Author(s):  
P. J. Fielder ◽  
L. Ogren ◽  
D. Edwards ◽  
F. Talamantes

Hormonal and metabolic responses to fasting were studied in pregnant Swiss Webster mice. Food was removed from pregnant mice 12, 24, 36, or 48 h before death on day 12 or 15 of pregnancy. Serum mouse placental lactogen-II (mPL-II), mouse growth hormone (mGH), mouse prolactin (mPRL), free fatty acids (FFA), and glucose concentrations were determined for each group. In comparing fasted animals with fed controls, there was a significant increase in the serum mPL-II concentration after 24 and 48 h of fasting on day 12 and after 12, 36, and 48 h of fasting on day 15. Fasting significantly decreased the glucose and increased the FFA concentration of the serum at all fasting periods. Fasting had no effect on serum mPRL or mGH concentrations. In the second part of this study, pregnant mice were fasted for 24 h and then refed for an additional 24 h before being killed on day 12 of pregnancy. The changes in serum mPL-II, glucose, and FFA concentrations that occurred after a 24-h fast on day 12 of pregnancy were completely reversed by refeeding the animals for 24 h. Results from both studies indicate the involvement of mPL-II in the maternal response to fasting in pregnant mice.


2021 ◽  
Author(s):  
Anna Dons-Jensen ◽  
Sascha Siig Horup ◽  
Anne-Mette Hvas ◽  
Esben Thyssen Vestergaard ◽  
Rakel Fuglsang Johansen

Abstract Acyl ghrelin (AG) is the endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor and exogenous AG is a strong stimulator of GH secretion [1]. The role of endogenous AG has not yet been unraveled and its regulation is complex, but it is widely accepted that circulating levels of ghrelin correlate inversely with body mass index [2]. The peptide known as unacylated ghrelin (UAG) is both a precursor to AG and one of the split products, when AG is deacylated during its degradation, so increased turnover of AG results in higher levels of UAG [3].


Author(s):  
Hui Li ◽  
Georgia S Clarke ◽  
Stewart Christie ◽  
Sharon R Ladyman ◽  
Stephen J. Kentish ◽  
...  

Gastric vagal afferents (GVAs) sense food related mechanical stimuli and signal to the central nervous system, to integrate control of meal termination. Pregnancy is characterized by increased maternal food intake, which is essential for normal fetal growth and to maximize progeny survival and health. However, it is unknown whether GVA function is altered during pregnancy to promote food intake. This study aimed to determine the mechanosensitivity of GVAs and food intake during early-, mid-, and late- stages of pregnancy in mice. Pregnant mice consumed more food compared to non-pregnant mice, notably in the light phase during mid- and late pregnancy. The increased food intake was predominantly due to light phase increases in meal size across all stages of pregnancy. The sensitivity of GVA tension receptors to gastric distension was significantly attenuated in mid- and late pregnancy, while the sensitivity of GVA mucosal receptors to mucosal stroking was unchanged during pregnancy. To determine whether pregnancy associated hormonal changes drive these adaptations, the effects of estradiol, progesterone, prolactin and growth hormone, on GVA tension receptor mechanosensitivity were determined in non-pregnant female mice. The sensitivity of GVA tension receptors to gastric distension was augmented by estradiol, attenuated by growth hormone and unaffected by progesterone or prolactin. Together, the data indicate that the sensitivity of GVA tension receptors to tension is reduced during pregnancy, which may attenuate the perception of gastric fullness and explain increased food intake. Further, these adaptations may be driven by increases in maternal circulating growth hormone levels during pregnancy.


2017 ◽  
Vol 6 (4) ◽  
pp. 260-266 ◽  
Author(s):  
Kathryn L Gatford ◽  
Beverly S Muhlhausler ◽  
Lili Huang ◽  
Pamela Su-Lin Sim ◽  
Claire T Roberts ◽  
...  

Placenta-derived hormones including growth hormone (GH) in humans contribute to maternal adaptation to pregnancy, and intermittent maternal GH administration increases foetal growth in several species. Both patterns and abundance of circulating GH are important for its activity, but their changes during pregnancy have only been reported in humans and rats. The aim of the present study was to characterise circulating profiles and secretory characteristics of GH in non-pregnant female mice and throughout murine pregnancy. Circulating GH concentrations were measured in whole blood (2 μL) collected every 10 min for 6 h in non-pregnant diestrus female C57Bl/6J mice (n = 9), and pregnant females at day 8.5–9.5 (early pregnancy, n = 8), day 12.5–13.5 (mid-pregnancy, n = 7) and day 17.5 after mating (late pregnancy, n = 7). Kinetics and secretory patterns of GH secretion were determined by deconvolution analysis, while orderliness and regularity of serial GH concentrations were calculated by approximate entropy analysis. Circulating GH was pulsatile in all groups. Mean circulating GH and total and basal GH secretion rates increased markedly from early to mid-pregnancy, and then remained elevated. Pulse frequency and pulsatile GH secretion rate were similar between groups. The irregularity of GH pulses was higher in all pregnant groups than that in non-pregnant mice. Increased circulating GH in murine pregnancy is consistent with an important role for this hormone in maternal adaptation to pregnancy and placental development. The timing of increased basal secretion from mid-pregnancy, concurrent with the formation of the chorioallantoic placenta and initiation of maternal blood flow through it, suggests regulation of pituitary secretion by placenta-derived factors.


1974 ◽  
Vol 75 (3) ◽  
pp. 497-502
Author(s):  
Mayer B. Davidson ◽  
Roger M. Steele

ABSTRACT Since fructose is normally metabolized in diabetics and has recently been shown to stimulate GH secretion, it was used to assess GH responses in diabetics. Fourteen diabetics (9 on insulin) and 8 controls matched for weight were studied. Fructose, infused over 10 min, was compared to arginine, infused over 30 min, both at 0.5 g/kg. Samples were collected at 0, 30, 60, 90 and 120 min and GH responses assessed as area under the curve minus the fasting area. There was no significant difference between the GH responses in diabetics and controls to either agent. Responses to arginine and fructose were significantly correlated (r = 0.60, P < 0.01) in all subjects, but not related to therapy, duration of disease or fasting glucose (75–287 mg/100 ml) in the diabetics. Oral glucose blunted the GH response to fructose in 2 controls. It is concluded that 1) fructose can stimulate GH secretion in male diabetics; 2) however, fructose-stimulated GH responses are not increased in diabetes mellitus.


2021 ◽  
pp. 1-24
Author(s):  
Jan M. Wit ◽  
Sjoerd D. Joustra ◽  
Monique Losekoot ◽  
Hermine A. van Duyvenvoorde ◽  
Christiaan de Bruin

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of <i>GH1</i> or <i>GHSR</i>) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to <i>GH1</i> variants) but less on the role of <i>GHSR</i> variants. Several genetic causes of (partial) GHI are known (<i>GHR</i>, <i>STAT5B</i>, <i>STAT3</i>, <i>IGF1</i>, <i>IGFALS</i> defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.


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