Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice

Trivedi, Arjun; Babic, Sandra; Heiman, Mark L.; Gibson, William T.; Chanoine, Jean‐Pierre

doi:10.1016/j.peptides.2015.01.005

Cited by 7 publications

(12 citation statements)

References 32 publications

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“…One key aspect is that, unlike humans, rodents do not produce the GH-V (40,52). In spite of that, plasma GH levels are robustly elevated in late-pregnant mice and rats (23,32,77). However, the mechanisms associated with these increased circulating GH levels observed in pregnant rodents are unclear since decreased expression of Ghrh mRNA in the ARH and increased expression of somatostatin mRNA in the periventricular nucleus were observed in pregnant rats relative to virgin controls (23).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanisms associated with these increased circulating GH levels observed in pregnant rodents are unclear since decreased expression of Ghrh mRNA in the ARH and increased expression of somatostatin mRNA in the periventricular nucleus were observed in pregnant rats relative to virgin controls (23). Additionally, previous studies rule out an involvement of ghrelin-induced GH secretion during pregnancy and have shown evidence that GH is probably not secreted by the placenta (23,77). Therefore, even though rodents do not possess a gene analogous to Gh2 and consequently cannot produce GH-V, GH is highly secreted in pregnant mice and the lack of GHR in the brain affects gestational metabolic adaptations.…”

Section: Discussionmentioning

confidence: 99%

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Central growth hormone action regulates metabolism during pregnancy

Teixeira

Couto

Furigo

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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The maternal organism undergoes numerous metabolic adaptations to become prepared for the demands associated with the coming offspring. These metabolic adaptations involve changes induced by several hormones that act at multiple levels, ultimately influencing energy and glucose homeostasis during pregnancy and lactation. Previous studies have shown that central growth hormone (GH) action modulates glucose and energy homeostasis. However, whether central GH action regulates metabolism during pregnancy and lactation is still unknown. In the present study, we generated mice carrying ablation of GH receptor (GHR) in agouti-related protein (AgRP)–expressing neurons, in leptin receptor (LepR)–expressing cells or in the entire brain to investigate the role played by central GH action during pregnancy and lactation. AgRP-specific GHR ablation led to minor metabolic changes during pregnancy and lactation. However, while brain-specific GHR ablation reduced food intake and body adiposity during gestation, LepR GHR knockout (KO) mice exhibited increased leptin responsiveness in the ventromedial nucleus of the hypothalamus during late pregnancy, although their offspring showed reduced growth rate. Additionally, both Brain GHR KO and LepR GHR KO mice had lower glucose tolerance and glucose-stimulated insulin secretion during pregnancy, despite presenting increased insulin sensitivity, compared with control pregnant animals. Our findings revealed that during pregnancy central GH action regulates food intake, fat retention, as well as the sensitivity to insulin and leptin in a cell-specific manner. Together, the results suggest that GH acts in concert with other “gestational hormones” to prepare the maternal organism for the metabolic demands of the offspring.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Central growth hormone action regulates metabolism during pregnancy

Teixeira

Couto

Furigo

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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“…The role of endogenous acyl-ghrelin in GH regulation has been studied in mice lacking Mboat4 (membrane-bound O-acyl transferase 4), the enzyme responsible for octanoylating ghrelin to produce active acyl-ghrelin (35). The recent study of Trivedi and coworkers, in which a single sample of maternal blood was collected from each mouse 18 days after mating, at 0930 h, 4 h after lights on, showed normal increases in maternal circulating GH during pregnancy in the Mboat4 -knockout mouse (11), although it is possible that the circulating pattern is perturbed. This contrasts with decreased GH secretion in young male Mboat4 -knockout mice (40) and suggests that acyl-ghrelin is not the driver of pregnancy-associated GH increases in the pregnant mouse.…”

Section: Discussionmentioning

confidence: 99%

“…In this species, GH remains pulsatile throughout pregnancy, with relatively unchanged pulsatile secretion superimposed on progressively increasing basal secretion (10). In the pregnant mouse, GH measured in single samples increases 30- to 50-fold near term (11), but the patterns of circulating GH during pregnancy have not been reported. Studies in mouse may allow interrogation of regulatory systems through use of knockout and other mutant strains, but first require an understanding of the normal ontogeny of the GH axis during murine pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Rising maternal circulating GH during murine pregnancy suggests placental regulation

Gatford

Mühlhäusler

Huang

et al. 2017

Endocrine Connections

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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.

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“…Our investigations of the role of GOAT in pregnant animals have shed light on the respective effects of AG and GH on glucose control. We have previously reported that rodent pregnancy is characterized by a marked increase in circulating GH from pituitary origin that is 35-46-fold greater than seen in non-pregnant animals [50]. This GH increase takes place in both WT and GOAT-KO animals, in the absence of significant changes in GOAT activity, in ghrelin expression in the stomach or hypothalamus, or in circulating AG or UAG.…”

Section: Discussionmentioning

confidence: 88%

Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice

Trivedi

Babic

Heiman³

et al. 2016

Horm Metab Res

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Acylation of ghrelin is mediated by ghrelin acyltansferase (GOAT). Exogenous acylated ghrelin (AG) stimulates growth hormone (GH) and food intake. In non-pregnant (NP) animals, the GOAT-ghrelin-GH axis prevents hypoglycemia caused by caloric restriction (CR). In humans, maternal malnutrition challenges glucose metabolism, which is a key determinant of fetal health. To clarify the role of AG and GH, we compared effects of CR on the GOAT-ghrelin-GH axis in pregnant (P) and NP mice. C57BL/6 wild type (WT) and GOAT knock-out (KO) P and NP mice were freely fed (FF) or subjected to 50% CR for one week. CR was started in P mice on Day 10.5 after conception. We measured body composition, blood glucose, plasma ghrelin and GH, stomach, hypothalamus and pituitary GOAT and ghrelin expression, and liver glycogen content and expression. GOAT and AG were undetectable in KO. In NP mice, CR did not affect blood glucose (-1.3 mmol/l, p>0.05) in WT but was lowered (-1.8 mmol/l, p<0.0001) in KO. GH and mRNA expression increased in WT but not in KO. In P mice, CR markedly lowered glucose (-2.7 mmol/l; p<0.0001) in WT and caused fatal hypoglycemia in KO, despite similarly elevated GH in WT and KO mice. KO animals are more prone to hypoglycemia than WT. GH, which is high in P animals, does not prevent hypoglycemia caused by CR during pregnancy. Our data suggest a specific role of AG in the regulation of gluconeogenesis to maintain euglycemia during pregnancy when energy availability is limited.

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Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice

Abstract: The complete absence of ghrelin acylation, which is associated with undetectable AG concentrations, does not prevent the marked increase in pituitary GH concentrations observed in pregnant mice, suggesting that AG is not the major mediator of GH secretion during pregnancy.

Cited by 7 publications

References 32 publications

Central growth hormone action regulates metabolism during pregnancy

Central growth hormone action regulates metabolism during pregnancy

Rising maternal circulating GH during murine pregnancy suggests placental regulation

Ghrelin, Ghrelin O-Acyltransferase, and Carbohydrate Metabolism During Pregnancy in Calorie-Restricted Mice

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