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      Rising maternal circulating GH during murine pregnancy suggests placental regulation

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          Abstract

          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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          Most cited references36

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          Assessing reproductive status/stages in mice.

          The short reproductive cycle length observed in rodents, called the estrous cycle, makes them an ideal animal model for investigation of changes that occur during the reproductive cycle. Most of the data in the literature about the estrous cycle is obtained from rats because they are easily manipulated and they exhibit a clear and well-defined estrous cycle. However, the increased number of experiments using knockout mice requires identification of their estrous cycle as well, since (in)fertility issues may arise. In mice, like rats, the identification of the stage of estrous cycle is based on the proportion of cell types observed in the vaginal secretion. The aim of this unit is to provide guidelines for quickly and accurately determining estrous cycle phases in mice. Copyright 2009 by John Wiley & Sons, Inc.
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            Ghrelin octanoylation mediated by an orphan lipid transferase.

            The peptide hormone ghrelin is the only known protein modified with an O-linked octanoyl side group, which occurs on its third serine residue. This modification is crucial for ghrelin's physiological effects including regulation of feeding, adiposity, and insulin secretion. Despite the crucial role for octanoylation in the physiology of ghrelin, the lipid transferase that mediates this novel modification has remained unknown. Here we report the identification and characterization of human GOAT, the ghrelin O-acyl transferase. GOAT is a conserved orphan membrane-bound O-acyl transferase (MBOAT) that specifically octanoylates serine-3 of the ghrelin peptide. Transcripts for both GOAT and ghrelin occur predominantly in stomach and pancreas. GOAT is conserved across vertebrates, and genetic disruption of the GOAT gene in mice leads to complete absence of acylated ghrelin in circulation. The occurrence of ghrelin and GOAT in stomach and pancreas tissues demonstrates the relevance of GOAT in the acylation of ghrelin and further implicates acylated ghrelin in pancreatic function.
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              Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women.

              To assess the longitudinal changes in insulin release and insulin sensitivity in nonobese normal women during gestation, six women were evaluated with oral glucose tolerance testing, body composition analysis, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp before conception, at 12 to 14 weeks, and at 34 to 36 weeks' gestation. There was a significant increase in the insulin/glucose ratio (p = 0.028) during the oral glucose tolerance test during gestation. There was also a significant 3.0- to 3.5-fold increase throughout gestation in first-phase (p = 0.001) and second-phase (p = 0.0001) insulin release during the intravenous glucose tolerance test. Peripheral insulin sensitivity was estimated as the glucose infusion rate (in milligrams per kilogram fat-free mass per minute) during the hyperinsulinemic-euglycemic clamp. There was a significant (p = 0.0003) 56% decrease in insulin sensitivity through 36 weeks' gestation. These results are the first to prospectively evaluate the longitudinal changes in maternal carbohydrate metabolism from the time before conception through late gestation with newer methods such as the hyperinsulinemic-euglycemic clamp.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2017
                12 April 2017
                : 6
                : 4
                : 260-266
                Affiliations
                [1 ]Robinson Research Institute The University of Adelaide, Adelaide, Australia
                [2 ]Adelaide Medical School The University of Adelaide, Adelaide, Australia
                [3 ]FOOD plus Research Centre School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, Australia
                [4 ]School of Biomedical Sciences University of Queensland, St Lucia, Brisbane, Australia
                [5 ]Endocrine Research Unit Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA
                Author notes
                Correspondence should be addressed to K L Gatford; Email: kathy.gatford@ 123456adelaide.edu.au
                Article
                EC170032
                10.1530/EC-17-0032
                5457489
                28404685
                06d7bce1-75d9-4b95-b2b7-0630abf10908
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 11 April 2017
                : 12 April 2017
                Categories
                Research

                mouse,pregnancy,growth hormone,profile,placenta
                mouse, pregnancy, growth hormone, profile, placenta

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