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      The relationship between weight gain during pregnancy and allopregnanolone levels: a longitudinal study

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          Abstract

          Objective

          Large weight gain during pregnancy is a risk factor for complications for mother and fetus. Hunger and satiety are regulated in the hypothalamus, where the gamma-amino-butyric acid system (GABA) has an important role. Allopregnanolone, a progesterone metabolite, increases during pregnancy and is a potent GABA-A receptor modulating steroid. Allopregnanolone has been shown to induce overeating in rodents. The aim was to investigate whether there is a relationship between weight gain and allopregnanolone concentrations during pregnancy in humans.

          Design

          A longitudinal, cohort study.

          Methods

          Pregnant women ( n = 56) were recruited in primary care in northern Sweden. Allopregnanolone concentrations in plasma were measured using radioimmunoassay and weight was measured in gestational weeks 12 and 35.

          Results

          Weight increase correlated significantly to allopregnanolone in late pregnancy increase ( r s = 0.320; P = 0.016), indicating a positive relationship between weight increase and allopregnanolone increase. A positive relationship was also noted between allopregnanolone in the 35th gestational week and weight increase. Women who gained ≥11 kg during pregnancy showed higher allopregnanolone concentrations in week 35 and higher increase compared to women who increased <11 kg ( P = 0.006 and P = 0.009 resp.). There was no difference in weight or allopregnanolone concentrations at the onset of pregnancy.

          Conclusions

          The results show a relationship between weight gain during pregnancy and increase in allopregnanolone concentrations.

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          Most cited references35

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          Neuroactive steroids.

          S Paul, R Purdy (1992)
          Neuroactive steroids are natural or synthetic steroids that rapidly alter the excitability of neurons by binding to membrane-bound receptors such as those for inhibitory and (or) excitatory neurotransmitters. The best-studied neuroactive steroids are a series of sedative-hypnotic 3 alpha-hydroxy ring A-reduced pregnane steroids that include the major metabolites of progesterone and deoxycorticosterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydroDOC), respectively. These 3 alpha-hydroxysteroids do not interact with classical intracellular steroid receptors but bind stereoselectively and with high affinity to receptors for the major inhibitory neurotransmitter in brain, gamma-amino-butyric acid (GABA). Biochemical and electrophysiological studies have shown that these steroids markedly augment GABA-activated chloride ion currents in a manner similar (but not identical) to that of anesthetic barbiturates. Several steroids have also been observed to have convulsant or proconvulsant properties, including the synthetic amidine 3 alpha-hydroxy-16-imino-5 beta-17-azaandrostan-11-one (RU5135) and the natural sulfate esters of pregnenolone and dehydroepiandrosterone. Several of these have been shown to be bicuculline or picrotoxin-like GABAA receptor antagonists. Examples of steroids that alter neuronal excitability rapidly by augmenting or inhibiting excitatory amino acid receptor-mediated responses have also been reported. Recently, allopregnanolone and allotetrahydroDOC have also been measured in brain and plasma where their levels have been shown to fluctuate in response to stress and during the estrous and menstrual cycles of rats and humans, respectively. Although the major fraction of allopregnanolone in tissue, including brain, is of adrenal and/or ovarian origin, appreciable levels of allopregnanolone can still be measured in the brains of adrenalectomized and/or oophorectomized animals. Receptor-active neurosteroids may represent an important class of neuromodulators that can rapidly alter central nervous system excitability via novel nongenomic mechanisms.
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            Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues.

            Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320-425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time- or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation.
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              Eating patterns and portion size associated with obesity in a Swedish population.

              The objective of this study was to describe the association between meal pattern and obesity. The study is based on data from the INTERGENE research programme, and the study population consists of randomly selected women and men, aged 25-74, living in the Västra Götaland Region in Sweden. A total of 3610 were examined. Participants with measured BMI> or =30 were compared with others (BMI<30) with respect to questionnaire data on habitual meal patterns and intake of energy estimated from food frequencies and standard portions. Odds ratios (OR) with 95% confidence intervals were adjusted for age, sex, smoking and physical activity in logistic regression models. Being obese was significantly associated with omitting breakfast, OR 1.41 (1.05-1.90), omitting lunch OR 1.31 (1.04-1.66) and eating at night OR 1.62 (1.10-2.39). Obesity was also related to significantly larger self-reported portion sizes of main meals. No statistically significant relationship with intake of total energy was revealed. Thus, the results indicate that examination of meal patterns and portion sizes might tell us more about obesogenic food patterns than traditional nutrient analyses of food frequencies. Being obese was associated with a meal pattern shifted to later in the day and significantly larger self-reported portions of main meals.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2017
                05 April 2017
                : 6
                : 4
                : 253-259
                Affiliations
                [1 ]Department of Public Health and Clinical Medicine Family Medicine, Umeå University, Umeå, Sweden
                [2 ]Department of Clinical Sciences Obstetrics and Gynecology, Umeå University, Umeå, Sweden
                Author notes
                Correspondence should be addressed to A Lundqvist; Email: anette.lundqvist@ 123456umu.se
                Article
                EC170046
                10.1530/EC-17-0046
                5632720
                28381564
                3e331e3e-24b9-4ab6-959a-af046a85c08a
                © 2017 The authors

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

                History
                : 30 March 2017
                : 5 April 2017
                Categories
                Research

                allopregnanolone,pregnancy,weight increase,longitudinal
                allopregnanolone, pregnancy, weight increase, longitudinal

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