Annica Sohlström

Postnatal Oxytocin Injections Cause Sustained Weight Gain and Increased Nociceptive Thresholds in Male and Female Rats

The aim of the present study was to investigate possible long-term effects of postnatally administered oxytocin on weight gain, gastrointestinal hormone levels, and nociceptive thresholds in rats. For this purpose, s.c. daily injections of oxytocin (1 mg/kg) or saline (NaCl, 0.9%) were given to male and female rat pups on d 10-14 after birth. The animals were killed at the age of 60 or 94 d. Treatment with oxytocin resulted in higher body weight in males, 60 d after birth, and in females from d 60 and throughout the rest of the experiment, compared with controls. The higher body weight was due to an increased weight gain in oxytocin-treated rats, compared with controls, which was most pronounced between 40 and 60 d after birth. Oxytocin-treated male rats had increased circulating levels of cholecystokinin, a tendency to increased plasma levels of insulin (p = 0.066), and relatively more adipose tissue in the thigh and interscapular region, compared with controls. At the age of 60 d, oxytocin-treated female and male rats had a prolonged withdrawal latency when measured in the tail-flick test, compared with controls. This study shows that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.

Food restriction alters pregnancy-associated changes in IGF and IGFBP in the guinea pig

The effect of moderate food restriction on pregnancy-associated changes in weight gain, body composition, and circulating insulin-like growth factors (IGF) I and II and IGF-binding proteins (IGFBP)-1 through-4 and their relationship was determined in the guinea pig. Pregnancy did not stimulate weight gain but reduced fat deposition in ad libitum-fed animals and increased weight gain and fat deposition in food-restricted animals relative to their respective virginal group. Pregnancy increased the abundance of circulating IGF-I regardless of food intake and increased that of IGF-II in food-restricted animals only. Pregnancy also increased circulating IGFBP-1 and -2 in ad libitum-fed and food-restricted animals and IGFBP-4 in ad libitum-fed animals. Multiple regression analysis showed that maternal weight gain was negatively associated with circulating IGF-II and IGFBP-2. Fetal weight was positively associated with maternal circulating IGF-II and negatively associated with maternal circulating IGFBP-1 and -2. Significant interactions indicate, however, that the role of IGF-II and IGFBP-1 on fetal growth is dependent on the nutritional status of the mother.The effect of moderate food restriction on pregnancy-associated changes in weight gain, body composition, and circulating insulin-like growth factors (IGF) I and II and IGF-binding proteins (IGFBP)-1 through -4 and their relationship was determined in the guinea pig. Pregnancy did not stimulate weight gain but reduced fat deposition in ad libitum-fed animals and increased weight gain and fat deposition in food-restricted animals relative to their respective virginal group. Pregnancy increased the abundance of circulating IGF-I regardless of food intake and increased that of IGF-II in food-restricted animals only. Pregnancy also increased circulating IGFBP-1 and -2 in ad libitum-fed and food-restricted animals and IGFBP-4 in ad libitum-fed animals. Multiple regression analysis showed that maternal weight gain was negatively associated with circulating IGF-II and IGFBP-2. Fetal weight was positively associated with maternal circulating IGF-II and negatively associated with maternal circulating IGFBP-1 and -2. Significant interactions indicate, however, that the role of IGF-II and IGFBP-1 on fetal growth is dependent on the nutritional status of the mother.

Longitudinal Study of the Maternal Insulin-Like Growth Factor System before, during and after Pregnancy in Relation to Fetal and Infant Weight

Background: The maternal insulin-like growth factor (IGF) system is considered to be involved in fetal growth regulation. However, available data linking this system to fetal growth are contradictory and incomplete. Aims: To measure components of the IGF system before, during and after pregnancy in healthy women and to relate these results, and their changes during pregnancy, to fetal weight (gestational week 31) and birth weight. Methods: Serum concentrations of IGF-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and IGFBP-3 protease activity were assessed in 23 women before conception, at weeks 8, 14, 20, 32 and 35 of pregnancy and 2 weeks postpartum. The data were analyzed using simple and multiple linear regression. Results: One third of the variability in fetal weight was explained by IGF-I in combination with IGFBP-3 protease activity, both assessed at gestational week 32 (p = 0.013). Birth weight was negatively correlated (r = –0.43 to –0.59) with IGFBP-1 at gestational week 20 (p = 0.041), 32 (p = 0.012) and 35 (p = 0.003). Conclusion: We propose there is a finely tuned balance among the components of the IGF system, providing a means for fetal growth regulation.

Oxytocin Treatment during Early Life Influences Reproductive Performance in ad libitum Fed and Food-Restricted Female Rats

Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother’s previous and current nutritional experience.

Long-Term Modulation By Postnatal Oxytocin of the α2-Adrenoceptor Agonist Binding Sites in Central Autonomic Regions and the Role of Prenatal Stress

The aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life‐long effects on the α2‐agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the α2‐agonist [3H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of α2‐agonist binding sites in the NTS and in the hypothalamus. The Kd value of the α2‐agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food‐restricted dams, oxytocin treatment produced a significant increase of the Bmax values in the hypothalamus and the amygdala and the Kd value of the α2‐agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin‐induced increase of regional α2‐adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central α2‐adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of α2‐adrenoceptor signalling in adulthood may contribute to the anti‐stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in α2‐adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the α2‐agonist binding sites in the hypothalamus and the amygdala.

Maternal serum concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-1 before and during pregnancy in relation to maternal body weight and composition and infant birth weight

Maternal nutritional status, e.g. body weight and composition, is associated with fetal growth. It has been suggested that the insulin-like growth factor (IGF) system may be a mediator of this relationship. In twenty-three healthy Swedish women, we studied (1) the relationships before and during pregnancy between maternal serum concentrations of IGF-I and IGF binding protein-1 (IGFBP-1) and maternal body weight and composition; (2) interactions between serum concentrations of IGF-I (before and in early pregnancy) and maternal nutritional status in relation to infant birth weight. We found that serum IGF-I during pregnancy was positively correlated with maternal body weight (r 0.47-0.56) and fat-free body weight (r 0.61-0.65), whereas serum IGFBP-1 was negatively correlated with maternal body weight (r - 0.44 to - 0.69) and body fat (r - 0.64 to - 0.76) before and during pregnancy. Women with a lower body fat content (%) before pregnancy had greater increases in serum IGFBP-1 during pregnancy than women with a higher prepregnant body fat content (%). In addition, significant fractions of the variation in corrected infant birth weight were explained by variables related to the maternal nutritional status when these were combined with serum concentrations of IGF-I in gestational week 14 (adjusted r2 0.25-0.44, P = 0.001-0.021), but not when they were combined with such concentrations before pregnancy (adjusted r2 0.11-0.12, P = 0.105-0.121). These results suggest mechanisms by which the IGF system may be a mediator between maternal nutritional status and fetal growth.

Effects of Oxytocin Treatment Early in Pregnancy on Fetal Growth in ad Libitum -Fed and Food-Restricted Rats

The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. We suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.