Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.

Objectives: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. Design: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. Results: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity ðP , 0:05Þ; measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity ðP , 0:05Þ and increased skeletal muscle mass in comparison with controls ðP , 0:05Þ: Basal ACTH and corticosterone levels in LPS-treated rats were elevated ðP , 0:05Þ; as were corticosterone levels after exposure to a novel environment stress ðP , 0:05Þ: The adrenals were morphologically changed and enlarged ðP , 0:05Þ in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats ðP , 0:05Þ: Furthermore, circulating progesterone levels were lower ðP , 0:05Þ and testosterone tended to be higher. Conclusion:The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamicpituitary -adrenal and hypothalamic -pituitary -gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.

These data suggest that genetic variants of both the ERbeta and the PGR may influence prolactin release.

Objective: Glucocorticoids are important for normal brain development. Elevation or removal of these hormones can permanently modify the structure and function of the fetal brain. The purpose of this study was to examine the effects of postnatal corticosterone exposure of female pups on metabolic, endocrine and anthropometric variables in adulthood. Design: Female pups were given subcutaneous injections of corticosterone (5 mg/kg, CORT) or vehicle 3 and 5 days after birth. Results: From 6 weeks of age, the CORT rats weighed significantly less than did controls, with diminished fat depots, decreased serum levels of leptin and reduced food intake. Adult CORT rats showed increased insulin sensitivity, measured by hyperinsulinemic, euglycemic clamp (5 mU/kg/min), as compared with controls. CORT rats had lower basal corticosterone levels and lower corticosterone levels 15 and 90 min after exposure to stress. Conclusion:The results indicate that postnatal exposure to corticosterone leads to increased insulin sensitivity, low body weight with diminished fat depots, leptin and food intake. This suggests that postnatal exposure to corticosterone induces specific programming, with consequences in adult life.

In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reactionIn patients with panic disorder (Liebowitz et al. , 1985Pitts and McClure 1967) or premenstrual dysphoria (Facchinetti et al. 1992;Sandberg et al. 1993), but not in healthy controls, intravenous (i.v.) administration of sodium lactate elicits an anxiety reaction strongly resembling spontaneous panic attacks. The anxiogenic effect of sodium lactate has been attributed to changes in calcium concentrations (Pitts and McClure 1967), pH (Grosz andFarmer 1972), redox activity (Carr et al. 1986), pCO 2 (Gorman et al. 1988a), and osmolarity (Jensen et al. 1991;Peskind et al. 1998). However, all these theories and findings have also been questioned, and the mechanism by which sodium lactate elicits panic attacks hence is as yet unexplained.Likewise, the reason why patients with panic disorder or premenstrual dysphoria differ from controls with respect to sensitivity to lactate is a matter of controversy. Notably, a more rapid and substantial rise in brain lactate has been observed in panic patients as compared with control subjects (Dager et al. 1999), but the difference between patients and controls may also be due to different responsiveness to a given concentration (Pohl et al. 1994;Rifkin et al. 1981).Panic attacks are almost always associated with hyperventilation and respiratory discomfort, such as shortness of breath; it has thus been suggested that lactate-induced as well as spontaneous panic attacks may be due to an activation of a hyperresponsive suffocation alarm system involving activation of central or peripheral chemoreceptors (Klein 1993). Supporting this concept, an anxiety-provoking effect similar to that of lactate has been observed after inhalation of CO 2 in panic disorder subjects and in women with premenstrual dysphoria (Gorman et al. , 1988aGriez et al. 1987;Harrison et al. 1989;Kent et al. 2001;Papp et al. 1997;Perna et al. 1994;Woods et al. 1986).We have previously reported that intravenous administration of sodium lactate to Wistar rats, but not to rats of the Sprague-Dawley strain, elicits an increase in blood pressure and variable effects on heart rate (Wikander et al. 1995). Such cardiovascular response is in line with the assumption that lactate induces a stimulation of central or peripheral chemoreceptors. In the present study, the effect of sodium lactate on respiratory rate and tidal volume in freely moving, unrestrained male and female rats of the Wistar strain was explored. Given the previous reports suggesting that spontaneous panic attacks are menstrual cycle-dependent (Basoglu et al. 2000;Breier et al. 1986;Cameron et al. 1988;Cook et al. 1990;Klein 1993), that panic disorder may improve during pregnancy (Hertzberg and Wa...