| 1. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Prenatal cytokine exposure results in obesity and gender-specific programming.
- 2001
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Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 281:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Eriksson, Elias, 1956, et al.
(författare)
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Diagnosis and treatment of premenstrual dysphoria.
- 2002
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Ingår i: The Journal of clinical psychiatry. - 0160-6689. ; 63 Suppl 7, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome afflicting 5% to 10% of all fertile women. Cardinal symptoms--appearing regularly between ovulation and menstruation and disappearing within a few days after the onset of the bleeding--are depressed mood, tension, affect lability, and irritability. Of these symptoms, irritability is often the most prominent. Serotonin reuptake inhibitors (SRIs), but not nonserotonergic antidepressants, reduce the symptoms of PMD effectively. The onset of action of SRIs is much shorter when used for PMD than when used for depression, enabling women with PMD to restrict medication use to the luteal phase of the cycle (so-called intermittent treatment). The findings that SRIs are effective for PMD--and that sexual dysfunction is the most frequent side effect during long-term treatment--both lend support for the hypothesis that a major role for brain serotonin is to modulate sex steroid-driven behavior.
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| 3. |
- Ho, Hoi-Por, 1962, et al.
(författare)
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Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women.
- 2004
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 58:2, s. 109-110
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Tidskriftsartikel (refereegranskat)abstract
- Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.
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| 4. |
- Ho, Hoi-Por, 1962
(författare)
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On the biology of premenstrual dysphoria and panic disorder
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Premenstrual dysphoria (PMD) afflicts 7% of all women of fertile age, and is characterized by symptoms such as irritability, sadness, and mood swings, appearing regularly before menstruation, and being of such severity that they markedly reduce quality of life. The symptoms are dependent of sex steroids, and seem to be under the influence of serotonin, since they respond to treatment with serotonin reuptake inhibitors (SRIs). Panic disorder (PD) afflicts 3% of the population, and is characterized by anxiety attacks, often dominated by respiratory symptoms. PD is more common in women than in men, and fluctuations in levels of sex steroids have been reported to influence the symptom intensity. Like patients with PMD, subjects with PD respond to treatment with SRIs. PMD and PD also display other similarities; both diagnoses hence are associated with enhanced respiratory variability, and with an enhanced sensitivity to the anxiety-provoking effects of CO2 and lactate. One purpose of this work was to develop an animal model of premenstrual irritability, and to use this to elucidate the role of serotonin and sex steroids for this condition. In order to shed further light on the respiratory abnormalities characterizing both PMD and PD, and the possible role of the estrus cycle in this context, we also studied respiratory rate, tidal volume and respiratory variability in freely moving rats. Finally, a third purpose, prompted by the suggestion that progesterone, by influencing respiration, is involved in the pathophysiology of PD, was to examine to what extent PMD and PD are associated with polymorphisms in the progesterone receptor gene. Results: Some but not all female Wistar rat displayed aggressive behavior in the resident intruder paradigm during the non-receptive phase of the cycle. Like the symptoms of PMD, this behavior was abolished by ovariectomy, and reinstated - in rats that had displayed aggression before gonadectomy - by exogenous sex steroids. Treatment with two different SRIs was shown to reduce estrus cycle-related aggression; this effect was observed rapidly after drug administration, unabated during long-term treatment, and partially counteracted by a 5-HT1A antagonist. Tentatively corresponding to SRI-induced reduced in libido in humans, a reduction in sexual motivation was observed in SRI-treated rats. Respiratory rate was shown to be estrus cycle-dependent, but only in rats showing cycle-related aggression; these animals also displayed enhanced respiratory variability. Aggressive and non-aggressive rats also differed with respect to brain monoamine metabolism, but not with respect to sex steroids in serum. PD in women, but not PMD, was associated with a promoter polymorphism (G331A) in the progesterone receptor gene. Conclusion: It is suggested that estrus cycle-related aggression in a subgroup of female Wistar rats corresponds to premenstrual irritability. An enhanced brain responsiveness to sex steroids is suggested to influence both aggression and respiration, and may tentatively be due either to an increase in sex steroid receptor responsiveness or to a dysfunction in serotonergic neurons mediating or modulating the effects of sex steroids. The possible relevance of these findings and hypotheses for the biology of PD and PMD is being discussed.
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| 5. |
- Ho, Hoi-Por, 1962, et al.
(författare)
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The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability?
- 2001
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - 0893-133X. ; 24:5, s. 502-10
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Tidskriftsartikel (refereegranskat)abstract
- The aggressive behavior displayed by some (but not all) female Wistar rats when an unfamiliar rat is being introduced into their home cage (the resident intruder paradigm) was found to be higher in non-receptive phases (metestrus, diestrus) than in the receptive phases (proestrus, estrus) of the estrus cycle, and effectively reduced by ovariectomy. When removal of the ovaries was followed by administration of estradiol and progesterone, in a regimen mimicking the normal cyclical release of these hormones, aggressive behavior was elicited, two days after estrus, in animals that had displayed aggressive behavior before ovariectomy, but not in those that had not. Short-term administration of a serotonin reuptake inhibitor (fluoxetine hydrochloride; 10 mg/kg, i.p.; 4-5 days) reduced both the aggressive behavior displayed during the diestrus phase by normally cycling rats, and the aggressive behavior elicited by administration of estradiol plus progesterone after ovariectomy. It is suggested that the aggressive behavior displayed by the female Wistar rat in the resident intruder paradigm may serve as an animal model of premenstrual dysphoria.
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| 6. |
- Melchior, Lydia K, 1979, et al.
(författare)
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Association between estrus cycle-related aggression and tidal volume variability in female Wistar rats.
- 2004
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 29:8, s. 1097-100
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoria is characterized by symptoms such as irritability and depressed mood, present during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Subjects with premenstrual dysphoria have previously been reported to display enhanced respiratory variability, and to experience anxiety when exposed to panicogens, such as CO2. In the present study, the possible influence of the estrus cycle and estrus cycle-related aggression on respiratory variability was investigated in female rats of the Wistar strain. The rats were subdivided into two groups: those displaying estrus cycle-related aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the estrus cycle. This model has been developed to serve as an animal model of premenstrual irritability. The former group was found to display higher tidal volume variability in diestrus, as compared to the non-aggressive rats. There was no effect of estrus cycle phase on respiratory variability. These results are well in line with the clinical observation that women with premenstrual dysphoria display higher respiratory variability than controls, and the notion that respiratory variability is a parameter of interest in this context. In our opinion, they also strengthen the concept of this animal model as a model of premenstrual irritability.
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| 7. |
- Nilsson, Cecilia, et al.
(författare)
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Increased insulin sensitivity and decreased body weight in female rats after postnatal corticosterone exposure.
- 2002
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 146:6, s. 847-54
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Nilsson, Cecilia, et al.
(författare)
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Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.
- 2002
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 146:2, s. 251-60
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Tidskriftsartikel (refereegranskat)abstract
- 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 (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) 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 (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) 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 hypothalamic-pituitary-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.
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| 9. |
- Nilsson, Cecilia, et al.
(författare)
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Reductions in adipose tissue and skeletal growth in rat adult offspring after prenatal leptin exposure.
- 2003
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 176:1, s. 13-21
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is involved in regulating food intake, energy balance and bone formation. Increasing evidence suggests that leptin is also involved in fetal growth and development. The aim of this study was to determine if increased maternal leptin is followed by changes in body composition, skeletal growth or hormonal regulation in the adult rat offspring. Pregnant rats were given injections of either human recombinant leptin (3.5 mg/kg, i.p.) or vehicle on days 8, 10 and 12 of gestation. Both genders of leptin-exposed offspring showed significantly reduced adipose tIssue weight at adult age. Skeletal growth and cortical bone dimensions were significantly reduced. Circulating testosterone levels were significantly increased in female leptin-exposed offspring, and male leptin-exposed offspring had significant testicular enlargement. No significant effects were seen on circulating leptin levels or hypothalamic protein levels of the leptin receptor. The results demonstrate that maternally administered leptin is involved in fetal growth and development, leading to lean offspring with reduced skeletal growth.
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| 10. |
- Olsson, Marie, 1971, et al.
(författare)
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Association between estrus cycle-related changes in respiration and estrus cycle-related aggression in outbred female Wistar rats.
- 2003
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 28:4, s. 704-10
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual dysphoric disorder is characterized by irritability surfacing during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Although the cardinal symptoms of premenstrual dysphoria are different from those of panic disorder, the two conditions share a number of traits indicating that they both may be associated with abnormalities in the regulation of respiration. Both subjects with panic disorder and subjects with premenstrual dysphoria are hence reported to display enhanced respiratory variability, and to experience anxiety when exposed to CO(2). In the present study, the possible influence of the estrus cycle on respiratory parameters in outbred female rats of the Wistar strain was investigated. Before being tested with respect to respiration, the rats were subdivided into two groups: those displaying estrus cycle-related variation in aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the cycle. Whereas the former group was found to display higher respiratory rate during the diestrus phase than during the proestrus/estrus phase, no cycle-related variation in respiration was observed in animals not showing cycle-related variation in aggression. The results support previous studies indicating that the estrus cycle exerts an influence on respiration, and suggest that rats prone to cycle-related aggression are more sensitive also to the influence of hormonal cyclicity on respiration. The possible bearing of these findings for the aberration in respiration displayed by subjects with premenstrual dysphoria is discussed.
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