Biomedical subjects

Anastasia Kariagina

Publications and source records attributed to Anastasia Kariagina.

8 recordsLinked to original sources

PubMed2006

Developmental exposure to corticosterone: behavioral changes and differential effects on leukemia inhibitory factor (LIF) and corticotropin-releasing hormone (CRH) gene expression in the mouse.

RATIONALE: Cytokines are found in both the peripheral and central nervous system. There has been increasing interest in their potential role in some of the behavioral features of depressive disorders. Leukemia inhibitory factor (LIF), a proinflammatory cytokine, produces stimulation of adrenocorticotropic hormone (ACTH) secretion in response to emotional and inflammatory stress and recently has been linked to depressive-type behavior. Both the hypothalamic-pituitary-adrenal axis and the immune system, including cytokine-mediated responses, appear to be susceptible to long-term programming during fetal and neonatal development. OBJECTIVE: The present study was designed to characterize the effects of perinatal exposure to corticostereone on behavior, hypothalamic LIF and corticotropin-releasing hormone (CRH) mRNA expression, and basal plasma corticosterone levels in adult female mice. METHODS: Corticosterone was added to the drinking water beginning the last week of gestation and continued until weaning. Behavior in the open field and forced swim tests, baseline plasma corticosterone levels, and hypothalamic LIF and CRH gene expression were evaluated in the adult offspring. RESULTS: Mice exposed to perinatal corticosterone showed increased immobility in the forced swim test and increased locomotor activity in the open field test. Although there were no differences between treatment groups in terms of basal plasma levels of corticosterone or hypothalamic CRH mRNA, LIF mRNA expression was increased in the hypothalamus. CONCLUSIONS: These results show that perinatal exposure to glucocorticoids can produce long-term behavioral changes and upregulation of central LIF mRNA expression.

Animals↗

PubMed2005

Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis.

Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+ fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the importance of LIF signaling for HPA axis development.

Adrenocorticotropic Hormone↗

PubMed2005

Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis.

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 microg/mouse, i.p.) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation.

Animals↗

PubMed2005

Progesterone receptor isoforms A and B: temporal and spatial differences in expression during murine mammary gland development.

Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2'-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.

Animals↗

PubMed2004

Reduced immobility in the forced swim test in mice with a targeted deletion of the leukemia inhibitory factor (LIF) gene.

Cytokines are a large and diverse group of polypeptides that are rapidly released in response to tissue injury, infection, and inflammation. Besides their effects in the periphery, cytokines also affect the central nervous system (CNS). There has been increasing interest in the potential role of cytokines in the behavioral features of depressive disorders. One cytokine that might be a candidate for a role in the etiology of depression is leukemia inhibitory factor (LIF). LIF mRNA has been detected in the hypothalamus, hippocampus, amygdala, cerebellum, cerebral cortex, and basal forebrain nuclei. The role of LIF in the CNS has not been fully elucidated. Based upon the hypothesis that cytokines might have a role in depression, the present study characterized the behavior of mice with a targeted disruption of the LIF gene (LIF knockouts) in the forced swim test, an animal model used to measure depressive-like behavior and the response to antidepressants. It was found that LIF knockout mice show reduced immobility in the forced swim test, suggesting that LIF might have a potential role in the etiology of some forms of depression.

Analysis of Variance↗

PubMed2003

Hypothalamic-pituitary cytokine network.

Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 microg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P<0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFalpha, IL-1beta, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.

Adrenocorticotropic Hormone↗

PubMed2002

Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation.

We have shown that leukemia inhibitory factor (LIF) and suppressor of cytokine signaling (SOCS)-3 are expressed in the hypothalamus and pituitary and that LIF induces proopiomelanocortin (POMC) and ACTH, whereas SOCS-3 abrogates corticotroph POMC gene transcription and ACTH secretion. Here, we determined the role of pituitary LIF and SOCS-3 in regulating hypothalamo-pituitary-adrenal (HPA) axis inflammatory responses. Murine pituitary LIF expression was induced up to eightfold after intraperitoneal injection of lipopolysaccharide or tumor necrosis factor-alpha, concordant with elevated plasma levels of ACTH and corticosterone. In LIF knockout (LIFKO) mice, induction of both ACTH and corticosterone were attenuated. LIF deletion was associated with elevated (P < 0.05) levels of pituitary TNF-alpha, interleukin (IL)-1beta, and IL-6 mRNA and cytokine-inducible pituitary SOCS-3 expression. Abrogation of the HPA axis stress response and higher pituitary levels of proinflammatory cytokines observed in LIFKO mice resulted in a stronger inflammatory process, as evidenced by elevated erythrocyte sedimentation rate and increased serum amyloid A levels (P < 0.05). The results indicate that, although LIF induces ACTH, SOCS-3 acts to counterregulate the HPA axis response to inflammation.

Acute Disease↗

PubMedDate not supplied

Progestins and breast cancer.

Progesterone (P) regulates proliferation and differentiation in the normal mammary gland in mouse, rat and human. Progesterone has also been implicated in the etiology and pathogenesis of human breast cancer. The focus of this review is on recent advances in understanding the role of the progesterone receptor (PR) and functional significance of PR isoforms, PRA and PRB, in the normal mammary gland and in mammary cancer in mouse, rat and human.

Animals↗