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Biomedical subjects

F Stylianopoulou

Publications and source records attributed to F Stylianopoulou.

At least 37 records · Page 2Linked to original sources

Maternal behavior of dams treated with ACTH during pregnancy.

Experimental female rats were injected with ACTH during the last third of their pregnancy. This treatment resulted in prolongation of gestation and in abnormal development of the young. The number of resorptions, stillbirths, and congenitally malformed pups was increased and those that appeared normal had lower body weights. The experimental treatment also severely affected the ability of the dams to exhibit normal maternal behavior. Significant individual differences were noted in the sensitivity of the dams to the experimental treatment. Cross-fostering experiments revealed that experimental dams exhibited normal maternal behavior towards control foster pups, after an initial delay of 24 h. When experimental pups, born after a prolonged gestation, or delivered by caesarian section after the normal duration of gestation, were given to control mothers, normal maternal behavior was observed, but the survival rate of the young was not increased.

Abnormalities, Drug-Induced↗

Effects of hyperactivity of the maternal hypothalamic-pituitary-adrenal (HPA) axis during pregnancy on the development of the HPA axis and brain monoamines of the offspring.

Offspring of mothers with adrenal hyperactivity during pregnancy have been reported to have changes in brain monoamines and altered emotional, reactive, sexual and maternal behavior. Since the hypothalamic-pituitary-adrenal (HPA) axis is known to be involved in the expression of such behaviors and is itself under monoaminergic control, we examined the development of the HPA axis and brain monoamines in pups whose mothers had adrenal hyperactivity, reflecting administration of ACTH during the last third of their pregnancy. The adrenals of the experimental animals weighed less and had aberrant morphology. The abnormal histology was more pronounced in the adrenals of the experimental females than of the males, suggesting that females were more vulnerable to the prenatal treatment. In both experimental males and females, basal plasma corticosterone levels were higher compared to the controls, while after exposure to stress, experimental animals attained lower plasma corticosterone levels than the controls. In the brain of the experimental animals, dopaminergic activity appeared to be decreased, while serotonergic activity increased. Our results indicate that the prenatal treatment affected brain development in the offspring and as a consequence programmed the developing HPA axis in such a way as to hyperfunction under basal conditions, leading to its exhaustion and its inability to react properly to stress.

Adrenal Glands↗

Aging-related changes in IGF-II and c-fos gene expression in the rat brain.

The protein products of growth factor genes such as IGF-II and cellular oncogenes such as c-fos are believed to be necessary for the support of normal neuronal function. Steady-state levels of c-fos and IGF-II mRNA were determined in the brain of young and old rats, using Northern analysis. Both RNAs were found to be decreased in the brain of aged rats. Age-related decrease was detected in the hippocampus, hypothalamus, striatum, cerebral cortex and cerebellum, for IGF-II mRNA, and in the cerebral cortex and cerebellum for c-fos mRNA. Furthermore, changes in the degree and pattern of DNA methylation were noted at both gene loci, in the aged rat brain. Our results could reflect changes at the genomic level possibly related to the process of aging and the accompanying decline in brain function.

Aging↗

Differential expression of the insulin-like growth factor II and transthyretin genes in the developing rat choroid plexus.

Choroid plexus (CP) development may depend on an inductive interaction between primordial CP epithelium and the overlying mesenchyme. Expression of the two CP epithelial-expressed genes, transthyretin (TTR) and insulin-like growth factor II (IGF-II), were studied by in situ hybridization in the developing rat. Transthyretin mRNA is expressed in abundance in the primordial CP epithelium prior to CP morphogenesis (e10-11) but IGF-II mRNA expression begins later (e13) and increases gradually as morphogenesis proceeds. In the CP stroma (mesenchyme), IGF-II mRNA is abundant prior to CP morphogenesis but decreases as embryogenesis proceeds and is absent in the adult. Our findings suggest that IGF-II may play an early paracrine and later autocrine role in CP development. A model is proposed in which IGF-II synthesized by mesenchyme serves as an inducing principle for CP epithelial differentiation.

Animals↗

Hormonal control of insulin-like growth factor-II gene expression in the rat liver.

IGF-II in the rat is an embryonic/fetal growth factor. Transcription of its gene falls abruptly in the liver at about 18-20 days postnatally. In an attempt to elucidate the mechanisms controlling this phenomenon, we used Northern analysis to investigate the effect of corticosterone and thyroid hormones (tri-iodothyronine and tetra-iodothyronine) on hepatic IGF-II mRNA levels. The administration of either corticosterone or tri-iodothyronine to 8-day-old pups resulted in a significant decrease in IGF-II mRNA when the animals were examined on day 12 of life. Adrenalectomy, thyroidectomy or adrenalectomy combined with thyroidectomy were, however, without effect. Our results indicate that glucocorticoid and thyroid hormones are not the exclusive regulators of IGF-II gene transcription in the rat liver, but participate in this process, which appears to involve multifactorial interactions.

Animals↗

The effects of adrenalectomy and thermal stress on glutamic acid decarboxylase activity in different regions of the rat brain.

Glutamic acid decarboxylase (GAD) enzyme activity was measured in synaptosomes prepared from the hypothalamus, the hippocampus, the striatum and the cerebral cortex of control, adrenalectomized and rats exposed to a thermal stress. Adrenalectomy caused a statistically significant decrease in the enzyme activity in the striatum, while it had no effect in the other three brain areas. On the other hand, exposure to the thermal stress resulted in a dramatic increase of GAD specific activity in all brain areas examined. This thermal stress-induced increase in enzyme activity was observed in both non-operated and adrenalectomized animals, which implies that it is not mediated by glucocorticoids.

Adrenalectomy↗

Expression of IGF-I and IGF-II genes in the adult rat eye.

We have investigated the transcription of IGF-I and IGF-II genes in the adult rat eye. Each eye was dissected into cornea, lens, sclera + choroid + pigment epithelium, and neural retina. Total cellular RNA was isolated from each of these tissues. Northern blot analysis using rat coding region cDNA probes revealed the presence of IGF-I and IGF-II specific transcripts in the retina and the sclera but not in the lens and cornea. Retina demonstrated the highest level of IGF-I and IGF-II expression. Our results suggest autocrine and paracrine effects of the IGFs and their possible involvement in normal eye physiology as well as in the pathogenesis of certain eye diseases.

Animals↗

Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system.

The rat insulin-like growth factor II gene, encoding a fetal somatomedin, expresses a multitranscript family in embryonic/fetal tissues and in the adult brain and spinal cord. By performing in situ hybridization on tissue sections of adult brain and spinal cord, we have found that these transcripts are not expressed in neural or glial cells but are expressed in the epithelium of the choroid plexus of each cerebral ventricle and in the leptomeninges. We propose that the choroidal epithelial cells synthesize and secrete insulin-like growth factor II into the cerebrospinal fluid.

Animals↗

Pattern of the insulin-like growth factor II gene expression during rat embryogenesis.

The rat insulin-like growth factor II (IGF-II) gene, encoding a fetal somatomedin, expresses a family of transcripts in embryonic/fetal tissues, and also in the adult choroid plexus and the leptomeninges. We have localized IGF-II gene transcripts in sections of rat embryos of embryonic days 10-16 by performing in situ hybridization. These transcripts are present in the head mesenchyme, formed from both the mesoderm and the cephalic portion of the neural crest, and also in the majority of other tissues of mesodermal origin, predominantly those derived from the somites and the lateral mesoderm. Intense labelling was detected in muscle cells, and their precursors, throughout the examined stages, whereas in chondrocytes the initial high level of hybridization declined substantially prior to ossification. IGF-II gene transcripts are also present in derivatives of other germ layers, but in restricted sites. Thus, from the derivatives of the endoderm, only the liver and the bronchial epithelium yielded hybridization signals. Ectoderm-derived tissues, including the central and peripheral nervous system, were negative for hybridization, with the exception of the choroid plexus, the newly forming pituitary rudiment and, to a lesser extent, the auditory placode. The pattern of IGF-II gene expression during embryogenesis overlaps significantly with the reported distribution of immunohistochemically detected TGF-beta 1. A paracrine/autocrine role for IGF-II in the developmental process is discussed.

Animals↗

Effects of a prenatal androgen peak on rat brain sexual differentiation.

Exposure of the developing female brain to a 5 alpha-dihydrotestosterone surge on day 18 of gestation resulted in defeminization and slight masculinization of the brain. In contrast, abolition of the androgenic effects of the testosterone peak naturally occurring in male fetuses on day 18 of gestation by exposure of the developing male brain to cyproterone acetate, at that time, resulted in demasculinization while feminization was not affected. On the basis of these results, we suggest that both the prenatal testosterone peak and the high testosterone levels occurring in males neonatally are necessary for aromatization sufficient to effect complete male rat brain sexual differentiation.

Androgen Antagonists↗

Glucocorticoid receptors in developing rat brain and liver.

Dexamethasone receptors were measured by conventional equilibrium steroid binding studies in rat liver and brain cytosol, during late prenatal and postnatal development, Receptor binding could be detected in both cytosol preparations as early as the 17th day of gestation. Receptor levels in the cytosol from intact animals reached adult values by the 1st day after birth in both tissues. Using adrenalectomized animals an increase which reached adult values was observed during the first postnatal week for liver and the second postnatal week for brain. At physiological concentrations of endogenous glucocorticoids depletion of receptor from the cytosol of intact animals was minimal at postnatal day 1 and reached adult levels by day 7. Chromatographic analysis in DEAE-Sephadex A50 minicolumns of unactivated and activated receptor constituents revealed the same pattern as that of adult animals. Glucocorticoid receptor complex from developing liver and brain was shown to be capable of binding to isolated adult liver nuclei after in vitro activation. However full capacity, for nuclear binding was observed in vivo, after injection of inducing doses of [3H]dexamethasone: By the end of the first week after birth adult nuclear binding capacity was observed in experiments in vivo while values peaked during the second week, in both tissues studied.

Animals↗

The distribution and properties of the glucocorticoid receptor from rat brain and pituitary.

The distribution and properties of cytoplasmic binding sites for the synthetic glucocorticoid dexamethasone and the natural glucocorticoid corticosterone in the brain and the pituitary were studied in detail. Cortisol-17 beta acid, a derivative which does not bind to the glucocorticoid receptor but is a competitor of corticosterone binding to plasma, was used to overcome plasma interference. In vitro competition assays in the presence of excess cortisol acid reveal that dexamethasone is as effective a competitor for [3H]corticosterone binding as corticosterone itself. Scatchard analysis of equilibrium experiments with both steroids, using cytosol from various brain areas and from the pituitary yielded linear plots, suggesting one class of binding sites. The quantitative distribution of the sites follows the pattern: cortex greater than hippocampus greater than or equal to pituitary greater than hypothalamus greater than brain stem white matter. Furthermore, kinetic analysis of corticosterone dissociation showed a first order reaction, thus indicating the presence of one type of receptor in all brain areas examined. Rat brain cytosolic receptors for corticosterone and dexamethasone elute from DEAE-Sephadex A-50 anion exchange columns at 0.3 M NaCl in the presence of stabilizing sodium molybdate and at 0.15 M NaCl and/or in the buffer wash when heat-activated, thus exhibiting the characteristic activation pattern of rat liver cytosolic glucocorticoid receptor. The ratio of the buffer wash to the 0.15 M NaCl form is low for dexamethasone and very high for corticosterone. Receptor complexes from various brain parts showed the same activation pattern. In our experiments, brain corticosterone and dexamethasone receptors stabilized by sodium molybdate are indistinguishable by a number of techniques, thus indicating that it is unnecessary to evoke specific binding sites for each glucocorticoid.

Animals↗

Effect of maternal adrenocorticotropin injections on the differentiation of sexual behavior of the offspring.

Male and female rats were prenatally exposed to high levels of corticosteroids, by treatment of their mothers with ACTH, during the last third of pregnancy. In the females, treatment increased the ano-genital distance at birth, but no effect on sexual differentiation could be detected in the adult animals: They had normal cyclic reproductive function and female lordotic sexual behavior. The prenatal treatment demasculinized the males, who showed decreased ability for complete male copulatory behavior. The demasculinizing effect of prenatal corticosteroids was, however, particularly pronounced in certain litters, while not affecting others at all.

Adrenal Cortex Hormones↗

Neonatal neural organizing effects of exogenous corticosteroids on sexual differentiation of the brain in the female rat.

Testosterone, deoxycorticosterone, or vehicle was administered neonatally to female Long-Evans rats. Parameters expressing the reproductive physiology and behavior of the adult animals were studied. It was found that neonatal administration of testosterone produced the expected "defeminization" and "masculinization" of the brain, affecting both the reproductive behavior and cyclicity of these females. In contrast, neonatal administration of the adrenal steroid did not affect cyclicity although it "defeminized" and "masculinized" sexual behavior, albeit to a lesser degree than testosterone. The results suggest a dichotomy in the neuroregulation of reproductive physiology and sexual behavior.

Animals↗