bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Estradiol and Raloxifene Analog on Brain, Adrenal and Serum Allopregnanolone Content in Fertile and Ovariectomized Female Rats
Authors: Genazzani Andrea R. , Bernardi Francesca , Stomati Massimo , Monteleone Patrizia , Luisi Stefano , Rubino Silvia , Farzati Angelo , Casarosa Elena , Luisi Michele , Petraglia Felice 
Published: April 2003

Allopregnanolone is a neuroactive steroid synthesized in rat gonads, adrenal cortex, and central nervous system. It has been suggested that sex steroid hormones might influence allopregnanolone concentrations but no clear data have ever been reported. The aim of the present study was to investigate the effects of administration of 17β-estradiol (17β-E2), the raloxifene analog LY-117018 or their combination on allopregnanolone levels in fertile and ovariectomized (OVX) rats. Thirteen groups of 12 Wistar female rats each received either 17β-E2 (0.1 or 1 µg/day) or LY-117018 (25, 250, and 1,250 µg/day), or 17β-E2 1 µg/day plus LY-117018: 25, 250, and 1,250 µg/day for 14 days. The rats were then sacrificed and allopregnanolone content was assessed in the hypothalamus, hippocampus, pituitary, adrenals, and serum. Ovariectomy determined a significant decrease in allopregnanolone content in the hypothalamus, hippocampus, pituitary, and serum, while increasing it in the adrenals (p < 0.01). In OVX rats, the administration of either 17β-E2 or LY- 117018 restored ovariectomy-induced allopregnanolone changes. The administration of LY-117018 in addition to 17β-E2 to OVX animals suppressed the increase in allopregnanolone levels determined by 17β-E2 in the hippocampus, hypothalamus, and pituitary, but not in the adrenals and serum. In fertile rats, the administration of LY-117018 reproduced the effects of ovariectomy. This study shows that the raloxifene analog LY-117018 has an estrogen-like action on the central nervous system of OVX rats when administered alone, while it acts as an antiestrogen in the presence of 17β-E2, both in OVX animals treated with 17β-E2 and in fertile rats. A different effect was observed in the adrenal glands. The mechanism of action of this compound has still to be clarified.
Effect of Oxidative Stress on the Uptake of GABA and Glutamate in Synaptosomes Isolated from Diabetic Rat Brain
Authors: Duarte Ana , Santos Maria , Seiça Raquel , Resende de Oliveira Catarina 
Published: April 2003

It has been suggested that increased oxidative stress might be involved in the pathophysiology of diabetic complications. In this study, we investigated the effect of diabetes on the susceptibility of synaptosomes to oxidative stress (induced by the oxidizing pair ascorbate/Fe<sup>2+</sup>) and on the uptake of the amino acid neurotransmitters γ-aminobutyric acid (GABA) and glutamate. We found a lower susceptibility of synaptosomes isolated from Goto-Kakizaki (GK) rats, a model of non-insulin-dependent diabetes mellitus, to lipid peroxidation as compared with synaptosomes isolated from Wistar control rats (6.40 ± 1.05 and 12.14 ± 1.46 nmol thiobarbituric acid reactive substance/mg protein, respectively). The lower susceptibility of GK rat synaptosomes to membrane lipid peroxidation correlates with an increase in synaptosomal vitamin E levels (835 ± 58.04 and 624.26 ± 50.26 pmol/mg protein in diabetic and normal rats, respectively). In the absence of ascorbate/Fe<sup>2+</sup>, no significant differences were observed between the levels of lipid peroxidation of synaptosomes isolated from diabetic and normal rats. Studies of neurotransmitter uptake show that the [<sup>3</sup>H]glutamate uptake was decreased by about 30% in diabetic GK rats as compared with control Wistar rats, whereas the [<sup>3</sup>H]GABA uptake was not significantly different from controls. Under oxidizing conditions, the glutamate uptake in diabetic rats was unaffected, and a decreased GABA uptake (41.39 ± 4.41 and 60.96 ± 6.4% of control in GK and Wistar rats, respectively) was observed. We conclude that the increased resistance to oxidative stress in GK rat synaptosomes may be due to the increased vitamin E content and that diabetic state and oxidative stress conditions differentially affected the uptake of the neurotransmitters GABA and glutamate.
Effects of Photoperiod and Ambient Temperature on the Gonadotropin-Releasing Hormone Neuronal System in the Gray Hamster, <i>Tscherskia triton</i>
Authors: Kawamoto Keiichi , Tanaka Susumu , Kawano Masako , Hayashi Toshiyuki , Tsuchiya Kimiyuki 
Published: April 2003

In seasonal breeders like the hamster, gonadal function depends on the photoperiod. The present study examined the effects of different photoperiods and ambient temperatures on the gonadotropin-releasing hormone (GnRH) neuronal system in male gray hamsters, <i>Tscherskia triton</i>. Hamsters were kept from birth under a long-day (LD: 16 h light and 8 h dark) photoperiod and at 23°C until the experiment began. The animals were then kept for 30 days under different photoperiods and ambient temperatures. After autopsy, immunocytochemical and semiquantitative reverse transcription-polymerase chain reaction analyses were performed on the hamster forebrain. Exposure to a short-day (SD: 8 h light and 16 h dark) photoperiod at 23°C induced a functional decline in the GnRH neuronal system (increased neuron number and immunoreactivity, and reduced cell size). LD with low ambient temperature (7°C) did not influence the GnRH neuronal system. In contrast, SD with low ambient temperature enhanced the SD-induced functional decline in GnRH neurons. Changes in immunoreactivity of GnRH fibers in the median eminence, their release site, were also similar to those in neuronal perikarya. Significant differences in GnRH gene expression were detected in the SD only group and the SD with low ambient temperature group. However, no differences were detected between the two groups. These findings suggest that low ambient temperature enhanced the SD-induced decline in GnRH release from nerve terminals, but was not a crucial factor in the synthesis of this decapeptide.
Food Intake-Induced Leptin Secretion Modulates Hypothalamo-Pituitary-Adrenal Axis Response and Hypothalamic Ob-Rb Expression to Insulin Administration
Authors: Giovambattista Andrés , Chisari Andrea N. , Gaillard Rolf C. , Spinedi Eduardo 
Published: April 2003

The mutation of the <i>ob</i> gene is known to induce a phenotype of obesity accompanied by symptoms including enhanced production of glucocorticoid. Chronic administration to <i>ob/ob</i> mice of leptin, the <i>ob</i> gene product, reverses hypercorticosteronemia. This establishes a clear relation between adipocyte and hypothalamo-pituitary-adrenal (HPA) axis functions. In the present study we investigated the acute modulatory effects of food intake-stimulated leptin secretion on HPA axis activity and hypothalamic leptin receptor (Ob-Rb) expression in 24-hour fasting, adult female, BALB/c mice after insulin-induced hypoglycemia. Our results indicate that: (1) food supply for 45 min to 24-hour fasting mice increased plasma glucose levels and reversed both hypercorticosteronemia and hypoleptinemia; (2) the insulin-induced hypoglycemia produced a marked HPA axis activation in animals with no access to food but this response was fully prevented by food intake and the consecutive increase in plasma leptin levels; (3) the inhibitory effect of leptin on the HPA axis response to insulin-induced hypoglycemia was corroborated by i.p. administration of murine leptin, and (4) fasting-induced hypothalamic Ob-Rb overexpression is not modulated by insulin itself but by leptin, since increase in leptin levels by food intake or by administration of exogenous leptin completely reversed this Ob-Rb overexpression. These results confirm the inhibitory effect of leptin on the HPA axis response to various stress stimuli. They clearly demonstrate that acute food intake in 24-hour fasting mice: (a) rapidly reduced fasting-induced hypercorticosteronemia by enhancing both spontaneous and insulin-elicited endogenous leptin secretion; (b) fully prevented HPA axis response to insulin administration, by rapidly increasing endogenous leptin secretion and probably also by diminishing the extent and the duration of insulin-induced hypoglycemia, and (c) abolished hypothalamic Ob-Rb overexpression induced by fasting itself combined with insulin treatment. The present data strongly suggests an inhibitory effect of endogenous leptin on insulin-induced HPA axis response, an interaction relevant to the physiological adaptation to starvation and caloric excess, and further supports the pivotal role played by the hypothalamus in restoring homeostasis in different allostatic states.
Dopaminergic Input to the Ventromedial Hypothalamus Facilitates the Oestrogen-Induced Luteinizing Hormone Surge in Ewes
Authors: Anderson Stephen T. , Walsh John P. , Tillet Yves , Clarke Iain J. , Curlewis Jonathan D. 
Published: April 2003

In this study we examined the release of dopamine and noradrenaline in the ventromedial hypothalamus (VMH) of ovariectomized ewes during the oestrogen-induced luteinizing hormone (LH) surge by measuring their respective metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and methoxyhydroxyphenylglycol (MHPG) using microdialysis. Further we investigated whether inhibition of catecholamine synthesis in the VMH by bilateral reverse dialysis of α-methyl-<i>p</i>-tyrosine (α-MPT) would block the oestrogen-induced LH and/or prolactin surges. Oestradiol treatment (50 µg oestradiol benzoate) of ovariectomized ewes resulted in a biphasic LH response, significantly (p < 0.05) decreasing LH concentrations from 2.5 to 10.5 h after injection, followed by an LH surge beginning at 16 h. Prolactin concentrations were also significantly (p < 0.05) increased in oestradiol-treated ewes from 13 h. VMH DOPAC concentrations in oil-vehicle-treated animals were at the level of detection (0.02 ng/ml) in most samples over the 24-hour sampling period. In oestradiol-treated ewes, VMH DOPAC levels were initially low before and up to 8 h after oestradiol injection but then increased significantly (p < 0.05) at 10–12 h and remained elevated up to 20 h after injection. In contrast, oestradiol injection had no effect on MHPG concentrations in the VMH. Bilateral reverse microdialysis of α-MPT into the VMH significantly (p < 0.05) delayed the time from oestradiol injection to the onset of the LH surge, the time to peak LH concentration and attenuated the LH surge compared with reverse dialysis of Ringer solution alone. In contrast, α-MPT treatment had no effect upon the oestradiol-induced increase in prolactin concentrations. This study provides evidence that the VMH is an important hypothalamic site in the neuro-endocrine control of the LH surge in ewes. The results suggest that dopaminergic neurons with terminals in the VMH are part of a neuronal pathway mediating the positive feedback effects of oestradiol on gonadotropin-releasing hormone secretion and the LH surge.
Estrogens Act in Rat Hippocampus and Frontal Cortex to Produce Rapid, Receptor-Mediated Decreases in Serotonin 5-HT<sub>1A</sub> Receptor Function
Authors: Mize Amy L. , Poisner Alan M. , Alper Richard H. 
Published: April 2003

Previously our laboratory has shown that 17β-estradiol in vivo rapidly decreases R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding (a measure of the initial biochemical event in the intracellular signaling pathway associated with 5-HT<sub>1A</sub> receptors) in the hippocampus, frontal cortex and amygdala. Studies were designed to determine if 17β-estradiol also acts in vitro on estrogen receptors in the hippocampus and frontal cortex to decrease 5-HT<sub>1A</sub> receptor function. Hippocampus and frontal cortex were dissected from ovariectomized rats and incubated for up to 3 h with various estrogens and antiestrogens; membrane homogenates were prepared for R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding assays. 17β-Estradiol (10<sup>–6</sup> <i>M</i>) decreased the maximal response in the R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding assay in a time-dependent manner (observed at 30, 60 and 120 min) in both hippocampus and frontal cortex. The hormone, however, did not alter the EC<sub>50</sub> of R(+)-8-OH-DPAT. When hippocampus and frontal cortex were incubated in graded concentrations of 17β-estradiol for 1 h, the calculated EC<sub>50</sub> was approximately 2.5 × 10<sup>–8</sup> <i>M</i> in both brain regions. The nonestradiol estrogen diethylstilbestrol also decreased 5-HT<sub>1A</sub> receptor function while the less potent estrogens 17α-estradiol and estriol were inactive at 5 × 10<sup>–8</sup> <i>M</i>. The estrogen receptor antagonist ICI 182,780 potently and completely blocked the effects of 17β-estradiol on 5-HT<sub>1A</sub> receptor function with an apparent K<sub>B</sub> of approximately 10<sup>–9</sup> <i>M</i>. These data demonstrate clearly that estrogens can act on estrogen receptors located in hippocampus and frontal cortex of ovariectomized rats to produce rapid heterologous decreases in 5-HT<sub>1A</sub> receptor function.
Expression of Corticotropin-Releasing Hormone Type 1 Receptor in Paraventricular Nucleus after Acute Stress
Authors: Imaki Toshihiro , Katsumata Harumi , Miyata Mariko , Naruse Mitsuhide , Imaki Junko , Minami Shiro 
Published: April 2003

We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular nucleus (PVN) that express CRH type 1 receptor (CRH-R1) following stress. We also conducted immunohistochemistry to determine whether CRH-R1 mRNA was translated to CRH-R1 protein in the PVN. Thirty-minute restraint stress given to male Wistar rats increased c-<i>fos</i> mRNA expression primarily in the CRH-producing neurons of the parvocellular PVN. Small numbers of vasopressin and oxytoxin-producing cells were also labeled by c-<i>fos</i> probes. Approximately 70% of CRH-R1 positive neurons exhibited CRH mRNA 2 h after the beginning of stress, while only a small percentage of the vasopressin and oxytocin-producing cells coexpressed CRH-R1 mRNA. CRH-R1 immunoreactivity, which was detected in the perikarya and fibers of PVN neurons, appeared to increase in response to stress, though this was not statistically significant. Pretreatment with a selective CRH-R1 antagonist, CP-154,526, significantly attenuated stress-induced corticotropin (ACTH) secretion as well as c-<i>fos</i> mRNA expression in the PVN. These results demonstrate that acute stress increases neuronal activation and CRH-R1 mRNA expression primarily in CRH-producing neurons of the parvocellular PVN, that CRH-R1 message is translated to CRH-R1 protein, and that PVN neurons are activated at least in part through CRH-R1 under acute stress. The data further support the possibility of feedback regulation of CRH itself in CRH-producing neurons.
The Endocrine Disrupters Butyl Benzyl Phthalate and Bisphenol A Increase the Expression of Progesterone Receptor Messenger Ribonucleic Acid in the Preoptic Area of Adult Ovariectomized Rats
Authors: Funabashi Toshiya , Kawaguchi Maiko , Kimura Fukuko 
Published: April 2003

Butyl benzyl phthalate (BBP) and bisphenol A (BPA), so-called endocrine disrupters, are known to mimic the action of estrogens: they are thus liable to influence reproductive functions. Since little is known about their action on gene expression in the adult hypothalamus, we examined the effects of these chemicals on the expression of estrogen-regulated mRNAs, i.e., progesterone receptor (PR) mRNA, preproenkephalin (PPE) mRNA and neurotensin (NT) mRNA, in the hypothalamus and pituitary of adult female rats. Two weeks after ovariectomy, rats were subcutaneously injected with 10 mg BBP, 10 mg BPA, or 10 µg 17β-estradiol (E<sub>2</sub>) in sesame oil, or with sesame oil alone as a control. Twenty-four hours after the injection, tissues including the preoptic area (POA), mediobasal hypothalamus (MBH) and anterior pituitary were collected. Northern blot revealed that injection of E<sub>2</sub> resulted in expected changes, i.e., significant increases in PR mRNA in the POA, MBH and anterior pituitary, and in PPE mRNA in the MBH. We also found that injection of BPA significantly increased PR mRNA in the POA and anterior pituitary, while injection of BBP increased PR mRNA in the POA and anterior pituitary, although the increase in the anterior pituitary was not significant. No significant effect of E<sub>2</sub>, BPA, or BBP on NT mRNA in the POA was detected. The present study demonstrates that the two endocrine disrupters BPA and BBP can increase the expression of PR mRNA in the POA of adult ovariectomized rats.
Acute Effects of Purified and UV-Inactivated Herpes simplex Virus Type 1 on the Hypothalamo-Pituitary-Adrenocortical Axis
Authors: Ben-Hur Tamir , Cialic Ron , Itzik Anna , Yirmiya Raz , Weidenfeld Joseph 
Published: April 2003

Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. We have previously demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA) axis activation. In this study we characterized the acute effects of HSV-1 on the HPA axis occurring before viral replication and appearance of clinical signs of encephalitis. Since in previous studies we used crude virus preparations which may contain immune factors produced by the infected cells, we tested here the effects of purified HSV-1 virions. HSV-1 was propagated on Vero cells and virions were purified by centrifugation in sucrose gradients. Inactivation of viral infectivity was achieved by UV-irradiation, which caused a million-fold decrease in virus titer, as determined by plaque assay. Intracerebroventricular (ICV) inoculation of crude or purified virions induced a dose dependent increase in serum corticosterone and corticotropin (ACTH). This effect was maximal within 3.5 h postinfection and lasted for 72 h. ICV inoculation of UV-inactivated purified virions caused a marked increase in serum corticosterone and ACTH at 3.5 h, but in contrast to the effect of the active virus, the hormone levels gradually decreased at 24 h, and returned to basal levels at 72 h postinfection. HSV-1-induced HPA axis activation at 3.5 h was completely abolished by pretreatment with interleukin-1 receptor antagonist, injected ICV. Adrenalectomized rats failed to respond to ICV inoculation of purified HSV-1 by increase in ACTH. In contrast, these rats responded to ICV injection of LPS. In conclusion: (1) HSV-1 can acutely activate the HPA axis before and independently of any viral replication; (2) HSV-1-induced HPA axis activation depends on a permissive action of circulating glucocorticoids and on host derived brain interleukin-1.
Changes in Fos Expression in Various Brain Regions during Deoxycorticosterone Acetate Treatment: Relation to Salt Appetite, Vasopressin mRNA and the Mineralocorticoid Receptor
Authors: Pietranera Luciana , Saravia Flavia E. , McEwen Bruce S. , Lucas Louis L. , Johnson Alan Kim , De Nicola Alejandro F. 
Published: April 2003

Salt appetite, a conditioning factor for hypertension and cardiovascular diseases, is produced when high doses of mineralocorticoids are given to experimental animals. A commonly used procedure to identify neuronal activation is to determine the number of Fos-immunoreactive cells. In rats with established salt appetite after 8 days of deoxycorticosterone acetate (DOCA) treatment, Fos-positive cells were studied in seven brain areas. Significant increases in Fos activity were recorded in the paraventricular (PVN) and supraoptic (SON) nuclei, median preoptic nucleus (MnPO), organum vasculosum of the lamina terminalis (OVLT), preoptic area (POA), bed nucleus of the stria terminalis (BNST) and amygdala (AMYG). In most of these areas, increased Fos expression was also observed early (2 h) after a single DOCA injection, well before salt appetite develops. Using a mineralocorticoid receptor (MR) antibody, we studied whether Fos-active regions also expressed MR. MR-positive cells were found in the OVLT, MnPO, AMYG and BNST, but not in the POA, PVN and SON. In the PVN and SON, nevertheless, prolonged or single DOCA treatment increased expression of mRNA for arginine vasopressin (AVP). The present demonstration of Fos activation, in conjunction with differential expression of MR and stimulation of AVP mRNA, suggests that a neuroanatomical pathway comprising the AMYG, osmosensitive brain regions and magnocellular nuclei becomes activated during DOCA effects on salt appetite. It is recognized, however, that DOCA effects may also depend on mechanisms and brain structures other than those considered in the present investigation. Since some Fos-positive regions were devoid of MR, a comprehensive view of DOCA-induced salt appetite should consider nongenomic pathways of steroid action, including the role of reduced DOC metabolites binding to GABAergic membrane receptors.
Association between Blood Pressure and Cognitive Function in a Biracial Community Population of Older Persons
Authors: Morris Martha Clare , Scherr Paul A. , Hebert Liesi E. , Bennett David A. , Wilson Robert S. , Glynn Robert J. , Evans Denis A. 
Published: April 2003

We examined whether or not blood pressure is related to cognitive function in a cross-sectional study of a biracial community of 5,816 persons aged 65 years and older. Blood pressure had a curvilinear association with cognitive performance in linear regression models adjusted for age, sex, race and education. Scores were lower by 2–5 percentiles at 100 mm Hg systolic pressure compared to scores at the mean of 140 mm Hg and lower by <1 percentile at 180 mm Hg. For diastolic pressure, scores were lower by 2–3 percentiles at 60 mm Hg and by 1–2 percentiles at 100 mm Hg compared to scores at the mean (77 mm Hg). The differences in the scores with low blood pressure were reduced with further adjustment for body mass index, self-perceived health status, depressive symptoms, alcohol use and smoking. The curvilinear associations were stronger among persons with histories of stroke, myocardial infarction and hypertension. The cross-sectional association between blood pressure and cognitive functions is small and curvilinear and more apparent in persons with cardiovascular conditions.
The Effects of Diazepam on Sleep Spindles: A Qualitative and Quantitative Analysis
Authors: Suetsugi Masatomo , Mizuki Yasushi , Ushijima Itsuko , Kobayashi Takayoshi , Watanabe Yoshifumi 
Published: April 2003

The effects of 2.5 or 5 mg diazepam (DIZ) on the sleep spindles were studied in 12 healthy male subjects. Polygraphic recordings and the state anxiety scale of the State Trait Anxiety Inventory (STAI) were made for 6 consecutive nights. An inert placebo was given on the first 3 nights and on the sixth night, and DIZ was administered on the fourth and fifth nights. DIZ produced increases in the amount of the slow and fast spindles in a dose-dependent manner. DIZ dose-dependently lowered the frequency of the fast spindles and elevated that of the slow spindles. Furthermore, the influence of DIZ on fast spindles was greater than that on slow spindles. DIZ decreased the state anxiety of the subjects in a dose-dependent manner. These results suggest that measuring the amount and the frequency of fast spindles could be a useful tool in predicting the anxiolytic effects of benzodiazepines.