Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways

Oestrogen (E2) plays significant roles in variety of biological events such as the development and maintenance of female reproductive organs, bone and lipid metabolisms. More recently, from study of knock-out mice deficient in oestrogen receptor (ER) alpha and ERbeta it turned out that normal spermatogenesis requires the E2 actions. Furthermore, this female steroid hormone is also well known to be deeply involved in many pathophysiological events such as osteoporosis and cancer development in female reproductive organs. It is particularly well known that most breast cancer is dependent on E2 in its development. Such E2 actions are thought to be mediated through two subtypes of ERs. Growth factors have been shown to synergize in this E2 signalling pathway, although the actual molecular mechanism largely remains unknown. Recently, we found that the MAP kinase activated by growth factors phosphorylates the Ser118 residue of the human ERalpha A/B domain and this phosphorylation potentiates the N-terminal transactivation function (AF-1) of human ERalpha, indicating the possible molecular mechanism of a novel cross-talk between E2 and growth factor signalling pathways. More recently, we have identified a coactivator associating with the hERalpha AF-1 in a MAPK-mediated phosphorylation-dependent manner. In this review, the molecular mechanism of this cross-talk is discussed in terms of the transactivation function of ERs, and their coactivators.     

Modulation of neuronal histamine in control of food intake

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.     

Comparison of thermosensitivity in the preoptic/anterior hypothalamic area and the midbrain of the rabbit

Summary To characterize the role of the midbrain temperature-sensitive structure in thermoregulation, the relative importance of thermosensitivity in the hypothalamus and the midbrain was studied in terms of heat production and heat loss in the rabbit. It was found that altering the local temperature in the midbrain had no influence at all on heat loss from the ear surface and also on heat production, while cooling and warming of the preoptic/anterior hypothalamic area induced appropriate thermoregulatory responses.     

Increase in O(2) delivery with hyperoxia does not increase O(2) uptake in tetanically contracting dog muscle

We investigated the influence of hyperoxia on O(2) uptake in tetanically contracting canine gastrocnemius. Hyperoxia showed neither increase in O(2) uptake nor decrease in lactate release, irrespective of increased O(2) supply, venous Po(2) and vascular resistance, as compared to normoxia, suggesting that hyperoxia decreases O(2) diffusion conductance and/or effective O(2) supply probably due to arteriovenous O(2) diffusion shunt.     

Histopathological classification of malignant lymphomas in slaughtered swine

A histological classification of 36 cases of malignant lymphoma in slaughtered swine is reported. All the lymphomas observed were diagnosed as diffuse types and were further classified into four types by their histological characteristics based on the classification of the Japanese Lymphoma Study Group (Suchi et al., 1979). The cases consisted of 16 of the Burkitt type, 2 of the immunoblastic type, 3 of the medium-sized cell type and 15 of the mixed cell type. The histological appearances of these lymphomas were compared with those of human lymphomas. All tumours closely resembled non-Hodgkin's diffuse type of B cell lymphoma and differed from tumours in other sites such as the liver and kidneys.     

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin > imipramine > desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verified that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.     

Extracorporeal circulation before and after ultrasonographic evaluation of the ascending aorta

BACKGROUND: To further gain insight into atheroembolization mechanisms epiaortic two-dimensional echocardiographic evaluation before extracorporeal circulation and after decannulation may be helpful. METHODS: Epiaortic two-dimensional echocardiography was performed before cannulation and after decannulation in 188 (124 men) patients (mean age, 67.7 years; range, 43 to 86 years) undergoing operation with extracorporeal circulation for ischemic heart disease during 1996. RESULTS: After decannulation, a new intimal lesion was recognized in 10 of 188 patients (5.3%): mobile type in 5 patients (3 ending with a stroke [60%], 2 having brain computed tomographic scans compatible with embolism), intimal tear in 2, and intimal irregularity in 3 patients. Stroke occurred in a significantly smaller number of patients (2 of 178 [1.1%]; p < 0.001) without new lesions. CONCLUSIONS: Clamp- or cannula-induced new lesions, especially of mobile type, are often complicated by postoperative stroke. Aggressive surgical technique modifications may need to be considered to avoid creating new lesions, particularly of the mobile type.     

Effects of bilateral jugular vein ligation on local cerebral blood flow

The authors examined the effect of bilateral jugular vein ligation (JVL) on local cerebral blood flow (CBF). Local CBF was measured in the neocortex of the frontal lobe over a 1-week period in 10 freely moving male rats. Measurements were taken with the hydrogen clearance method before and after the rat underwent either an operation of bilateral JVL or a sham operation. After the sham operation, blood flow values did not change significantly compared with preoperative values. Blood flow values decreased rapidly in rats with JVL. For 3 hours after surgery, JVL values were significantly lower (p <0.05) than preoperative values were, then gradually they recovered and reached preoperative values within 48 hours. Histopathologic study showed no remarkable parenchymal damages in the brain of rats with JVL. These results show that bilateral JVL produces a reversible decrease in the CBF and does not cause histopathologic brain damages.