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Biomedical subjects

T Shibasaki

Publications and source records attributed to T Shibasaki.

At least 217 records · Page 12Linked to original sources
PubMed1985

Effect of hypothalamic ventromedial lesions on plasma growth hormone response to growth hormone-releasing factor in rats.

The effect of ventromedial-arcuate (VMH-ARC) nuclei lesions on plasma growth hormone (GH) response to human growth hormone-releasing factor (GRF, 1 microgram/kg b.wt., i.v.) was studied in conscious rats after they had received chlorpromazine (CPZ) or CPZ plus antiserum against somatostatin (ASS). When rats were pretreated with CPZ alone, there was no difference in basal plasma GH level between VMH-ARC lesioned rats and controls. The magnitude of plasma GH response to GRF in 5 out of 6 VMH-ARC lesioned rats exceeded that of controls. When the same observation was repeated using the same rats after they had received ASS and CPZ, basal plasma GH levels of controls were significantly higher than those of VMH-ARC lesioned rats, and the magnitude of the plasma GH response to GRF was augmented in both groups of rats. The plasma GH response to GRF was comparable between two groups, though the peak plasma GH response to GRF was slightly but significantly lower in VMH-ARC lesioned rats as compared to controls. Pituitary GH content was reduced significantly in VMH-ARC lesioned rats as compared to controls. The results demonstrate that the pituitary responsiveness to GRF does not appear to be altered significantly in rats bearing bilateral VMH-ARC lesions. In addition, the placement of electrolytic lesions in VMH-ARC regions causes reduced SS secretion into the hypophyseal portal vessels and leads to an augmentation of plasma GH response to GRF.

Animals↗
PubMed1985

The satiety effect of growth hormone-releasing factor in rats.

The effect of growth hormone-releasing factor (GRF) on feeding behavior in rats was examined. Starvation-induced feeding was suppressed by intraventricular administration of 1 nmol and 4 nmol of synthetic human GRF (hGRF). Food intake was not affected when the peptide was administered by intraperitoneal injection. Furthermore, centrally administered hGRF also suppressed feeding in hypophysectomized rats. These results suggest that GRF suppression of food intake is mediated through the central nervous system independent of its effect on pituitary growth hormone secretion.

Animals↗
PubMed1985

The descending alpha-MSHergic (alpha-melanocyte-stimulating hormone-ergic) projections from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord in the rat.

Neuronal pathways containing alpha-melanocyte-stimulating hormone (alpha-MSH) extending from the zona incerta and lateral hypothalamic area to the inferior colliculus and spinal cord were analyzed using both immunohistochemical localization and a retrograde tracer. Biotinized horseradish peroxidase injected into the inferior colliculus or the thoracic cord of the rat labeled a number of neurons in the zona incerta and lateral hypothalamic area. Simultaneous immunostaining of the same sections with alpha-MSH antiserum showed that some of these neurons are alpha-MSHergic.

Animals↗
PubMed1985

Effect of dopamine, bombesin and cysteamine hydrochloride on plasma growth hormone response to synthetic growth hormone-releasing factor in rats.

In urethane anesthetized rats, an intracerebroventricular (icv) injection of 2 micrograms bombesin 5 min prior to the administration of synthetic human growth hormone-releasing factor (GRF) (1 microgram/kg, iv) inhibited plasma growth hormone (GH) response, while cysteamine hydrochloride (90 mg/kg, sc) administered 150 min beforehand depleted immunoreactive somatostatin content in the pituitary-stalk median eminence and consequently potentiated the response to GRF. Under the same experimental conditions, central injection of 1.89 micrograms (10(-8)M) dopamine hydrochloride or iv administration of L-DOPA (10 mg/kg) did not influence the subsequent plasma GH response to GRF. Results suggest indirectly that bombesin and cysteamine, but not dopamine, predominantly modulate somatostatin release from the hypothalamus.

Animals↗
PubMed1985

Presence of corticotropin-releasing factor-like immunoreactivity in human tumors.

Corticotropin-releasing factor (CRF)-like immunoreactivity was measured by radioimmunoassay in human organs and tumors associated with and without ectopic adrenocorticotropic hormone (ACTH) syndrome. It was found to be distributed widely in the stomach, pancreas, adrenal gland, and various tumors (e.g., medullary thyroid carcinoma, small cell carcinoma of the lung, pheochromocytoma, and adenocarcinoma of the gastrointestinal tract and pancreas) in a concentration less than one tenth of that of the hypothalamus. Dilution curves of CRF-like immunoreactivity in tissue extracts paralleled that of synthetic rat (human) CRF. Sephadex G-50 gel filtration showed that a major CRF-like immunoreactivity in tissue extracts coeluted with synthetic rat (human) CRF. Results suggest that a material(s) closely related immunologically to CRF is present widely in normal and tumor tissues outside of the central nervous system.

ACTH Syndrome, Ectopic↗
PubMed1985

CRF-containing neurons of the rat hypothalamus.

The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 micrograms/5 microliters/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus. The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.

Adrenalectomy↗
PubMed1985

Ontogenetic appearance of immunoreactive GRF-containing neurons in the rat hypothalamus.

Ontogenetic development of GRF-containing neurons in the rat hypothalamus was studied employing antisera which were generated against hpGRF (1-44)NH2 and rhGRF(1-43)OH: anti-hpGRF-C and -rhGRF sera recognize the species-specific C-terminal portions of the peptides, and anti-hpGRF-MC and -N sera recognize hpGRF(27-44)NH2 and the N-terminal portion of hpGRF(1-44)NH2, respectively. The anti-hpGRF-C and -rhGRF sera stained different neuronal cell bodies, which were localized in distinct hypothalamic areas. The former serum did not stain the axonal terminals in the median eminence, but the latter stained them strongly. The anti-hpGRF-MC and -N sera stained neuronal cell bodies, some of which corresponded to those immunolabelled with anti-hpGRF-C or -rhGRF serum. The anti-rhGRF serum first demonstrated immunoreactive perikarya in the ventral-lateral border of the arcuate nucleus of 19.5-day-old fetuses that had received an intraventricular colchicine administration 24 h previously. The immunoreactive fibers were recognized first in the external layer of the median eminence of untreated fetuses on day 19.5 of gestation, and then they increased in amount with development. No immunoreactive fibers, however, were found in the median eminence of colchicine-treated animals during the fetal period. It is concluded that in rats GRF may be synthesized in the perikarya on day 18.5 of gestation and conveyed to the median eminence without delay via axonal flow.

Aging↗
PubMed1985

Properties of adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells.

A class of K channels in cardiac muscle is reversibly blocked by intracellular adenosine 5'-triphosphate (ATP). The characteristics of this K channel were studied by recording single-channel currents in ventricular cells isolated enzymatically from guinea-pig heart. The reversal potential of single-channel currents agreed well with the K equilibrium potential. Blockers of other K channels, such as tetraethylammonium and 4-aminopyridine, decreased the mean open time of the channel. The chord conductance increased as the 0.24th power of the K concentration on the outer surface of the membrane, and showed a marked inward-going rectification on strong depolarizations. The degree of rectification was larger with increasing Na concentration on the inner side of the membrane. The kinetics of the channel were almost voltage independent, but depended on the concentration of intracellular ATP. The conductance of the channel was not affected by ATP. When channel kinetics were examined in the presence of ATP, the distribution of open times and closed times was fitted well with a sum of two exponential components. When ATP concentration was increased, the time constants obtained from the open-time histogram decreased and those from the closed-time histogram increased, resulting in a decrease of the open-state probability. The channel was blocked by ATP, adenosine 5'-diphosphate,5'-adenylylimidodiphosphate, guanosine 5'-triphosphate and uridine 5'-triphosphate, but not by adenosine 5'-monophosphate, creatine phosphate, creatine or adenosine. Plots of the open-state probability versus the ATP concentration revealed Michaelis-Menten saturation kinetics with strong co-operativity of multiple receptor sites (Hill coefficient 3-4, concentration of half-saturation 0.5 mM). It was concluded that this K channel has three or four receptor sites selective for triphosphate nucleotide on the inner surface of the membrane, and that the channel is blocked through the binding of agonists to the receptors.

4-Aminopyridine↗
PubMed1985

Membrane current through adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells.

The question whether activation of the ATP-regulated K channel is responsible for macroscopic anoxia-induced outward currents was examined in ventricular cells isolated enzymatically from guinea-pig heart. Gigaseal patch-clamp electrodes were used for a whole-cell voltage clamp. Membrane currents were compared in the same cell while the cell interior was dialysed by perfusing the electrode with different solutions. When the cell was dialysed with various ATP-deficient (less than or equal to 2 mM) internal solutions, the Ca current decreased in a dose-dependent manner to less than 10% of control at 0.5 mM-ATP. A slight (ca. 25%) decrease of the slope conductance for hyperpolarizing current was observed. When a delayed rectification on depolarization followed by a marked outward current tail on repolarization was present under control conditions, this time-dependent outward current was also depressed. An increase in a time-independent outward current was observed accompanied by marked current fluctuations. The outward current showed a reversal potential near the K equilibrium potential, inward rectification, and no relaxation on voltage jumps. The power density spectrum of the current fluctuations showed a pattern similar to the spectrum calculated from the single-channel currents of ATP-regulated K channels. The amplitude of the single-channel current, estimated from the fluctuations, was almost equal to that of the single-channel current. The total number of channels within one cell was estimated as 2000-3000. It is concluded that the ATP-regulated K channels are responsible for the increase in the outward current and the shortening of the action potential duration under various anoxic conditions.

Action Potentials↗
PubMed1985

Plasma growth hormone response to human growth hormone releasing factor in rats administered with chlorpromazine and antiserum against somatostatin. Effects of hypo- and hyperthyroidism.

The effect of hypo- and hyperthyroidism on the plasma growth hormone (GH) response to synthetic human growth hormone releasing factor (GRF) was determined in conscious, freely moving rats pretreated with chlorpromazine and antiserum against somatostatin. Chlorpromazine plus somatostatin antiserum pretreated rats gave consistent response to GRF which was not observed in untreated rats. Chlorpromazine alone has no effect on GH secretion induced by GRF in rat pituitary monolayer culture. In rats made hypothyroid by thyroidectomy, both basal and peak plasma GH responses to a small (0.25 microgram/kg bw) and a moderate dose of GRF (1 microgram/kg bw) were significantly reduced as compared to controls. In rats made hyperthyroid by the administration of thyroxine, basal and peak plasma GH responses to a small but not to a moderate dose of GRF were significantly reduced as compared to controls. A reduced plasma GH response to a small dose of GRF was observed 8 days after the cessation of thyroxine administration. The pituitary GH reserve was markedly reduced in hypothyroid but not in hyperthyroid rats as compared to their respective controls. These results indicate that plasma GH response to GRF is reduced both in hypo- and hyperthyroidism. The mechanism involved in the phenomenon appears to be different between the two conditions.

Animals↗
PubMed1985

The effect of free fatty acids on growth hormone (GH)-releasing hormone-mediated GH secretion in man.

The effect of FFA on GH-releasing hormone (GHRH)-mediated secretion of GH was examined in six normal young men. Three of the men were infused with 250 ml of a lipid-heparin solution at 1.67 ml/min for 150 min, and the other three were given an equivalent volume of saline in the same manner. Thirty minutes after the start of infusion, 100 micrograms GHRH (the 44-amino acid form) were injected iv, and plasma GH and FFA were measured. One week later, the same men participated in an identical experiment, but the ones who had received lipid-heparin previously were given saline and vice versa. In both experiments, plasma FFA increased to 2.25 +/- 0.16 meq/liter (mean +/- SEM) 60 min after the start of lipid-heparin infusion, whereas FFA levels did not change significantly in the saline-treated group. Mean plasma GH levels reached peak concentrations in both groups 30 min after GHRH treatment. However, the peak GH response when lipid-heparin was given was significantly diminished (8.4 +/- 1.7 ng/ml), compared with the peak response when saline was given (28.9 +/- 7.1 ng/ml). These data suggest that plasma FFA elevations induced by lipid-heparin infusion inhibit GH secretion induced by GHRH.

Adult↗
PubMed1985

The effect of glucose on growth hormone (GH)-releasing hormone-mediated GH secretion in man.

The effect of glucose on GH-releasing hormone (GHRH)-mediated GH secretion was examined in six normal young men. In two paired experiments, the six men drank a 75-g glucose solution or an equal volume of water 30 min before receiving, iv, 100 micrograms of the 44-amino acid form of human pancreatic GHRH (hGHRH-44). One week later, the same men underwent an identical experimental protocol in a cross-over trial. Basal plasma GH concentrations before hGHRH-44 administration were not statistically different in the two experiments [glucose experiment, 2.1 +/- 0.1 (+/- SE) ng/ml; water experiment, 2.6 +/- 0.6 ng/ml]. The mean peak plasma GH level occurred 30 min after hGHRH-44 administration in both experiments. However, the mean GH response was significantly diminished when the men received glucose (8.12 +/- 1.12 ng/ml) compared to that when they received only water (23.70 +/- 8.46 ng/ml; P less than 0.01). Thus, hyperglycemia may exert an inhibitory effect on the plasma GH response to hGHRH-44.

Adult↗
PubMed1985

Plasma GH responses to GHRH and insulin-induced hypoglycemia in man.

Changes in plasma GH levels in response to an intravenous bolus injection of 200 micrograms GHRH-44 or 0.1 U/kg body weight regular insulin were examined in normal men who were pre-treated with 200 micrograms GHRH-44 or 0.1 U/kg body weight regular insulin 120 min in advance. The prior bolus injection of GHRH-44 inhibited the plasma GH response to the subsequent administration of GHRH-44 whereas the plasma GH response to the subsequent injection of insulin was not influenced by the prior administration of GHRH-44. The prior administration of insulin attenuated the plasma GH response to the subsequently given GHRH-44. These results suggest that desensitization of GHRH receptors in somatotrophs and/or somatostatin hypersecretion induced by increase in plasma GH levels following the prior GHRH-44 administration may be involved in the mechanism by which the prior GHRH-44 administration or insulin-induced hypoglycemia suppressed plasma GH responses to the following GHRH-44 administration. Sudden suppression of somatostatin secretion, which causes rebound of GH secretion, may occur in insulin-induced hypoglycemia.

Adult↗
PubMed1985

The use of the corticotropin-releasing hormone test to monitor the recovery of patients with Cushing's disease or Cushing's syndrome due to an adrenal adenoma after adenomectomy.

Six patients with Cushing's disease and three with Cushing's syndrome due to an adrenal adenoma were monitored after their adenomectomy with the corticotropin-releasing hormone test to evaluate the progress of recovery of their pituitary adrenal function. Before surgery the patients with Cushing's disease showed either high, normal or low responses of plasma ACTH and cortisol to 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) administered intravenously, whereas all three patients with Cushing's syndrome due to an adrenal adenoma showed no response of plasma ACTH or cortisol to CRH. One or two months after surgery, the patients who had Cushing's disease had low levels of basal plasma ACTH and cortisol and their responses to CRH were extremely low. However, the same patients were tested later, it was found that their responses to CRH gradually increased and reached normal ranges approximately within one year after tumor removal, which coincided with the overall improvement in their clinical signs and symptoms due to adrenal insufficiency. In contrast, the recovery of the pituitary adrenal function in patients who had Cushing's syndrome due to an adrenal adenoma was not complete even one year after surgery. Thus the corticotropin-releasing factor test is a useful criteria to evaluate the recovery of the pituitary adrenal function in these patients after surgery, since the responses of plasma ACTH and cortisol to the administered CRH are parallel with the improvements in clinical signs and symptoms due to adrenal insufficiency in patients with Cushing's disease.

Adenoma↗
PubMed1985

The inter- and intra-subject variabilities of plasma GH response to human growth hormone-releasing hormone (1-44) NH2 in men.

The effects of intravenously given human growth hormone-releasing hormone (1-44) NH2 (hGRH-44) on growth hormone (GH) secretion were studied in normal men. A wide variability of intersubject GH response to hGRH-44 was observed. The peak plasma GH levels in response to 50, 100 and 200 micrograms hGRH-44 in 7 normal men were 9.1 +/- 3.2 ng/ml (Mean + SEM), 19.3 +/- 3.3 ng/ml and 22.4 +/- 4.0 ng/ml, respectively. Both the mean peak values for plasma GH response to 100 and 200 micrograms were significantly greater than that for 50 micrograms hGRH-44 injection (p less than 0.01), although there was no significant difference of the mean peak plasma GH values and mean concentrations at each time point, except for those at 120 min, when 100 or 200 micrograms hGRH-44 was administered. A significant difference in the mean amount of plasma GH secreted in response to hGRH-44 was observed only between 50 and 200 micrograms hGRH-44 injection (p less than 0.01). Furthermore, a dose-related plasma GH increase in response to hGRH-44 was not always observed in each subject. In contrast to the wide intersubject variability, the difference among responses of plasma GH to 100 micrograms or 200 micrograms of hGRH-44 given at multiple times separated by intervals of at least 1 week in each individual was relatively small.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Bilateral alpha-melanocyte stimulating hormonergic fiber system from zona incerta to cerebral cortex: combined retrograde axonal transport and immunohistochemical study.

We employed a highly sensitive combination method of retrograde tracing and immunohistochemistry to identify an alpha-melanocyte-stimulating hormone (alpha-MSH)-containing fiber pathway from zona incerta to cerebral cortex. Biotin-horseradish peroxidase injected into the parietal cortex of the rat labeled a number of neurons in the zona incerta bilaterally, and simultaneous staining with an alpha-MSH antiserum revealed that a part of these neurons are alpha-MSHergic.

Animals↗