In recent years many investigators have reported the role of the sympathetic nervous system and the catecholamines in the regulation of renin secretion. It has been recently reported that plasma dopamine-β-hydroxylase (DBH) excreted through the mechanism of the exocytosis with noradrenaline from the sympathetic postganglionic nervous endings is a mirror of the function of the sympathetic nervous system. In this investigation, blood pressure, urinary catecholamine excretion, plasma DBH activity and plamsa renin activity (PRA) have been determined in normal individuals during the mecholyl test and insulin-induced hypoglycaemia.
In the mecholyl test, plasma DBH activity and PRA markedly increased in five males who showed prominent responses of systolic blood pressure to mecholyl (S type) and changed slightly in eight males who showed minimal responses of systolic blood pressure to mecholyl (N type). It showed that there was a significant relationship between the maximal percent increases from their respective control values of plasma DBH activity and those of PRA following mecholyl.
In insulin-induced hypoglycaemia, plasma DBH activity, blood pressure and PRA remarkably increased following a large dose of insulin administration (0.15 u/kg). In a dose of 0.1 u/kg, there was no significant increase of plasma DBH activity and blood pressure.
PRA significantly increased but was lower than a large dose of insulin. Also, it showed that there was a significant relationship between maximal percent increases from their respective control values of plasma DBH activity and those of PRA following insulin administration.
These data indicate a close correlation between changes in plasma DBH activity and those of PRA during mecholyl and insulin-induced hypoglycaemia and lend additional support to the concept of sympathetic nervous system mechanism of renin secretion.

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Synthetic LH releasing hormone (LH-RH) is effective in increasing both serum LH and FSH in humans. Therefore, LH-RH is used to clarify the function of the hypothalamic pituitary ovarian axis in adult women. Variations in response to synthetic LHRH during different phases of the menstrual cycle are known. These variations may be due to changes in the ovarian secretion of sex streoid hormones during the menstrual cycle.
In the present study, effects of serum estradiol (Ed) on pituitary gonadotropin response to synthetic LH-RH were studied in 55 subjects without ovulation. Serum levels of LH, FSH and Ed were determined before and at 30 min after intramuscular administration of 100 μg LH-RH. LH and FSH levels in the serum were measured by the double antibody method of radioimmunoassay. Ed levels were determined by the radioimmunoassay method of T. Makino, using the antiserum against Ed-6-oxime-BSA donated by Dr. T. Makino and applied to the microcolumn of sephadex LH 20. Preliminary evidence about Ed levels during the normal menstrual cycle and in anovulatory women suggested that an Ed level under 30 pg/ml indicates the presence of a small amount of Ed. Therefore, 55 patients were divided into 2 groups; the low Ed group that showed low basal Ed levels (under 30 pg/ml) and the Ed normal group that showed normal basal Ed levels (over 30 pg/ml). Pituitary gonadotropin responses to synthetic LH-RH were studied in these two groups.
No statistical difference was shown between the two groups studied for basal LH level and FSH level. After LH-RH injection in the Ed normal group, serum LH level was significantly higher and serum FSH level was significantly lower than that in the low Ed group. Then, in order to clarify the difference in two groups, the ratio of LH to FSH (LH/FSH) before and after administration of LH-RH was examined. The ratio in the Ed normal group was significantly higher than one in the low Ed group before and after administration of LH-RH. Moreover, the percentage increase of the ratio was significantly larger in the Ed normal group than that in the low Ed group. A positive correlation (r=0.4228, p<0.01) was found between LH/FSH following administration of LH-RH and circulating the Ed level.
These results suggest that the response of pituitary gonadotropins to LH-RH is changed by serum Ed and that serum Ed causes a differential release of LH and FSH in response to LH-RH. The data seem to demonstrate that LH-RH and serum Ed show a complex interplay in releasing LH and FSH.

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The relationships between hormonal action and cyclic AMP as the second messenger of hormones have recently been discussed on many hormones. Lactation is influenced by various hormones, especially, insulin, prolactin, and hydrocortisone. Whether adenyl cyclase activity in the mammary gland of mouse epithelial cells has parallel relations with casein biosynthesis ability or not was examined using the mammary gland organ culture method.
Female, mid-pregnant (11-14 days), mice of DDY strain were used. Organ culture was done by the Chen's floating lens' paper method, using the hormone-added MEM media and non-added ones. Casein biosynthesis ability was measured by observing 32P incorporation into the casein molecules. Adenyl cyclase activity was estimated by the amount of ¹⁴C-cyclic AMP produced out of adenine-8-¹⁴C by the Kuo and Krishna's method. Radio isotope compounds were pulsed for 4 hours in the medium.
The experiments revealed that the added hormones had a remarkable effect on caein biosynthesis ability, but none on adenyl cyclase activity. No parallel fluctuation was observed between adenyl cyclase activity and casein biosynthesis ability, that is, the change of adenyl cyclase activity was found to have nothing to do with casein biosynthesis ability. Consequently, the cyclic AMP addition to the media showed no effect on casein biosynthesis ability.

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It is generally accepted that the sexual cycle in mammals is accomplished by the systematic coupling of components of the hypothalamo-hypophyseo-gonadal system. However, how these components are related to each other to develop the sexual cyclicity has not yet been clearly established. A gonadotropin releasing factor (GnRF), which has been extracted and purified from porcine hypothalamus and whose molecular structure was determined in 1971, has been synthesized in many laboratories. The synthetic GnRF, named LRF or LH-RH, has gonadotropin releasing activity for many species of mammals, including humans. The debut of the synthetic LRF has given us a pure material and a direct means of stimulating, relatively easily, the gonadotroph cells in the anterior pituitary glands. In the present study, variations in the gonadotropin releasing activity of the pituitary gland in relation to synthetic LRF was investigated throughout the sexual cycle of rats. The relationship between pituitary sensitivity and levels of steroid hormones in the blood is discussed.

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It has been confirmed in numerous studies that the hypoglycemic effect of sulfonylureas is mainly owing to its insulinogenic action. Intravenous administrations of the drugs have been adopted in many of these studies. But the oral administrations of the drugs in a few studies lead to conflicting results concerning its insulinogenic action.
In this study, the concentrations of blood glucose, serum immunoreactive insulin (IRI), serum free fatty acid (FFA) and serum tolbutamide were measured following the oral administration of single dose of tolbutamide in six normal and eleven maturity onset mild diabetic subjects. The same parameters were measured after the oral administration of tolbutamide plus sodium bicarbonate in six normal subjects. The changes of these parameters were compared with the changes following the intravenous administration of sodium tolbutamide in six normal subjects.
The oral administration of three grams of tolbutamide alone caused a gradual but significant decrease of blood glucose level. Serum FFA response showed an initial decrease, followed by a rebound elevation. In spite of 21 per cent reduction of blood glucose level, serum IRI level did not show any significant change throughout the observation for five hours. Serum tolbutamide concentration rose gradually and reached to 24.4±3.9 mg per 100 ml (Mean±SEM) at the end of the observation.
Almost identical results were obtained in diabetic subjects.
Three grams of tolbutamide plus the same dose of sodium bicarbonate were administered orally to the normal subjects. A profound decrease of blood glucose level with a nadir (35 per cent reduction) at 45 minutes and a significant increase of serum IRI level with a peak (273 per cent increase) at 20 minutes were obtained, and associated with a comparatively rapid elevation of serum tolbutamide concentration reached to 31.9±3.3 mg per 100 ml after three hours.
From these results, it is suggested that slow rise of serum tolbutamide concentration after the oral administration of tolbutamide alone might lead to moderate secretion of insulin and sooner rise might evoke larger secretion into the pancreatic vein, and that an existence of moderate hyperinsulinism in the pancreatic venous blood after the oral administration of tolbutamide alone might cause a decrease of gluconeogenesis in the liver. And the failure of serum IRI response in the peripheral venous blood in spite of hyperinsulinism in the pancreatic vein might be due to hepatic trapping of the secreted insulin.

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The mode of action of sulfonylureas as hypoglycemic agent is not clarified yet. But it has been said in general to act by increasing the secretion of insulin from the beta cells. While, some believe that their effect is independent on insulin secretion.
In the previous report, it was demonstrated that the oral administration of single dose of tolbutamide failed to increase immunoreactive insulin (IRI) in the peripheral vein in spite of significant decrease of blood glucose and free fatty acid levels both in normal and diabetic subjects.
In order to observe changes of IRI level in the pancreatic vein following the oral administration of single dose of tolbutamide, the present study was carried out to deter-mine serum IRI level of the pancreatic and peripheral vien in dogs.
Mongrel dogs of both sexes, weighing 7-12 kg were anesthetized with sodium pentobarbital. A catheter was inserted into the superior pancreatico-duodenal vein through its duodenal branch after a laparotomy. Another catheter was inserted into the femoral vein for the collection of peripheral venous blood. The experiment was started one hour after the operation.
Blood glucose level decreased gradually to 39 per cent reduction of the previous level at 180 minutes after intragastric administration of single dose of tolbutamide (0.1 g per kg). Serum IRI level in the peripheral vein showed only slight increase, similar to the response in man. While, pancreatic vein IRI level increased gradually and showed a fourfold increment after 180 minutes (from 143 μU per ml to 556 μU per ml), associated with a constant elevation of plasma tolbutamide concentration which showed 6.4 mg per 100 ml after 180 minutes.
Simultaneous administration of 0.1 g per kg of tolbutamide and the same dose of sodium bicarbonate caused 49 per cent reduction of blood glucose level and a doubling of the basal IRI level in the peripheral vein. Serum IRI level in the pancreatic vein rose sharply and demonstrated a peak at 90 minutes (620 per cent increase). The elevation of plasma tolbutamide concentration was somewhat more rapid than that after tolbutamide alone.
From these observations, it was confirmed that an apparent secretion of insulin into the pancreatic vein was induced by the oral administration of tolbutamide alone, in spite of the lack of increase in the peripheral vein IRI. And it is emphasized that the changes of insulin level in the pancreatic vein should be taken into acount in a study of insulin dynamics.

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