Several reports have revealed that human prolactin increases during pregnancy, not only in maternal and fetal serum but also in the amniotic fluid. The source and the role of prolactin in the amniotic fluid however, have not been clear up to now.
In their incubation experiment, Riddick et al (29) proved that decidual tissue at term could secret immunoreactive prolactin (IR-PRL). In order to investigate the source of PRL in the amniotic fluid, we extracted IR-PRL from decidual or villous tissue in early normal pregnancies and measured it by a double antibody radioimmunoassay in this experiment.
The results were the following :
1) We were able to measure IR-PRL from decidual or villous tissue in early pregnan-cy, the dilution curve of which paralleled pituitary standard prolactin. The cross reaction of a PRL standard preparation with HCG and HPL was not recognized within 10 μg/ml.
2) In human decidual tissue, the IR-PRL concentration began to increase at about the sixth week, arrived at the peak value, 81.06 ± 2.13 ng/0.1 g dry weight (d.w.) in the eighth week, and did not change significantly after that. In human villous tissue, although the IR-PRL concentration was distinctly lower than it was in the decidual tissue, it increased gradually and reached the level of 37.44 ± 7.16 ng/0.1g d.w. in the tenth week.
3) The extracted material (IR-PRL) from these two tissues in the 8th week, amniotic fluid at term, and pituitary standard PRL were passed through a Sephadex G-100 column (2×93 cm) with phosphate buffer and saline (0.01M, PH 7.4). In the chromatogram of these four test materials, one peak of IR-PRL was observed. The peak of IR-PRL of decidual and villous tissues and amniotic fluid revealed almost the same fraction number but elevated after the pituitary PRL preparation.
4) By gel filtration, the IR-PRL was able to be differentiated from HCG but not from HPL. The peak of HCG appeared earlier than the peak of IR-PRL and HPL.
5) The distribution of IR-PRL between human decidual and villous tissues was significantly different from that of HPL. IR-PRL concentration was higher in the decidual tissue than in the villous tissue, while HPL concentration was higher in the villous tissue than it was in the decidual tissue. From this observation, we could consider that the sources of these two hormones were different.
The results of these experiments suggest that one of the sources of PRL in the amniotic fluid was the decidual tissue.

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In order to elucidate the mechanism of hyperinsulinism following a treatment with glucocorticoid, insulin secretion induced with glucose or tolbutamide was investigated by a perifusion experiment on isolated islets of rats. The results are summarized as follows;
1. The fasting blood glucose level was significantly higher on the 2nd day (174.0 ± 11.8 mg/dl) and 3rd day (179.6 ± 9.5 mg/dl) in the glucocorticoid treated rats, than it was in the control rats (129.0 ± 12.0 mg/dl). The serum insulin levels began to increase from the first day following the glucocorticoid treatment (17.2 ± 1.3 μU/ml in the control rats, 27.6 ± 2.1 μU/ml on the 1st day, 32.4 ± 3.9 μU/ml on the 2nd day, and 34.5 ± 1.4 μU/ml on the 3rd day).
2. The insulin content of the islets decreased with the glucocorticoid treatment (765.6 ± 34.5 μU/islet in the control rat, 576.6 ± 25.0 μU/islet on the 1st day, 629.2 ± 36.9 μU/ islet on the 2nd day, and 482.0 ± 43.5 μU/islet on the 3rd day).
3. In the perifusion experiment, a biphasic pattern of insulin secretion was demonstrated with the stimulation of glucose in the control and glucocorticoid treated rats.
A remarkable enhancement of insulin secretion was observed by the stimulation of 100 mg/d1 glucose.
The amount of insulin secretion at the first phase (up to 7 min. after the glucose stimulation) was 2.9 ± 0.5 μU/islet on the 1st day, 2.7 ± 0.3 μU/islet on the 2nd day and 3.8 ± 0.1 μU/islet on the 3rd day; these amounts were high compared with that of 1.8 ± 0.1 μU/islet in the control rat. The amount of insulin secretion at the second phase (8 to 60 min. after the glucose stimulation) was 28.5 ± 2.5 μU/islet on the 1st day, 37.1 ± 3.3 μU/islet on the 2nd day and 41.3 ± 1.8 μU/islet on the 3rd day; these amounts were higher when compared with that of 24.7 ± 0.7 μU/islet in the control rat.
4. The monophasic insulin secretion from isolated islets by the stimulation of tolbutamide was enhanced with the treatment of glucocorticoid.
These results indicate that glucocorticoid directly enhances insulin secretion from the pancreatic islets at the physiological concentration of blood glucose, which seems to be an important factor in the occurrence of hyperinsulinemia associated with glucocorticoid therapy.

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The properties of specific binding of ³H-naloxone, opiate antagonist, were studied in a particulate fraction from a rat brain. The specific binding was time and pH dependent, saturable with respect to ³ H-naloxone and tissue concentration. The binding of ³ H-naloxone could be described on the basis of two independent binding sites with apparent Kd of 3 nM and 57 nM, respectively. Receptor binding of ³H-naloxone was enhanced by Na⁺ and Li⁺ but not by K⁺, and the divalent cations depressed the specific binding. When 100 mM sodium was included in the incubation medium, the number of apparent high affinity binding sites was almost doubled, but the number of low affinity sites was unaffected, and there was no significant effect on the dissociation constants. Non radioactive opiates and synthetic endorphins were incubated with ³H-naloxone and rat-brain homogenate in the absence and presence of 100 mM NaCl, and the concentration of the drug required to give 50% inhibition of binding (IC₅₀) was determined by a log-probit analysis. When the bound radioactivity was separated by filtration through a glass-fiber filter, the sodium index (IC₅₀ + NaCl/IC₅₀-NaCl) for naloxone was 1, while levallorphan and pentazocine, mixed agonist-antagonists, exhibited the sodium index of 2.2 and 3.3, respectively. The sodium index for agonists, morphine and synthetic endorphins, ranged between 50-307. When the centrifugation method was used to isolate the ³ H-naloxone-receptor complex, the sodium index for mixed agonist-antagonists and agonists were 2-fold and 4-10-fold, respectively, while the sodium index for the antagonist was unaffected.
Opioid receptor distribution, determined by the specific binding of ³H-naloxone, was examined in the 8 regions of a rat brain. Opioid receptors were highly localized in the corpus striatum, thalamus plus subthalamus and hypothalamus, and negligible in the cerebellum. Brain enkephalin activity, determined by an opioid radioreceptor assay with methionine-enkephalin as standard, had a similar regional distribution to that of the opioid receptors, with the highest level in the corpus striatum and the lowest level in the cerebellum. However, there were some discrepancies between regional variations for enkephalin activity and the opioid receptor, which may be ascribed to variable composition and characteristics of endogenous opioid substances in various brain regions.

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For the purpose of studying the metabolism of adrenocortical steroids in primary aldosteronism, diurnal variation and the effect of dexamethasone were examined in four patients.
The circadian rhythm of cortisol was observed in plasma aldosterone and corticosterone in all cases in the preoperative state. With regards to plasma progesterone, 17α-hydroxyprogesterone and dehydroepiandrosterone-sulfate, however, no demonstrable change was noted.
Dexamethasone was administered to two subjects for 10 days before the operation. As a result, the urinary aldosterone of one subject decreased on the 5th day after the administration but was restored to its original value on the 10th day, while the urinary aldosterone of the other subject did not decrease at all.
On the first day after the operation, the value of plasma cortisol was elevated, losing its circadian rhythm. On the 7th day after the operation, the normal circadian rhythm. On the 7th day after the operation, the normal circadian rhythm was observed again in plasma cortisol. Plasma aldosterone was reduced to the normal range without any demonstrable changes on the first and 7th days after the operation. On the 30th day after the operation, a slight cortisol-like circadian rhythm was observed.
Plasma levels of progesterone, corticosterone, 17α-hydroxyprogesterone and dehydroepiandrosterone-sulfate were almost within the normal range throughout the pre-and post-operative periods. Although plasma progesterone was within the normal range, it tended to be lower in the postoperative state than in the preoperative state.

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To study the secretion of adrenocortical steroids, the renin releasing test and the angiotensin II analog (1-Sar, 8-Ala-Angiotensin II) infusion test was performed on four subjects with primary aldosteronism.
The plasma renin activities of these subjects in the preoperative state were rather low, without any response to the renin releasing test. Plasma aldosterone was, however, significantly high and showed a tendency to declineits value when the subject was in an upright position.
In the preoperative state, all the subjects lacked any alterations in plasma renin activity throughout the angiotensin II analog infusion test. Though slight elevations were observed in the blood pressure of three subjects, there was no demonstrable change in plasma aldosterone. In the other subject, though blood pressure did not change, plasma aldosterone exhibited a remarkable rise as did progesterone, 11-deoxycorticosterone and corticosterone. From these data, it was suggested that in the latter subject the aldosterone secretion was sensitive to angiotensin in comparison with ACTH.
Three weeks after the operation, it was observed that plasma aldosterone response decreased, while the response of plasma renin activity to the renin releasing test was normal. This is considered to be due to the diminished sensitivity of the glomerulosa of the non-adenomatous adrenal gland to angiotensin.
The levels of 17a-hydroxyprogesterone, 11-deoxycorticosterone and corticosterone were almost within the normal range in the pre-and postoperative state. The levels of plasma progesterone and 11-deoxycorticosterone, however, tended to be lower in the postoperative state compared with the preoperative state.

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Patients with diabetes mellitus have a higher incidence of arteriosclerotic cardiovascular diseases than does the nondiabetic population of similar age. The factors that dispose a diabetic patient to early arteriosclerosis are not well understood. It has been indicated that premature arteriosclerotic cardiovascular diseases are accelerated in the presence of elevated level of plasma low density lipoprotein (LDL) or reduction of plasma high density lipoprotein (HDL) concentration. Recently, there has been an upsurge of interest in the role of HDL in determining the risk of ischaemic heart disease. The purpose of the present study was to investigate the effects of various types of treatment such as diet, glibenclamide and insulin on plasma lipids and lipoprotein concentration in diabetics and the relationship between plasma lipoprotein fractions and diabetic control. Treatment of diabetes mellitus was reevaluated from the standpoint of HDL metabolism. One hundred and three diabetic patients (50 men and 53 women) who has been admitted in the hospital and on standard diet for diabetes mellitus, have been studied. The diagnosis of diabetes mellitus was established by 50 g oral glucose tolerance test and other clinical signs and symptoms. Following patients were ruled out of the present study : 1) the patients who had liver dysfunction, endocrinological disorders such as thyroid disease and renal complications suggested by proteinuria and elevated serum creatinine level etc., 2) the patients who were treated by drugs which possibly affect lipoprotein metabolism, 3) the patients who were obese more than 10% of ideal body weight. Plasma lipoproteins were fractionated by sequential ultracentrifugation at densities 1.006 and 1.063 g/ml in a type 40.3 rotor on the Beckman L5-50 ultracentrifuge and very low density lipoprotein (VLDL : d<1.006 g/ml), low density lipoprotein (LDL : 1.006<d<1.063 g/ml) and high density lipoprotein (HDL : d>1.063 g/ml) were obtained. Cholesterol (Ch), triglyceride (TG), phospholipid (PL) and apolipoprotein B in original plasma, VLDL, LDL and HDL fractions were determined. Cholesterol in plasma, VLDL, LDL and HDL did not show significant differences among adult onset diabetics, juvenile onset diabetics and controls. A diagnosis of juvenile onset diabetes was made, if diabetes had its onset before age 25. HDL-Ch/LDL-Ch ratio was the highest (0.45 ±0.18) in insulin treated diabetics and the lowest (0.35 ±0.06) in adult onset diabetics treated with glibenclamide. These were no significant differences in TG and PL in plasma and each lipoprotein density class between diabetics and controls, except a significant increment of VLDL-TG in juvenile diabetics and a significant decrease of VLDL-PL in insulin treated diabetics, as compared to respective controls. The heterogeneity of the diabetic populations studied as well as differences in the state of diabetic control, age, sex, body weight, smoking, diet, alcohol consumption etc. have led to much confusion and controversy as to the lipoprotein, especially HDL, concentration in diabetics. Therefore, changes of lipoprotein in diabetic patients were followed up before and after treatment with diet, glibenclamide or insulin to eliminate the effects of these factors. VLDL and LDL were decreased and HDL was increased with insulin treatment. However, glibenclamide induced a significant decrease in HDL-Ch. Since a reduction in plasma HDL may accelerate the development of atherosclerosis and ischaemic heart disease, these results may help to explain the University Group Diabetes Program's findings which showed a higher incidence of mortality of coronary heart disease in diabetics treated with sulfonylurea. Relationship between TG-rich lipoproteins and HDL metabolism was studied. A significant negative correlation was found between pretreatment VLDL-TG and changes of VLDL-TG with insulin therapy,

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To elucidate the mechanism of blood pressure control in essential hypertension (EH), plasma norepinephrine concentrations (PNE), plasma renin activity (PRA), cardiac index (CI) and total peripheral resistance (TPR) were determined in normal subjects and those suffering from EH while resting and after standing with furosemide.
The results were as follows :
1) PNE were 204 ± 100 pg/ml (mean ± S.D.) in normal subjects and 313 ± 257 pg/ml in EH. PNE in EH were not significantly greater than in normal subjects, but in some patients with EH, PNE were above normal.
2) In both normal subjects and those suffering from EH, PNE and PRA showed a positive correlation (r = 0.45, p<0.05; r = 0.52, p<0.001; respectively).
3) In low renin EH, the response of PNE to the stimulation of standing with furosemide was significantly greater than in normal renin EH (p<0.05).
4) PNE in EH were independent of both TPR and CI.
5) There was a positive relation between PRA and CI (r = 0.44, p<0.05), and a slight negative relation between PRA and TPR (r = -0.36, 0.05<p<0.1).
These results suggest that sympathetic nervous hypertonicity may be responsible for the activation of the renin-angiotensin system and that the interaction of both the sympathetic nervous system and the renin-angiotensin system may play an important role in the elevation of blood pressure. In low renin EH, the response of PNE to the stimulation of standing with furosemide may be normal and blood pressure may be controlled by both the sympathetic nervous system and the renin-angiotensin system.

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The role of circulating somatostatin in triglyceride (TG) homeostasis, especially in TG entry from the gastrointestinal tract, was evaluated on the lymph of the canine thoracic duct in fasting and postprandial states.
Cyclic somatostatin at a near physiologic (50 ng/min) and a pharmacologic (5μg/min) dosis was infused through either the portal or the femoral vein, and the lymph were collected at every 10 min through a cannula inserted into the thoracic duct under neuroleptanalgesia.
The results were as follows :
1) The levels of the lymph flow rates in the fasting state were significantly reduced to a mean of 87.0 ± 2.7, 91.0 ± 0.9% of the preinfusion values during somatostatin infusions at the rate of 50 ng/min through the portal and femoral veins, respectively, and to a mean of 78.0 ± 2.3, 80.3 ± 1.9% at the rate of 5 μg/min, respectively. The somatostatin infusions at these rates through either the portal or the femoral vein induced almost identical attenuating effects on the lymph flow rate whereas no significant changes in the flow were observed during saline infusion.
2) The effects of the somatostatin infusions on the lymph of fasting subjects at both rates through either the portal or the femoral vein were abolished by the vagotomy at the level of the diaphragm performed 1 hr prior to the infusions.
3) The levels of the flow rate, TG concentration, and TG content (flow×TG concentration) of the lymph which were obtained 3 hrs after the ingestion of a fat-protein rich meal were reduced to a mean of 80.9 ± 4.1, 80.0 ± 4.2, and 66.1 ± 5.3% of the basal values during the intraportal somatostatin infusion at the rate of 50ng/min, respectively, and to a mean of 91.1 ± 0.9, 84.4 ± 8.8, and 79.1 ± 8.0% during the intrafemoral infusion, respectively. These values were significant except changes of TG concentration. Whereas, somatostatin infusion at the rate of 5 μg/min into the portal vein induced significant reductions of the flow, TG concentration and TG content to a mean of 81.0 ± 10.1, 77.9 ± 5.9, and 62.3 ± 3.5%, respectively, and into the femoral vein to a mean of 84.7 ± 4.0, 66.1 ± 7.7, and 56.2 ± 7.3%, respectively. On the postprandial lymph, somatostatin infusions at these rates through either the portal or the femoral vein also induced almost identical levels of the attenuating effects on those parameters.
4) The pressures in the portal vein and the abdominal aorta and heart rate showed no changes during somatostatin infusions both at the rate of 50 ng/min and 5 μg/min through either the portal or the femoral vein in the fasting state of normal and vagotomized dogs.
These results indicate that somatostatin could retain almost the same potency on the thoracic duct lymph even though it passes through the liver both at a near physiologic and at a pharmacologic dose in the face of the vagus nerve and suggest the possibility that circulating somatostatin from the pancreas or other splanchnic organs might have a physiologic influence upon TG entry from the gut through altering dynamics of the splanchnic lymph system.

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