The effects of various amine compounds on the conversion of ProPTH to PTH in bovine parathyroid slices were studied.
Bovine parathyroid slices were incubated in Earle's balanced salt solution with or with-out the designated amine compound (pH 7.4) at 37°C for up to 120 minutes. ³H-leucine was added to the incubation medium 30 to 60 minutes before termination of incubation. The incubated tissue slices and medium were homogenized together in 8M urea, 0.2N HCl and 0.01M cysteine solution by Polytron homogenizer. A crude hormonal extract as TCA-powder was prepared through fractionation with organic solvent and salt followed by precipitation of the hormonal peptides with 7.5% TCA. The TCA-powder was further fractionated through CM-cellulose chromatography in order to separate radioactive ProPTH from PTH.
Primary, secondary and tertiary amines as well as inorganic ammonium compounds, especially ammonium chloride (pH 7.4), inhibited the conversion of ProPTH to PTH, while quarternary amine, diamine and polyamine did not. Monoamine-induced inhibition of the conversion of ProPTH to PTH was time- and dose-dependent. Such inhibition by amines of the conversion of ProPTH to PTH was reversible in diethylamine and irreversible in tris (OH) methyl-aminomethane.

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Basic and clinical studies on TRH activity of L-pyro-glutamyl-L-histidyl-L-prolineamide-L-tartrate-monohydrate (TRH-T) were performed.
The biological activity and immunological activity of TRH-T were almost the same as those of TRH.
500 μg of TRH-T was administered intravenously to 12 normal subjects and 55 patients with endocrinopathy. The blood samples were taken after TRH-T injection for measurements of serum TSH, PRL, triiodothyronine (T₃), thyroxine (T₄), LH, FSH, GH and cortisol levels by radioimmunoassay. In 12 normal subjects, peak levels of serum TSH after TRH-T injection were distributed from 6.3 μU/ml to 27.1 μU/ml. Serum PRL, T3 and LH levels were increased, but serum cortisol levels were decreased significantly after TRH-T injection. Serum T₄, FSH and GH levels were not changed significantly after TRH-T injection.
In 55 patients with endocrinopathy, the responsiveness to TRH-T injection was almost the same as to TRH. Serum TSH levels after TRH-T injection were hyperresponsive in primary hypothyroidism and hypothyroid state on medication, normoresponsive in nontoxic goiter, euthyroid state on medication, hypothalamo-pituitary disorders (no thyroid disorder) and tertiary hypothyroidism and hyporesponsive in hyperthyroidism and secondary hypothyroidism. Serum PRL levels after TRH-T injection were hyperresponsive in primary hypothyroidism, euthyroid state on medication and hypothyroid state on medication, normoresponsive in nontoxic goiter and hypothalamo-pituitary disorders (no thyroid discorder) and hyporesponsive in hyperthyroidism, secondary hypothyroidism and tertiary hypothyroidism.
Ten milligrams of TRH-T were administrated orally b.i.d. for 4 days to 5 normal subjects and 12 patients with endocrinopathy. Thyroidal ¹³¹I-uptake (24 hrs.) was increased after TRH-T administration in normal subjects, tertiary hypothyroidism and patients with acromegaly, but not increased in primary hypothyroidism and hyperthyroidism.
These results suggested that TRH-T has almost the same activity as TRH, and TRH-T is one of useful drug for evaluation of the pituitary function clinically.

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Intracellular T₃ concentration in leucocyte was measured by radioimmunoassay following the extraction with the method of Flock et al, (direct method) and compared to the value calculated from the leucocyte/plasma ₁₂₅I-T₃ ratio and plasma T₃ concentration (indirect method). T₃ in the leucocyte measured by direct method was 680 ng/100g with wider variation and that by indirect method was 275 ng/100g or 0.22 ng/mgDNA with smaller scatter. Considering the technical difficulty inherent to the direct method, the value obtained with indirect method would more closely reflect the intracellular concentration of T₃ in leucocytes. The ratio of T₃ in leucocyte to plasma was not significantly altered in the patients with overt hyperthyroidism.

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This study was performed in order to investigate the suppressive effect of somatostatin on the endocrine pancreas in Ketalar-anesthetized dogs.
In the 1st group, somatostatin was administered (250μg in one shot followed by infusion for 30 minutes at the rate of 0.8μg/kg/min), the blood sugar level declined about 20mg/dl at 20 minutes. Plasma insulin (IRI) decreased to 10±3μU/ml at 3 minutes from 15±3μU/ml, but it was not significant, and plasma glucagon (IRG) to 23±5pg/ml at 3 minutes from 72±6pg/ml. Both values recovered to the basal value at 10 minutes after the termination of infusion.
In the 2nd group, tolbutamide (i.v. 1.0g) was administered with somatostatin in the same manner as described above, the blood sugar level declined about 10mg/dl at 1 minute, while IRI decreased a little, but it was not significant. On the other hand, in the control, the blood sugar level declined markedly with a rise of IRI following tolbutamide administration. IRG changed a little after tolbutamide administration alone, but together with somatostatin IRG decreased to 23±7pg/ml at 15 minutes from 80±6pg/ml.
In the 3rd group, both glucose and somatostatin were infused at the rate of 130mg/kg/ min and 1.6μg/kg/min, respectively, for 15 minutes after the initial bolus administration of somatostatin. The blood sugar level increased markedly to 1460±86mg/dl at 15 minutes, but IRI decreased a little, while IRI increased markedly in the control with glucose alone.
In the 4th group, hydrocortisone was administered with glucose and somatostatin. No increase of IRI was observed.
In the 5th group, arginine was administered at the rate of 130mg/kg/min together with somatostatin (1.6μg/kg/min), the blood sugar level declined about 30mg/dl at 15 minutes, while IRI decreased a little and IRG decreased to 28±5pg/ml from 82±13pg/ml. On the other hand, in the control with arginine alone, both IRI and IRG increased markedly.
These results demonstrate that somatostatin suppresses the endocrine pancreatic function when the stimulator was administered as well as in the fasting state.

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In this paper, the author reported on the clinical evaluations of plasma renin activity (PRA) and plasma aldosterone concentration (PAC) by simultaneous measurement using radioimmunoassay techniques of the same plasma samples withdrawn from the patients with various endocrine and hypertensive diseases and from the patients with idiopathic edema.
1) In normal subjects (i.e. 6 healthy male adults), the values obtained were as follows : PRA was 3.95±2.03 (Mean±SEM) ng/ml/hour and PAC was 5.81±3.60 (M±SEM) ng/100ml in recumbent and supine positions. After furosemide-loading tests (i.e. standing upright and/ or walking for 2 hours after administration of furosemide 40 mg intravenously), PRA and PAC rose to 13.70±2.80 ng/ml/hour, and 17.05±5.48 ng/100 ml, respectively.
2) Of the 13 patients with essential hypertension, in most of the low renin group (4 cases) low values of PAC were obtained, and in normal renin group (9 cases) normal or exaggerated responses were observed after salt restriction and/or furosemide-loading test.
3) In the patients with primary aldosteronism (i.e. 9, preoperative, and 7, postoperative), the simultaneous measurement of PRA and PAC was useful for preoperative clinical diagnosis, for determination of localization of adrenocortical adenoma, for the differential diagnosis from low renin essential hypertension, and for the postoperative and pathophysiologic understanding in the fields of renin-angiotensin-aldosterone axis.
4) In the 4 patients with Cushing's syndrome, a case of adrenal carcinoma disclosed a dissociation of PRA and PAC values (extremely high PRA and low PAC), and the other 3 cases of adrenal hyperplasia showed normal values of PRA and PAC.
5) Though 4 patients with Addison's disease showed high PRA and extremely low PAC, 4 patients with hypopituitarism including 3 cases of Sheehan's syndrome showed normal PRA and low or lower limits of normal PAC, and additional 2 cases of this disorder associated with cerebral hypernatremia showed extremely high PRA levels.
6) In 5 patients with acromegaly, 2 cases of the hypertensive group showed suppressed responses of PRA and PAC after furosemide-loading tests, and 3 cases of the normotensive group showed normal responses after the same loading tests.
7) In 8 patients with anorexia nervosa, 3 cases showed low PRAs, 2 cases showed high PRAs, and several of them disclosed a dissociation of PRA and PAC, but the pathogenesis or implication was not clarified.
8) A case of pheochromocytoma associated with neurofibromatosis showed high PRA and PAC levels, and exaggerated responses for furosemide loading, preoperatively; but both parameters recovered to normal, postoperatively.
In each case of hyperthyroidism and idiopathic edema, high PRA and normal PAC were observed.
9) In a case of Prader-Labhart-Willi's syndrome with glomerulosclerosis and of Kimmelstiel-Wilson's syndrome, PRA and PAC values were within normal range.
10) In a case of Bartter's syndrome manifesting secondary aldosteronism, and of extrarenal ectopic renin-secreting orbital and brain tumor manifesting primary reninism, both patients disclosed specific pathophysiologic states of dominant high PRAs rather than hyperaldosteronism.
11) Inconclusion, the simultaneous measurement and clinical evaluation of PRA and PAC were significantly evaluated in : (1) a test for stimulation of renin release, (2) a screening test for secondary or symptomatic hypertension, (3) the differential diagnosis between low renin essential hypertension and primary aldosteronism, (4) the determination of localization of adrenal tumor by selective adrenal vein sampling in primary aldosteronism, and (5) the understanding of pathophysiology in secondary aldosteronism.

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Effects of mestranol, one of the synthetic estrogens, on the pituitary responses to a synthetic LH-RH were investigated.
Seven normal women with regular menstrual cycles were used as controls in the late proliferative phase. Thirteen healthy volunteers with normal ovulating cycles were devided into 2 groups. Five women received orally 20μg per day (Group I) and other 8 women were administered 40μg per day (Group II) of mestranol, beginning from the 5th day of the cycle for a period of 10 days. Volunteers in each group were kept fasting overnight and 5ml of blood was drawn at 9 to 10 am on the day of the experiment. Ten minutes after drawing blood, 200μg of synthetic LH-RH was injected subcutaneously in the late proliferative phase in the normal women with regular menstrual cycles. According to the same procedure, women taking mestranol were administered LH-RH on the 8th to 10th day after the beginning of taking the first administration. Three ml of blood was taken at 15, 30, 60,120 minutes and 24 hours after injection of synthetic LH-RH. Serum levels of LH and FSH were determined by the double antibody radioimmunoassay. The 2nd IRP-HMG was used as the standard materials and expressed as mIU/ml of serum.
Mean baseline serum LH and FSH concentrations were not significantly changed by doses of mestranol used in this experiment. In Group I and Group II, mean LH levels were not significantly altered within 60 minutes after the subcutaneous administration of LH-RH. Thereafter, mean LH levels continued to rise and reached a peak at 120 minutes after injection of LH-RH in contrast with the control. A significant delay in the LH peak was observed in treatments with 20μg and 40μg of mestranol. In Group II, mean LH level at 120 minutes after LH-RH was significantly elevated as compared with those seen in the late proliferative phase of the cycle and in the Group I. Concerning the FSH response to LH-RH, 20μg mestranol did not induce a significant rise. On the other hand, mean FSH level in Group II at 120 minutes after injection of LH-RH was significantly elevated as compared with that seen in the late prolijerative phase. As expected, mean net increases of LH and FSH above each baseline level at 120 minutes after LH-RH in Group II were significantly greater than those of the control, but at all other points in both treated groups the mean net increases following LH-RH were not markedly changed. Moreover, the maximum LH increase in the treatment of 2 doses of mestranol occurred later than that seen in the control. However, in terms of percent changes from baseline levels LH and FSH releases to LH-RH at 120 minutes were not significant.
From these results, it was suggested that mestranol at a dose of 40μg exerted a direct action on the pituitary gonadotropin response to LH-RH. The prolonged response of LH following administration of LH-RH in the mestranol-treated women was seemed to be related to the increased sensitivity of the pituitary. The time-course of changes in serum LH and FSH with LH-RH may reflect a dual role of LH-RH in regulating releases and repletions of pituitary gonadotropins in the treatment of 40μg mestranol. The initial responses of LH and FSH within 60 minutes after injection of LH-RH revealed appearently the release of readily releasable components. On the other hand, the repletion at 120 minutes was presumably stimulated in addition and in consequence newly synthesized LH and FSH, subsequently released. Thus, mestranol enhanced the sensitivity of pituitary gonadotrophs to LH-RH in normal women with regular menstrual cycles. Moreover, the nature of the modulating effect of estrogen on pituitary responsiveness to LH-RH was dependent on the dosage and the duration of the exposure.

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