The effect of beta adrenergic blocking agents on the renin release from the kidney and its possible role in the hypotensive effect of these agents were studied in patients with essential hypertension.
Oxprenolol induced a significant decrease in systolic blood pressure and PRA, but the correlation between the decrease in blood pressure and the decrease in PRA was not found. When the effect of carte olol, another beta adrenergic blocking agent, was studied, a decrease in blood pressure was obtained, but there was a rise in PRA.
These observations suggest that the hypotensive action of beta adrenergic blocking agents does not result from their effects on PRA.

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In order to clarify the physiological role of somatostatin in insulin release, isolated rat pancreatic islets were treated with anti-somatostatin serum and challenged by glucose and leucine. The pancreatic islets were isolated from male Wistar rats with collagenase by the method of Lacy and Kostianovsky and subject to the following two models of experiments.
1] Ten islets were pre-incubated in 500 μl of Krebs-Henseleit bicarbonate buffer, pH 7.4, (KHBB) containing 3.3 mM glucose and 0.5% bovine serum albumin (BSA) for 20 minutes under a gas phase of 95% O₂-5% CO₂ at 37°C. They were subsequently transferred to a medium (KHBB) containing various concentrations of somatostatin ranging from O to 10 μg/ml, and incubated for 10 minutes in 3.3 mM and 16.7 mM glucose, under the same conditions as in the first incubation.
Insulin released in the medium at the last incubation was measured by radioimmunoassay using rat insulin as a standard. The results were expressed not only as actual measurements but also as percents of values of insulin release in the control group. Inhibition by somatostatin of 16.7 mM glucose-induced insulin release was observed at its concentration of 1 μg/ml and 10 μg/ml; the value was 59.5 ± 5.9% (n=6) and 37.9 ± 5.3% (n=6) of the control value at the former and the latter concentration of somatostatin, respectively. But no inhibitory effect by somatostatin was observed at 3.3 mM glucose.
2] Antiserum to somatostatin (cyclized form) was produced in rabbits according to the description of Arimura.
Five islets were incubated in 400 pl of KHBB and 100 μl of anti-somatostatin serum containing 0.5% BSA and 3.3 mM glucose for 60 minutes at 37°C under a gas phase of 95% O₂-5% COO₂. After the incubation they were rinsed three times in KHBB supplemented by 3.3 mM, 8.3 mM or 16.7 mM glucose in addition to 0.5% BSA, followed by another 60 minutes incubation under the same conditions as in the first incubation.
For the control studies, anti-somatostatin serum was replaced by normal rabbit serum, otherwise the procedure was identical with the experimental studies. Insulin released from the islets treated by anti-somatostatin serum was 414.1±54.0% (n=5) and 129.4 ± 4.8% (n=5) at 3.3 rnM and 8.3 mM glucose, respectively; both were significantly elevated compared with the control. However, 132.7 ± 7.0% (n=3) at 16.7 mM glucose was not significantly different from the control, although it was enhanced to a certain degree. Similarly insulin release induced by 10 mM 1-leucine and 10 mM 1-leucine plus 3.3 mM glucose was enhanced by prior treatment by anti-somatostatin serum, i.e; 606.1 ± 73.8% (n=7) and 439.4 ± 38.4% (n=7) respectively, as compared with control values, which were statistically significant.
These observations, besides the generally recognized findings of inhibition of insulin release by somatostatin, suggest that endogenous somatostatin plays a physiological role in the regulatory mechanism of insulin secretion.

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The management of thyrotoxicosis among women who are expected to become pregnant has its own special problems. Since thyrotoxic patients are often troubled with thyroid dysfunction for a long period of time, they sometimes risk a poor outcome of pregnancy. The purpose of this study is to consider the best way of treating thyrotoxic patients of childbearing age.
A retrospective study of 506 pregnancies is presented here. These 506 pregnancies are divided into three groups : first, the 170 patients who became pregnant during antithyroid drug therapy, (D.D.); second, the 125 patients who became pregnant after completing antithyroid drug therapy, (A.D.); and third, the 211 patients who became pregnant after subtotalthyroidectomy, (A.S.).
In D.D. and A.D., patients sometimes became pregnant when they were hyperthyroid. In these cases, the fetal losses were more than 20%. On the other hand, when the patients became pregnant in euthyroid, the fetal losses of each group were 14.1% and 7.4%, respectively. In D.D., 22% of the patients became hyperthyroid during pregnancy, while 10% did in A.D.. There were some cases which became hypothyroid during pregnancy : these were 10% in D.D. and 1.6% in A.D.. 70% in D.D. and 60% in A.D. were relapsed after delivery.
As for the A.S. group, the fetal loss among cases with normal function during pregnancy was 7.8%. In seven pregnancies in A.S., supplemental hormone therapy had started before pregnancy because of hypothyroidism and there was only one fetal loss. Three of the 10 in A.S. who were hypothyroid during pregnancy without receiving thyroid hormone failed to carry their infants alive. In A, S., there were 127 cases in which thyroid function was not examined during pregnancy and fetal loss among them was as high as 26.8% (34 cases), Sixteen of them were found to have overt hypothyroidism or subclinical hypothyroidism judging from a rise in serum TSH after delivery, and were suspected of being hypothyroid during pregnancy.
Of the 422 neonates in this series, 7 had anomalies (1.7%). There was no goitrous neonate. Of the 161 infants whose mothers had taken methimazole in their first trimester, three had anomalies (1.8%) including umbilical hernia and Fallot's tetrad. In these cases, the mothers had received more than 15 mg of methimazole per day.
These results may suggest that if patients become pregnant during drug therapy, their thyroid functions will become unstable during pregnancy more often and they will have a higher percentage of relapses after delivery as compared with those who become pregnant after drug therapy. In addition, it has not been denied that maternal antithyroid drug therapy might have a bad effect on the fetus. Therefore, patients should be recommended to become pregnant after completing drug therapy and should be careful not to become pregnant when they relapse.
As for surgery, relapses occurred infrequently indicating that there is less effect of hyperthyroidism on pregnancy; in addition, there is no need to worry about drug influence on the fetus and relapse after delivery. Since, it takes much time to complete drug therapy, subtotalthyroidectomy may be thus considered to be the best kind of therapy, especially for the patients who are planning to become pregnant in the near future. But in these cases a thyroid function test should sometimes be done after the operation so as not to risk patients being in a hypothyroid state. Appropriate replacement therapy with thyroid hormone should be given, if necessary.

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The effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen on ovarian follicle growth was studied in hypophysectomized rats using the histologic technique.
After the administration of FSH to hypophysectomized immature female rats, many growing follicles of different sizes were observed. In particular, there was an increase in the number of large growing follicles with a thickening of the theca layer. Moreover, the administration of FSH caused many follicles to induce antrum or cavity formation. Although the administration of LH resulted in the repair of interstitial cells, there was no resulting follicle growth. On the other hand, the administration of estrogen caused small follicles to develop into medium-sized follicles with multi layers of granulosa cells, containing a large number of mitoses but no antrum.
In effect, the administration of both FSH and estrogen caused some follicles to grow, but it seemed possible that the follicle growth after the administration of FSH differed in character from that after the administration of estrogen. Thus, it might be concluded that FSH stimulates the maturation rather than the growth of the follicle.

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The mode of action of the follicle-stimulating hormone (FSH) on ovarian follicle growth was studied in hypophysectomized rats using the histologic, autoradiographic and histochemical techniques.
The follicle growth was stimulated by the administration of both FSH and estrogen. The histologic finding of the follicle growth induced by the two hormones was different. Namely, after the administration of FSH, the theca layer was thick, but after the, administration of estrogen, it was thin.
³H-thyrnidine and ³H-leucine were used to investigate cell division in a growing follicle. The uptake of 3 H-thymidine and 3 H-leucine by the theca layer was enhanced remarkably by FSH. On the other hand, the uptake of ³H-thymidine by the granulosa layer was enhanced by FSH or estrogen, while the grain count of granulosa cells was increased only by the administration of estrogen.
Moreover, the administration of FSH resulted in an increase of the enzyme activity of glucose-6-phosphate dehydrogenase (G-6-PD), Δ⁵-3β-hydroxysteroid dehydrogenase (3β-HSD) and alkaline phosphatase (ALPase) in the theca layer. Furthermore, the administration of FSH caused an increase in the serum estradiol and estriol of rats, whereas the administration of estrogen did not.
It seems possible, therefore, that FSH stimulated proliferation of theca cells and produced estrogen. The results suggest that the estrogen produced by the theca cells might stimulate proliferation of granulosa cells; consequently, follicle growth might be induced.

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Estrogen priming is necessary for progesterone action, and it was demonstrated that the priming increases progesterone-receptor in the cytoplasm of the rabbit uterus. However, it is not yet known whether estrogen priming results in some changes of the nuclear constituent for progesterone action or not, while progesterone-receptor complex enters into the nucleus and binds to the chromatin acceptor site. The estrogen priming effect on the nucleus for the mechanism of action of progesterone is the subject of this paper.
The 274,200 x g supernatant of rabbit uterine homogenate was used as cytosol. The nuclei and chromatins were prepared by the method in Table 1. The cytosol labeled with 3H-progesterone was incubated with nuclei obtained from estrogen primed or castrated rabbit and then nuclear radioactivity was counted. Estrogen priming increased the nonspecific binding sites of progesterone-cytosol complex but did not increase the specific binding sites in the nuclei as in Fig. 2.
Uterine cytosol of castrated rabbit gives progesterone-5S binding and that of estrogen primed rabbit gives progesterone-8S and 5S bindings as in Fig. 1. ³H-progesterone-8S was fractionated as in Fig.1, and it was then incubated with the uterine chromatins obtained from the castrated or primed rabbits. Radioactivities of these chromatins were counted. Progesterone-8S complexes bound to both estrogen primed and estrogen non-primed chromatins in almost equal amount per DNA as in Fig. 3. It is indicated that the chromatin acceptor sites (per DNA) for progesterone-receptor complex is equal in spite of estrogen priming. The activity of RNA synthesis by progesterone-8S on the uterine chromatins of primed and non-primed rabbits was almost same in amount per DNA as in Fig. 4.
These results indicate that the function of estrogen priming on the mechanism of action of progesterone is the synthesis of progesterone-receptor and the increase of nonspecific binding sites of progesterone·macromolecule (non-specific binding protein) in the nucleus.

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The preventive effect of ursodesoxycholic acid on pancreatic injury by alloxan (alloxan diabetes) has been reported by Watari, et al. (1976).
In the following experiment, to pursue the findings further, ursodesoxycholic acid was used curatively for alloxan diabetes. A first group of animals (5 mice) were injected with alloxan (4 mg) twice at the fifth and tenth day. The second group (5 mice) was injected with ursodesoxycholic acid (0.2 mg each) for 14 days during the experiment in addition to the same alloxan dosage/frequency as the first group. A third group of animals (5 mice) served as the control.
The animals were sacrificed on the 15th day and the blood sugar levels were examined, using commercial test paper. The pancreatic tissues were fixed in a mixture of 2.5% glutaraldehyde and 2% osmic acid solution, which was adjusted at pH 7.4 with a veronal acetate buffer; the osmotic pressure was also regulated by adding sucrose of 0.045 g/ml. Following dehydration using a series of alcohol concentrations, the tissues were embedded in Epon 812. Thin sections were cut with a Porter-Blum MT-2B ultramicrotome, stained with both uranyl acetate and a lead mixture, and then observed by electron microscopy.
The results were as follows : The pancreatic islet cells, especially of B-cells in the first group of animals injected with alloxan only, were seriously damaged and contained myelinated mitochondria, Golgi apparatus, and an increasing number of autophagic vacuoles. Some B-cells revealed hydropic degeneration. Some B-granules changed into vacuoles after diacrine secretion. Pancreatic A-cells were increased in number and showed no cell injuries. On the other hand, the pancreatic B-cells of mice treated with both alloxan and ursodesoxycholic acid maintained almost normal fine structures.
In summary, ursodesoxycholic acid has a curative effect on alloxan-induced pancreatic B-cell injury.

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A mathematical model was developed for the quantitative analysis of the results of TRH stimulation tests. The derived equation indicating plasma TSH concentration (C) at arbitrary time (t) after TRH was as follows :
C₀=α/β-α·Q₀ /V (e^-αt-e^-βt) +C₀e^-βt
where
α = rate constant for TSH release,
β = rate constant for TSH elimination,
Q₀= total amount of TSH released after TRH,
V = distribution volume of released TSH,
C₀ = plasma TSH concentration at time of zero.
Based on the results of TRH stimulation tests, the values of parameters α, β and Q₀/V were estimated by non-linear least-square methods and the regression curves indicating the time course of Plasma TSH were obtained. The apparent fit of data to the regression curves was reasonable and the multiple correlation coefficients were satisfactory.
The normal ranges for the parameters α, β and Q₀/V were 4.46 to 13.07 hr^-1, 0.63 to 1.30 hr^-1, and 6.7 to 19.7 μU/ml plasma respectively. A slight increase of Q₀ /V was observed in patients with simple goiter and euthyroid chronic thyroiditis. Markedly increased Q₀/V and decreased a were characteristic of patients with typical hypothyroidism, and decreased β was also observed in some patients. On the other hand, a marked increase of Q₀/V was the only finding in patients in transient hypothyroid state. Moderate increases of Q₀/V and definite decreases of α were observed in more than half of the patients with pituitary drawfism and seemed to be the cause of the delayed response.
The above results indicate that the mathematical model applied here is useful enough for quantitative analysis of the plasma TSH dynamics after TRH stimulation.

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