It is well-known fact that hormonal therapy has been applied to hormonedependent cancer. Androgenic derivatives have been used for long time as an effective agent. The mechanism of anti-tumor action of androgens, however, has not been fully clarified. It is conceivable that there is some discrepancy between the hormonal activity and anti-tumor activity. We tried to find out the steroids having a stronger anti-mammary-tumor activity without hormonal potency. A screening test for anti-tumor activity was performed with a series of diosphenol steroids, and many of them were found to be effective. 2, 17β-Dihydroxy-4, 4-dimethylandrosta-1, 5-dien-3-one was selected as a suitable anti-tumor agent for clinical use because of the highest potency and absense of hormonal side effects. Clinically, 4 out of 20 patients with advanced breast cancer acquired objective remission. The absence of any side effect was confirmed in the clinical trials. The compound is promising for clinical use.

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The developmental interrelationship between the neurosecretory pathway and the hypophysial portal system has been lightmicroscopically studied in young rats. On the first day after birth, AF-positive neurosecretory substance appeared in the supraoptic nucleus, but not in the paraventricular nucleus, where it appeared four days later. On the 4th day of postnatal life, the primary plexus of the hypophysial portal vessels began to penetrate the external layer of the median eminence from the supratuberal plexus. At the same time, few delicate fibers containing AF-positive materials were detected in the intermediate layer of the median eminence, but not in the posterior lobe. Occasionally they deviated from the main route, i. e., the hypothalamo-hypophysial tract in the intermediate layer, and entered the external layer. On the other hand, nerve fibers demonstrated by silver impregnation (Palmgren, 1948) were traced from the intermediate layer into the posterior lobe via the pituitary stalk. Several days later, the capillary loops penetrated deeply into the external layer of the median eminence. Some of them reached the intermediate layer and established contact with the AF-positive neurosecretory fibers. Subsequently, the AF-positive neurosecretory fibers increased in number within the intermediate layer of the median eminence, and primary capillary loops of the portal vessels developed into their adult form. At days 9 and 10 after birth AFpositive neurosecretory fibers appeared within the posterior lobe.

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For 10 years from 1955 to 1964, 415 cases of hyperthyroidism were treated with I131 and the existing status could be traced in 285 of them. Among these cases, 85.6% were euthyroid, 8.4% hypothyroid, and 6.0% still hyperthyroid. The incidence of hypothyroidism increased relative to the passage of years after treatment. The relatively low incidence of hypothyroidism in this series, compared with the reports from Western countries, is probably due to the relatively low dose of I131 used in each treatment. The high content of iodine in the Japanese diet might have some relationship to this low incidence. No incidence of thyroid tumor or leukemia was observed in these patients. No abnormalities were observed in 41 children born from 27 patients after I¹³¹ treatment.

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It has been questioned whether the human chorionic gonadotropin (HCG) could form the specific precipitate with its antiserum or not. To clarify this point directly, the absorbed rabbit anti-HCG serum which showed only one precipitin band to HCG preparation and no band to human serum or child urine protein, was incubated with partially purified HCG at 37°C for 60 minutes and then refrigerated at 4°C for four days. The resulting precipitate was completely washed until no HCG activity was shown in the supernatant and placed in glycine-HCl buffer (pH2.5, 0.167M), and then passed through a Sephadex G-100. The immunologically and biologically active HCG was dissociated from the specific precipitate and fractionated apart from the rabbit 7Sr-globulin. This result was a direct proof that HCG could produce the precipitating antibody in immunized rabbit.

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The metabolism of progesterone in the feto-placental unit in vitro was studied. Homogenates of four fetal livers (after 22-28 weeks gestation) were incubated with progesterone-4-¹⁴C with an NADPH generating system, and a large amount of 20α-hydroxypregn-4-en-3-one and smaller amounts of 5β-Apregnane-3α-o1-20-one and 5β-pregnane-3α, 20α-diol were identified. It is therefore considered that the major pathway of progesterone metabolism was: progesterone→20α-hydroxypregn-4-en-3-one, and that the activity of Δ4-3-keto steroid hydrogenase in fetal liver was significantly lower than after birth. The conversion of 20α-hydroxypregn-4-en-3-one to progesterone was shown to take place in vitro in a homogenate of human placenta with added NADP. These results suggest that the interconversion of progesterone and 20α-hydroxypregn-4-en-3-one occurs in the feto-placental unit, permitting the reutilization of progesterone which is indispensable for maintenance of pregnancy.

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The amount of neurosecretory material (NSM) in the median eminence (ME) and the morphological changes in NSM of the supraoptic nuclei were investigated over a 24-hour period in Japanese quails, which were held on 8-hour daily photoperiods from 37 days to 55 days of age and then subjected to continuous illumination for 32 hours before sacrifice. Daily rhythmic changes were found in the amount and the concentration of NSM in ME, as well as in the volume of the stainable portion of ME. The rhythmic changes of the concentration of NSM in ME was inversely related to that of the volume of the stainable portion of ME. These rhythms in ME as well as in the morphological observation of NSM in the supraoptic nuclei suggest that the onsets of light and dark periods activate the hypothalamic neurosecretory system resulting in the initiation of synthesis and release of NSM. Biological meanings of these phenomena are discussed in relation to the avian gonadal growth induced by photoperiodical manipulation.

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In an attempt to develop a clinical test for thyrocalcitonin function, the recovery from hypercalcemia induced by an intravenous injection of 0.4ml per kg body weight of 8.5% calcium gluconate was evaluated through serum calcium determination before, immediately after, and 1, 2, and 3 hours after the injection. Approximate Expected Time of Recovery (AETR) averaging 5.4±0.4 hours (S. E.) in 25 normal subjects ranging in age from 17 to 72 years showed a significant positive correlation with age (P<0.05). AETR was not significantly different from normal in 10 cases of postoperative hypoparathyroidism, 6.5±0.8 hours, and 6 cases of hyperventilation tetany, 7.6±1.0 hours, while it was significantly shortened in 3 cases of idiopathic hypoparathyroidism and 4 cases of euthyroid goiter.

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Perfusions of the human term placenta with radioactive androstenedione, testosterone, DHEA, progesterone, cholesterol and estradiol-17β as precursors were carried out and the formation of estrogens was investigated. After perfusion for three hours with human whole blood, added with human chorionic gonadotropin and cofactors, radioactive metabolites in the perfusate were studied. The radioactive metabolites were purified by chromatography at each step of purification. Estrogens were measured by the Kober reaction, and the radioactivity was counted by the gas flow counter. These experiments demonstrated that C-19 steroids were aromatized in a high yield by the perfused human placenta to estrone and estradiol-17β in the ratio of approximately 3 to 1, but that it was not capable of converting androgens to estriol. It was also noted that there was no conversion of estradiol-17β to estriol. In the perfusion study with DHEA, which is considered to be an important intermediate to estriol in the feto-placental unit during pregnancy, 10.7% of the initial radioactivity was recovered as a polar phenolic compound which behaved like 16-epiestriol on preliminary identification. Furthermore, neither progesterone nor cholesterol converted to estrogens in the human perfused placenta.

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Human ovaries were obtained from two normally menstruating women who had received PMS and HCG before the operation and biosynthesis of estrogen was investigated with a perfusion technique. As substrates, progesterone-4-¹⁴C and androstenedione-4-¹⁴C were added into the perfusate. The phenolic fraction of the extract of the perfusate was purified by gradient elution partition chromatography on a Celite column and paper chromatography. Throughout these purification steps, the radioactive metabolite in the estradiol fraction behaved exactly as the carrier estradiol. The conversion rate of progesterone into estradiol was 1.5% and that of androstenedione was 4.7%. The advantages of a perfusion experiment for the study of biosynthesis and metabolism of estrogen were discussed.

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The influence of three corticoid-inhibitors (Amphenone, Metopirone and SU 9055) on the corticoid secretion of the domestic pigeon was studied on a comparative basis. The level of corticosterone was reduced considerably with Amphenone and Metopirone; SU 9055 induced a rise. The cortisol (?) level was reduced moderately with the three inhibitors. The findings on corticosterone only were statistically significant. The implications of these results have been briefly discussed.

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Adrenal and liver tissues from a human fetus aborted after 6 months' gestation were sliced to 30μ thickness and incubated with dehydroepiandrosterone-4-¹⁴C in Krebs-Ringer bicarbonate buffer solution. 16αOH DHEA was found in the adrenal incubate after purification by alumina column chromatography, acetylation, thin layer chromatography and recrystallization to constant specific activity. The recrystallization data indicated that 4.9% of the radioactive material in the initial extract was 16αOH DHEA. However, the radioactive material in the androstenetriol fraction of the initial extract was not associated with carrier androstenetriol. Androstenetriol was detected in the liver incubate after purification by alumina column chromatography, two successive thin layer chromatographies and recrystallization to constant specific activity. The recrystallization data showed that 5.6% of the radioactive material in the initial extract was androstenetriol. But the radioactive material in the 16αOH DHEA fraction of the initial extract was dissociated from carrier 16αOH DHEA. The possible role of the fetus in the formation of estriol during pregnancy is discussed.

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