Labelled dehydroepiandrosterone and androstenedione were injected into the umbilical vein at cesarean section in the mid trimester, and the formation of estrogens in the feto-placental compartments was investigated. Estrone, estradiol-7β and estriol were formed in this system of these precursors. Radioactive estriol found in the fetal liver was higher in concentration than that in the cord blood or placenta. Estriol was formed from dehydroepiandrosterone more efficiently than androstenedione in the feto-placental unit.The conversion rate to estriol in the maternal urine well correlated with the ratio of estriol formed in the cord blood.Estrogen metabolism during pregnancy was also discussed.

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An electron microscopical observation was made on the adrenal cortex of rats under hyper-and hypofunctional experiments. Such stimulative factors as administration of ACTH, unilateral adrenalectomy and injection of snake toxin were noted to commonly dilate the anastomosing tubules of the agranular endoplasmic reticula (ER) in the fasciculata cells throughout their length. Furthermore these factors diminished quickly the number of fat droplets. On the other hand, prevention of the pituitary ACTH release due to hypophysectomy induced retrogression of the tubular ER, storage of the fat droplet and destruction of the mitochondria in the atrophic fasciculata cells. The osmiophilic substance was deposited initially in the confluences of anastomosing tubular ER and grew thereafter into the fat droplet. The probable reason for the rapid loss of fat droplets from the stimulated cells is that the content of fat droplets is transported through the tubular ER. However, in deficiency of the circulating ACTH, fat droplets were stabilized without movement on account of atrophy of the ER. In fact, they increased in number and in size. Elevated ACTH levels resulted in an approximation of the ER to the mitochondria, and the limiting membrane of ER was often adhesive to the external membrane of mitochondria. This topographic connection is favourable to our views that biosynthesis of steroid hormones would be carried out in the lumen of the anastomosing canalicular ER in participation with the enzymes laden on the membranes of mitochondria and ER. The final product of these duct systems seemed to be discharged into the intercellular space, because there was evidence that the terminals of the tubular ER opened into the intercellular space under hyperfunctional conditions.

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Plasma renin activity in the peripheral blood was assayed in 50 patients with various types of hypertension including 3 cases of primary aldosteronism and was compared with the values obtained from 28 normal controls.Also changes in the pattern of plasma renin acitivities due to a sodium restricted diet were investigated with concurrent estimation of urinary aldosterone in some of these subjects and a patient with Addison's disease.The results confirmed that the determination of plasma renin activity is a useful aid in diagnosing hypertension with renovascular involvement and primary aldosteronism. The response of plasma renin acitivity to a sodium restricted diet was essentially the same in normotensive subjects and patients with essential hypertension.In renovascular hypertension plasma renin activity was significantly high (P<0.001) but the responses to a sodium restricted diet were not so pronounced when expressed as the ratio of response to initial activity.In all with primary aldosteronism no significant rise in plasma renin activity was found with a sodium restricted diet, but it increased significantly in a patient with Addison's disease.

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An attempt has been made to produce experimental cancer in the prostate of Wistar strain male rats by local administration of 20-methylcholanthrene (MC), thereby evaluating the incidence of neoplasmas, changes in activities of LDH and ALP, DNA metabolism and in the LDH isozymes pattern as well as the influence of sex hormones upon them. The following are the results obtained: 1) While estradiol benzoate (Eb) increased the incidence of prostatic neoplasmas, testosterone propionate (Tp) inhibited it. 2) DNA metabolism, especially the tritium index, was stimulated by Eb, whereas it was inhibited by Tp. 3) LDH activity was inhibited by Eb and promoted by Tp.As for the effects on the LDH isozymes pattern, Eb decreased the proportion of the M type, while Tp increased it. 4) ALP activity was somewhat suppressed by Eb administration.

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Liver, adrenal, kidney, spleen, lung and brain samples (1.0g or 0.5g) from human fetuses (5 months, 6 months and 7 months) were sliced and incubated for 90 mins. with pregnenolone-³H. 16α-Hydroxypregnenolone formed was tentatively identified, since it had a constant specific radioactivity on repeated chromatographies. Per cent conversions of pregnenolone to 16α-hydroxypregnenolone were 36.8% to 13.7% for liver slices, 0.96% to 0.57% for adrenal slices, and less than 0.05% for kidney, spleen, lung and brain slices. Urinary excretion of 16α-hydroxypregnenolone was much greater than pregnenediol and pregnenolone in newborn boys but adrenal concentration of 16α-hydroxypregnenolone was much less than pregnenolone in autopsied newborns. From the data, it seems that pregnenolone synthesized by the fetal adrenal is hydroxylated at 16α-position mainly in the liver and partly in the adrenal.

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After X-irradiation, the testicular weight of mice (6 weeks in age) decreased gradually, being significantly reduced on the 14th day post-irradiation and thereafter, in comparison to the control group.The specific activity of the 17α-hydroxylase in the testicular homogenate of the X-irradiated mice became higher than in the non-irradiated animals.When testes of the rats were locally X-irradiated, the weight of testes decreased almost half, but the weight of accessory organs remained almost unchanged.However, further detailed analysis of the individual enzymes of rat related to biosynthesis of androgens revealed that the 17α-hydroxylase and the 17α-hydroxypregnene C₁₇-C₂₀ lyase activities per testis were significantly reduced by local X-irradiation, while the Δ⁵-3β-hydroxysteroid dehydrogenase activity coupled with the isomerase was somewhat enhanced by this treatment. By administration of human chorionic gonadotrophin to the locally X-irradiated rats, the enzyme activities related to testosterone formation except 17β-hydroxysteroid dehydrogenase were stimulated, in accordance with the increased weight of accessory organs by the gonadotrophin. From the results that the specific activities of the enzymes related to androgen production were higher in X-irradiated than in the control, and that those activities were stimulated by the gonadotrophin in parallel with histological observation on proliferation of interstitial cells, the enzymes related to testosterone production from pregnenolone were intercellularly located to the interstitial cells and intracellularly to their microsomes.

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The effect of estradiol-17β on the metabolism of phosphatidylethanolamine phosphatidylcholine in rat uterus was investigated in vitro by using 32Porthophosphate, 32P-phosphorylethanolamine, ³²P-phosphorylcholine, ³²Pphosphatidylethanolamine and ³²P-phosphatidylcholine as substrates.1.It was suggested that the biosynthesis of phosphorylethanolamine, phosphorylcholine, phosphatidylethanolamine and phosphatidylcholine was stimulated by estradiol-treatment.2.The incorporation of ³²P-phosphorylethanolamine into phosphatidylethanolamine was increased but that of ³²P-phosphorylcholine into phosphatidylcholine was not increased by the administration of estradiol-17β.The incorporation of phosphatidylethanolamine into phosphatidylcholine not affected by estradiol-17β and the reaction from phosphatidylcholine phosphatidylethanolamine was not observed.

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The concentration of free estrogen in 1ml of fractionated plasma obtained from the ovarian venous blood of rats showing a regular 4-day cycle was determined by a bioassay method based on 2, 3, 5-triphenyltetrazolium chloride reduction in the mouse vagina.A significant amount of estrogen, 0.2ng/ml plasma of estradiol equivalent, wasdetected in the ovarian venous blood plasma during diestrus Day 1 and on the morning of diestrus Day 2.The estrogen level markedly elevated in the afternoon of diestrus Day 2 and continued to rise up to a peak (4.5ng/ml) before noon of proestrus.The highly elevated estrogen level sharply declined about 10hrs.prior to ovulation when LH was supposedly released from the pituitary.No significant increase of estrogen level was seen thereafter until diestrus Day 2 of the next cycle.A sharpdecline of ovarian venous blood estrogen to the level of diestrus was induced within 3 hrs.after removal of the pituitary in the afternoon of proestrus when estrogen secretion was highly stimulated.Intravenous injection of gonadotropin, 250μg of NIH-FSH-S₁ or NI.H-LH-S₃, caused a significant stimulation of the ovarian estrogen secretion in the rat hypophysectomized at proestrus.The mechanisms controlling the ovarian estrogen secretion in the rat were discussed.

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Activities of NADPH-cytochrome c reductase, NADPH-dichlorophenolindophenol diaphorase and glucose-6-phosphate dehydrogenase in the anterior pituitary and in the liver were compared in normal and in thyroidectomized rats, with or without thyroxine (T₄) supplement. Responses of pituitary enzymes to thyroidectomy and T₄ supplement were different from, in some cases even opposite to, those of the same liver enzymes. The typical response was observed in glucose-6-phosphate dehydrogenase; the enzyme activity in the pituitary increased by thyroidectomy and the increased activity was suppressed by T₄ supplement, whereas the activity in the liver decreased by thyroidectomy and increased by T₄ treatment. The mechanisms and the physiological significance of these findings were discussed in connection with protein synthesis in the two tissues.

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Female rats receiving injections of estrone for the first 20 days of postnatal life, 25μg for the first 10 days and 50μg for the next 10 days, were ovariectomized at 77-97 days of age and those given injections of testosterone propionate for 30 neonatal days, 0.5mg for the first 10 days 1.0mg for the middle 10 days and 2.0mg for the last 10 days, were ovariectomized at 161-167 days. These animals received injections of 20 or 100μg estrone for 3 weeks, from the 22nd postoperative day on. Ovariectomized adult rats given no neonatal steroid treatment also received similar estrone injections for a 3-week period. When the rats were sacrificed on the day following the last injection, increase in uterine weight was less marked in animals given neonatal injections of the sex steroid than in the controls. Following the estrone injections for 3 weeks, areas undergoing hyperplasia and squamous metaplasia were found in the uterine epithelium in all the rats receiving neonatal steroid injections, the changes being most marked in the cervical region. The control rats exhibited no such changes in the uterine epithelim.

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Adult female rats were rendered anovulatory by continuous illumination. Pituitary LH of these constant estrous rats decreased with the time length of illumination. Acidic extract from the rat hypothalamus was injected into these rats through the carotid artery for testing LH-RF activity. The extract, if a dose more than 2 hypothalamic fragments per rat was given, induced ovulation. Ovulatory response was determined by observation of tubal ova and formation of new corpora lutea. Cerebral cortical extract, lysine vasopressin and oxytocin were not active in stimulation of ovulation. Pituitary LH and plasma LH shortly after intracarotid injection of the hypothalamic extract were estimated by the OAAD method. A single injection produced a transient rise in pituitary LH, and the maximum occurred 20 mins. after injection. Sixty mins. after injection pituitary LH showed a significant decrease. Corresponding to this fall in pituitary LH, plasma LH showed a significant rise. Both pituitary LH and plasma LH returned to near-initial levels 4 hrs. after injection. These results suggest that hypothalamic extract may stimulate the sysnthesis of LH by the anterior pituitary of constant estrous rat as well as the release of LH.

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A new modification of the ovarian ascorbic acid depletion assay has been devised using adult pseudopregnant rats of the Wistar strain. The sample to be assessed for LH activity is injected in a volume of 0.005ml, directly into the ovarian bursa. Minimum effective doses of HCG and LH (NIH-LH-S5) averaged 0.005 I. U. and 0.005μg, respectively. Indices of precision were (lambdas) 0.18 for HCG and 0.12 for LH. The principal shortcoming lies in the fact that LH concentrations less than 1μg/ml cannot be detected, because of the volume restriction. This method, however, is useful particularly if only a small amount of material is available for assay.

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Na-sulfaacetylthiazole, 0.5g/kg body weight, was injected into immature and adult rats to produce obstructive nephropathy. Necrotic changes in the myocardium were found in all of the 9 adult rats of about 120 days of age, whereas no such changes occured in immature animals of about 40days of age. Thyrocalcitonin, 50mMRC units a day injected subcutaneously for one week, completely inhibited the occurrence of such myocardial lesion in adult animals, as did parathyroidectomy performed one week previously. Serum calcium was decreased from the normal adult level in thyrocalcitonin treated or parathyroidectomized animals but not in untreated immature rats. Thyrocalcitonin appears to have some effect on cardiovascular system in addition to the known effect on the bone.

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Blood pH, blood levels of Ca, P and protein were measured in 5 patients with thyroid diseases during and after the surgical maneuver of the gland and compared with those in a patient with a cervical cyst located between the anterior neck muscles who underwent a similar neck operation but without direct intervention into the thyroid. Immediately after the surgical handling of the thyroid, a statistically significant fall in the blood Ca level ensued that reached the lowest point within 1hour and recovered by 3hrs. Such a remarkable change was not observed with regard to the blood pH and the blood level of P and protein. The blood Ca level was maintained at the preoperative level, on the other hand, in the patient whose thyroid was not operated on. From these results a possibility was considered that the thyrocalcitonin leaked out of the damaged thyroid caused this hypocalcemia.

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