White, for many synthetic progestins, the oral route is the preferred mode of administration, naturally occuring steroid, progesterone, is poorly active when given by mouth. Absorbed pogesterone reaches the liver first before entering into the systemic circulation and this inactivation of progesterone has been believed to occur in the liver. In this experiment, the possibility of the structural changes of progesterone in the small intestine was studied.
Methods were similar to those in the previous experiment. After an injection of radioactive progesterone into the samll intestine, the mesenterial venous blood was collected and analyzed. In this experiment, the doses administered varied form 4 mg to 10 mg.
Blood extracts were first analyzed by alumina column chromatography. Several examples of the column chromatogarphic elution patterns are shown in Fig. 1 and Fig.3. progesterone was isolated and identified in 5 of 6 cases. The identification was based on the chromatographic mobilities, ultraviolet absorption and sulfuric acid chromogen spectrum. The radiochemical homogeneity of the recovered progesterone diluted with cold progesterone is shown in Fig. 2. 20-Hydroxy-4-pregnene-3-one was isolated and identified. in 3 of 6 cases. The identification was bases on the chromatogarphic mobilities and chemical natures of the derivatives. Chemical reactions used for the identification are illustrated in Fig.4.
From the experimental data summarized in Table 1, it was found that when large doses of progesterone were administered, free steroid in the mesenterial venous blood was increased and the metabolizing ability of progesterone in rabbit intestine was markedly different from case to case. The influence of bile salts on the absorption of progesterone from the small intestine is now under investigation.

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In the privious experiments, Δ^{4, 6}-9β, 10α-pregnadiene-20α-ol-3-one was isolated from human urine after administration of 6-dehydro-retro-progesterone. And the incubation experiment with rabbit liver homogenate also demonstrated the conversion of this compound into its 20-reduced material. In the latter experiments, however, a large proportion of 6-dehydre-retroprogesterone was converted into an unknown material (Compound X).
In this experiment, 6-dehydro-retroprogesterone was administered to rabbits and the urinary matebolites were isolated and partly identified. Billiary excretion of the compound was also examined.
Urines were collected from rabbits which received 6.7 mg of tritium labeled 6-dehydro-retroprogesterone (containing 20.1μc ³H) and from rabbits which received 100-200 mg of the cold compound. Daily excretion of radioactivities is presented in Fig. 1. Three-day urines were collected from two groups of rabbits and were used for further study. The method of extraction is indicated in Table 1. A large proportion of urinary radioactivities was found to be conjugated with glucuronic acid as indicated in Table 2. These extracts were chromatographed on alumina and the elution patterns are illustrated in Fig. 2 and Fig. 3. The compound eluted with 0.3% methanol in benzene was identical with Δ^{4, 6}-98, 10α-pregnadiene-20α-ol-3-one in the paper chromatographic moblities, sulfuric acid chromogn spectrum and UV absorption spectrum. This compound was easily acetylated with acetic anhydride and pyridine, and easily oxidized with aqueous chromic acid. The latter product was identified as 6-dehydro-retroprogesterone from the chromatographic mobility and spectral analysis. These data confirmed the identity of the original compound as ^{4, 6}-98-10α-pregnadiene-20α-ol-3-one.
The compoudd eluted with 1% and 5% methanol in benzene was chromatographed on paper in Bush B5 system and two radioactive peaks, A and B, were observed. After repeated paper chromatography, UV absorption spectrum of these compounds were examined in methanol. Both of these compounds showed an absorption maximum at 285 mμ, in methanol indicating the presence of ^{4, 6}-3-one structure in these molecules. Compound B was, however, found to be contaminated by some impurities.
Billiary excetion of radioactivities after intravenous administration of 6-dehydto-retro-progesterone is shown Fig.6. ^{4, 6}-9β, 10α-pregnadiene-20α-ol-3-one was also isolated from the bile specimens. The Compound X obtained in the previous incubation experiment was not found in this study. The compound might be an artifact or an intermediate metabolite between 6-dehydro-retroprogesterone and Compound A or B.

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The effects of pancreatectomy, hypophysectomy, adrenalectomy on NADP-isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, NADH-cytochrome C reductase, NADPH-cytochrome C reductase, pyridine nucleotide transhydrogenase, glutathione reductase and acetyl CoA carboxylase in rat liver were studied, and compared with those of replacement of insulin, ACTH, glucocorticoid respectively. On the other hand, oxidative phosphorylations of liver mitochondria from hypophysectomized and adrenalectomized rat have been observed with the use of succinate as substrate.
Results and discussion :
1) The activities of isocitrate dehydrogenase, NADH-cytochrome C reductase, NADPH-cytochrome C reductase, pyridine nucleotide transhydrogenase and acetyl CoA carboxylase decreased when pancreas was removed subtotally, but the activities recovered to normal when insulin was replaced to subtotal pancreatectomized rats. On the contrary the activity of glucose-6-phosphate dehydrogenase increased after pancreatectomy and further more increased activity was observed when insulin administered to pancreatectomized rats.
2) The activities of isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, NADH-cytochrome C reductase, glutathione reductase obviously increased after hypophysectomy or adrenalectomy, and returned to normal after administration of ACTH, glucocorticoid to these rats. But a fall in activities of NADPH-cytochrome C reductase, acetyl CoA carboxylase was obtained following hypophysectomy or adrenalectomy and recovered to normal when ACTH, glucocorticoid replaced respectively.
3) ADP/O for hypophysectomized or adrenalectomized rat liver mitochondria was found to be lower than that of control and recovered to normal after respective replacement of ACTH and glucocorticoid.
4) From the point of view that phosphate potential (ADP/ATP) regulates the carbohydrate and lipid metabolism in the cell, and from obtained results, glucocorticoid may have a physiological function to decrease the extra-oxidation of carbohydrate and lipid by maintaining the efficiency of oxidative phosphorylation in mitochondria. On the other hand, insulin perhaps activates the metabolic activity of TCA cycle and it results in increased ATP formation in mitochondria with the help of glucocorticoid.
Insulin and glucocorticoid may accelerate ATP formation in mitochondria samely, but the difference between these two hormones is perhaps the former accelerates the conversion of mitochondrial high energy compound to extramitochondrial subcellular fraction and then promote the energy utilization for every de novo synthesis performed in the extramitochndrial cellular fraction, but the latter not always helps towards all synthetizing processes carried out in the cell.
5) The mentioned observation of acetyl Co. A carboxylase activities in several conditions may suggest that one of physiological function of glucocorticoid is to promote the first step of fatty acid de novo synthesis in liver, at least when pancreas is intact.

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Previously, it was reported that the Melanocyte Stimulating Hormone-like Substance in the urine of patients with retinopigmentosis (Patient Urinary MSH) had neither melanocyte-expanding action nor other physiological actions, differing from that in normal persons (Normal Urinary MSH). It was also observed that in the chemical structure of Patient Urinary MSH, methionine residue was in the form of methionine sulfoxide.
In the present paper, several effects of the Patient Urinary MSH and the Normal Urinary MSH were compared on some inorganic substances connected with the etiology of Retinitis Pigmentosa.
The results were as follow :
1) The Normal Urinary MSH caused swelling of rat liver mitochondria, but the Patient Urinary MSH lacked this tendency.
2) The uptake of Ca in rat liver mitochondria was inhibited by the Normal Urinary MSH, but the Patient Urinary MSH had little effect.
3) The Normal Urinary MSH lowered the level of Ca in rabbit serum, but the Patient Urinary MSH had no effect.
4) The Normal Urinary MSH decreased remarkably serum Fe levels of the normal rabbit and of the incipient stage rabbit of experimental Retinitis Pigmentosa, but the Patient Urinary MSH had a weak tendency. The serum Fe level of rabbit was increased by the experimental Retinitis Pigmentosa treatment.
5) The Normal Urinary MSH had no effect on the reduced glutathione content of rabbit blood.
Based on the results of the aforementioned experiments, a few considerations were made on the etiology of Retinitis Pigmentosa.

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Previous experiments have revealed that Melanocyte Stimulating Hormone (MSH) augmented the activity of tyrosinase, and the Urinary MSH-like Substance of Retinitis Pigmentosa Patient (Patient Urinary MSH) differed from the Urinary MSH-like Substance of normal persons (Normal Urinary MSH) on various physiological actions.
This report deals with the effects of the MSH and the MSH-like Substances on three tyrosine metabolic pathways : (1) tyrosine→p-hydroxyphenylpyruvic acid→homogentisic acid→fumaric acid (2) DOPA → Dopamine → adrenaline (3) tyrosine → diiodotyrosine → thyroxine.
It was designed to investigate the difference of the Urinary MSH from patient and normal adult in these actions.
Warburg's manometric method was employed for the study of the pathway (1) and (2). For the study of the pathway (3), the radioactive iodide (¹³¹I) was used as a tracer in the formation of diiodotyrosine.
The results were as follows : Though the MSH and the Normal Urinary MSH suppressed the tyrosine metabolism in the pathway (1) and the DOPA decarboxylation in the pathway (2), the Patient Urinary MSH lacked in this tendency. The formation of diiodotyrosine in the pathway (3) was stimulated by the MSH and the Normal Urinary MSH, but was not by the Patient Urinary MSH.
It was suggested from these results that the MSH stimulates the melanin synthesis by affecting the tyrosine metabolism, and the Patient Urinary MSH is different from the Normal Urinary MSH in the properties related to these actions.

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For the purpose of examining the estrogen metabolism in pregnancy and the effects of human chorionic gonadotropin (HCG) exerted on it, the amount of free estrogen contained in the human chorionic tissues was measured successively each month by using the Brown-Kanbegawa method as the method of quantitative determination and paper-chroma-tography as the method of identification.
At the same time, an experiment was made on the incubation of the chorionic tissues in the initial and final stages under the aerobic and anaerobic conditions. The results are as fallows :
(1) The amount of free estrogen contained in the chorionic tissues increased along with the progress of pregnancy, with the increase of estriol being especially prominent. Also, the possibility was noted that 16-epiestriol exists in the chorionic tissues in the final stages of pregnancy.
(2) In the incubation experiment of the chorionic tissues, the total estrogen amount was found to reach a high value under an anaerobic condition when the incubation was carried out with estrone, estradiol-17β or estriol as the substrate. The interconversion of estrone and estradiol-17β was observed both under the aerobic and anaerobic conditions, while, under anaerobic conditions, estrone was seen to be easily liable conversion into estradiol-17β, although estradiol-17β showed that it could not easily be converted into estrone, conversion of estrone and estradiol-17β into estriol could not be observed.
No extraordinary findings were noted with the media in the case of incubation with the addition of HCG.
(3) Conversion into estrone or estradiol-17β from Δ⁴ androstene-3, 17-dione and dehydroepiandrosterone and testosterone was noted under aerobic conditions, with the chorionic tissues in the final stages indicating a value higher than that in the initial stage. In the case when HCG was added among the media, as compared with the case when it was not, the rate of conversion from Δ⁴ androstene-3. 17-dione into estrone and the rate of conversion from dehydroepiandrosterone and testosterone into estrone and estradiol-17β, indicated higher values while conversion from those substrata into estriol was not noted.
Also, no conversion was seen from 19-nortestosterone, pregnenolone, 17α-hydroxy-pregnenolone and 1 7α-hydroxyprogesterone into estrogen.
Also, the chorionic tissues in the final stage were incubated aerobically with 17α-me-thyltestosterone as substrate, and, as a result, a metabolite assumable to be 17α-methy-lestradiol was obtained.

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Male albino rats fed more than 400 days with a newly devised high fat diet exhibited impaired carbohydrate metabolism.
The metabolic alteration in these rats was studied, and compared with rats fed a normal diet or a high protein diet.
1) Rats fed with a high fat diet became obese. On the 400th day body weight of the high fat diet group was around 430 g, in contrast to 240 g of the normal diet group and 300 g of the high protein diet group.
2) Rats fed with a high fat diet exhibited disturbed glucose tolerance test and insulin sensitivity test, while, rats with a normal diet or high protein diet had normal glucose tolerance test and insulin sensitivity test.
3) According to our experiments in high fat diet rats, increased gluconeogenesis and impaired glycolysis were observed. And, the mechanism of disturbed carbohydrate metabolism in high fat diet was proposed as shown in the following figure.
4) The relationship between pathogenesis of high fat diet and glucose-fatty acsd cycle was discussed.

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