TRH test and T₃ suppression test were performed on patients with Graves' disease who underwent subtotal thyroidectomy after treatment with antithyroid drugs for 2.5-5 months. On 43 of the patients, TRH test was performed before, 1 week after and 1-2 months after surgery and T₃ suppression test was also performed in 1-2 months post-operative period. For other 3 groups of the patients TRH test was performed at 2-6 months, 6-12 months, 12-24 months and 24-41 months after sugery, and T₃ suppression test was also performed just after each TRH test. As to TRH test, the response was defined as positive when basal TSH value was less than 2. 0 μU/ml and peak value was more than 6. 2 μU/ml or the difference between basal TSH and peak TSH value was over 5 μU/ml following TRH (500 μg) injection. T₃ suppression test was performed by measuring the 24-hr thyroidal uptake of radioiodine after daily administration of 75 μg of T₃ for 8 days. The response was defined as positive when the value for 24-hr uptake after T₃ administration was less than half of the control value.
The results were as follows;
(1) In 11 of 43 patients, response to TRH test already changed to positive 1 week after operation and in 21 of 43 patients TRH test changes to positive 1-2 months after operation.
(2) In general, response to TRH test changed to positive earlier than response to T₃ suppression test.
(3) T₃ suppression test in 1-2 months after operation was useful to evaluate prognosis.
(4) A half of the positive respondents to TRH test showed exaggerated response.
(5) Basal TSH value of positive respondents to TRH test was 9. 27±1. 81 μU/ml (mean±SE) which exceeded the normal range.
(6) Some patients showed negative response to conventional T₃ suppression test despite of their high basal TSH value. This might be due to the insufficient dose of T₃ to suppress TSH.
(7) Concerning patients whose serum T₃-RU, T₄, T₃ and TSH were within normal limit after subtotal thyroidectomy, 80% of them showed correspondance in the results of TRH test and T₃ suppression test.

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Crude gonadotropins extracted from the urine of patients with chorioepithelioma (choriocarcinoma) by Bradbury method was purified by a combination of Sephadex gel filtration, CM-C and DEAE-C chromatography.
Two biologically active fractions (fraction t-hCG-A and fraction t-hCG-C) were obtained. The former cross-reacted with anti-hCG sera and the latter cross-reacted with anti-hCFSH sera in experiments with Ouchterlony immunodiffusion and immunoelectrophoresis. But the hCG or hCFSH from normal pregnancy and t-hCG-C from choriocarcinoma were different in their potency of being adsorbed on ion-exchange cellulose respectively. T-hCG-C was poorer in aspartic acid and glycine, and richer in serine, threonine and tyrosin to which carbohydrates bind than hCFSH from normal pregnancy.
These two fractions contained high concentrations of carbohydrates, especially hexose and sialic acid, less concentration of hexosamine, compared to those of hCG and hCFSH obtained from urine of normal pregnant women.
Sera of normal pregnant women in the first and third trimester and those of patients with chorionic neoplasias were gel filtrated on a Sephadex G-100 upward flow column in the same conditions. Biological activity of hCG in sera of normal pregnant women was recognized in 2-3 peaks on the gel filtration, and the molecular weights of those were considered to be about 25,000-40,000. In case of sera of chorionic neoplasias, however, it was admitted as multi-peaks (the molecular weights : about 10,000-70,000). It might be one of the features of chorionic neoplasias that the biological activity was found even in fractions of molecular weight 10,000 on the gel filtration, and to pay attention to this phenomenon might be a useful sign for the diagnosis or the management of patients with chorionic neoplasias.
As a conclusion, all the above findings suggest that the molecular structure of t-hCG- A and t-hCG-C from choriocarcinoma differes from that of hCG and hCFSH from normal pregnancy respectively.

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Regulation of prolactin secretion in pituitary is considered to be mostly carried with the action of prolactin inhibiting factor in hypothalamus. We have investigated on the subject of prolactin releasing factor in the hypothalamus of rats in last stage of pregnancy using puerperal and ovariectomized rats as recipients.
After prepared the cell-free system of pregnant rat hypothalamus with sonic oscillator, supernatant was produced by ultracentrifuge (25,000 x g, 30 min.) and utilized for the experiments. When the extract was injected intramuscularly to puerperal rats (48-60 hours after delivery), serum prolactin values increased gradually to 3 times of control values, but pituitary prolactin values showed the variation with decrease and recovery. The control values were obtained by determination after injection of cerebral cortical extract to puerperal rats. After administration of a extract of non-pregnant rat hypothalamus to puerperal rats, serum prolactin values decreased and pituitary prolactin values increased antagonistically. In the ovariectomized rats pretreated with estradiol and progesterone, serum prolactin values increased in 1 hour after administration of the extract of pregnant rat hypothalamus, but pituitary prolactin values did not showed any variation.
The present experiment suggests that the prolactin secretion promoting factor exists in the hypothalamus of pregnant rats and predominates over as compared with PIF in last stage of pregnancy.

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The preoperative identification of adrenal tumor is essential to correct diagnosis and appropriate treatment. Adrenal venography is one of the most useful adjuncts for this purpose, but catheters of various types introduced in the past are not necessarily well configured to catheterize adrenal veins. The catheter newly designed by us made catheterization of the left adrenal vein much easier even for unskilled hands. Our new catheter has been used in 20 of 55 venographical studies which have been carried out in our service. Determination of cortisol concentrations in adrenal venous blood which was performed in 6 cases failed to give any clue to determine the laterality of the existing adrenal tumor.

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Norethindrone (ENT), which is a representative in estrane series of progestogen, is not only strongly progestational but also estrogenic and in some cases, antiestrogenic.
To understand progestational effect and antiestrogenic effect, the interactions of ENT on estrogen and progestogen receptors were studied in the uterine cytosol of white female rabbit. The 274,200 × G supernatant of uterine homogenate was used as cytosol. ³H-Estradiol, 3H-Progesterone, ³H-ENT or cold ENT were incubated with uterine cytosol at 4°C for 2 hours.
Results are as follows :
1. Sucrose gradient centrifugation [5-20% linear and 40,000 rpm (159,200 × G) for 16 hours at 4°C] :
ENT was bound to estrogen 8S receptor in immature rabbit uterus (Fig. 2 & 3), and to progestogen 8S receptor in estrogen primed rabbit uterus (Fig. 5).
2. Kinetic study, determined by dextran coated charcoal (0.001 % dextran and 0.1 % charcoal) : (1) In the uterine cytosol of immature rabbit, ³H-estradiol-receptor binding was observed with Kd≅3.6 × 10^-9M and it was revealed that ENT was a competitive inhibitor to this binding with Ki≅2.6 × 10^-6M, as in Fig. 6. (2) 8S component, obtained by centrifugation of uterine cytosol (Fig. 1) in estrogen primed rabbit, binds ³H-progesterone with Kd≅8.1 × 10^-10M and Bm (maximal binding sites) ≅5.0 × 10^-8M/ mg of protein, and ENT was a competitive inhibitor in this binding with Ki≅2.3 × 10^-9M (Fig. 7 & 8). ³H-ENT-8S binding was demonstrated with Kd≅1.1 × 10^-9M and Bm≅8.7 × 10^-8M/mg of cytosol protein (Fig. 8).
These results indicate : (a) ENT is bound to both estrogen and progestogen receptors in 8S macromolecules of uterine cytosol, (b) competitive inhibition of ENT to these bindings indicated that ENT is bound to these receptors at the steroid binding sites where estradiol and progesterone bind to, (c) ENT has much more affinity to progestogen receptor (Ki≅2.3 × 10^-9M) than to estrogen receptor (Ki≅2.6 × 10^-6M), (d) while ENT is bound to progestogen and estrogen receptors at the same time, Bm of ENT (8.7 × 10^-8M/ mg of cytosol protein) is more than Bm of progesterone (5.0 × 10^-9M/mg of cytosol protein), and Kd of ENT (1.1 × 10^-9M) was less than Ki of ENT (2.3 × 10^-9M) in the binding to progesterone-receptor.
Biologically, while ENT is bound to progestogen-receptor with high affinity and to estrogen receptor with low affinity, ENT is actually progestational in low dose and antiestrogenic in high dose but the anti-estrogenicity seems to be incomplete in vivo as ENT may be metabolized to a potent estrogenic compound, ethinyl estradiol.

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Estrogen priming increases uterine 8S macromolecule which binds progesterone specifically.
Progesterone-8S complex in the cytoplasm enters into nucleus and is bound to chromatin finally.
In this paper, the mode of nuclear translocation of steroid in exchange assay of receptor introduced by Anderson et al.1) 2), and the mode of binding to chromatin were studied on the progesterone-receptor complex in the uterus of estrogen primed female rabbit.
1. After intravenous administration of 200 μg progesterone into the estrogen primed immature rabbit, uterine nuclei were prepared by the method in Table 1. These nuclei were incubated with ³H-progesterone and cold steroids at 4°C for 30 minutes, and then washed with buffer A. The radioactivity of the nuclei was counted.
This experiment was performed at 4°C because progesterone receptor and chromatin were observed to be degraded at 37°C for 20 minutes.
The effect of cold steroids in vitro on the incorporation of ³H-progesterone into the uterine nuclei of rabbit pretreated with progesterone was found to be similar to their effect on progesterone-receptor binding in cytosol or chromatin (Fig. 1).
2. The effect of cold steroids on ³H-progesterone-receptor-chromatin triplex (Table 2 and Fig. 2) was examined. Once ³H-progesterone-receptor-chromatin triplex was formed, it was difficult to exchange ³H-progesterone to other steroids at 4°C.
These results (1 & 2) indicate that progesterone-receptor complex enters into nucleus and is bound to chromatin. Exchange of steroid may occur in the nuclear progesterone-receptor complex, which is free from the binding with chromatin.
And thus exchange assay cannot represent quantitative data on receptor content.
3. ³H-progesterone-8S or 5S complexes were obtained by 5-20% sucrose linear gradient centrifugation (Fig. 3). The same molar concentration of these complexes from estrogen primed or castrated rabbit uterus were incubated with primed uterine chromatin for 30 minutes. Then the chromatin was washed with buffer A and the radioactivity was counted.
It was shown in Fig. 4 that ³H-progesterone-8S complex was bound to chromatin much more tightly than ³H-progesterone-5S complex in preparations obtained from both castrated or primed uterine cytosols.
All these results indicate that 8S may be the biologically active form of the receptor.
4. ³H-progesterone uptake into uterine nuclei was observed in very limited amount following the injection into uterine artery. The radioactivity in nuclei decreased easily by washing with buffer A as in Fig. 5.
The small amount of residual radioactivity after washing, that is, very limited number of binding sites with high affinity is considered to be indicative of biologically active binding.

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A study was performed to observe serum TSH response following TRH injection (TRH test) in 79 cases of Graves' disease (male 23, female 56, aged 16-70 years old), before and during treatment by antithyroid drug, in a total of 244 occasions. Treatment was mostly the daily administration of methyl-mercaptoimidazole (MMI), and in one case of propylthiouracil (PTU). TRH test was conducted by i.v. administration of 500 μg synthetic TRH, and subsequent 6 blood drawing until 2 hours. Serum TSH was measured by radioimmunoassay in each serum, and serum T₄, T₃, RT₃U and cholesterol were measured in the serum before TRH injection. In some cases, the results of TRH test were compared with those of T₃ ¹³¹I thyroidal uptake suppression test, using the ¹³¹I uptake values at 20 min. and 24 hours.
Results were obtained as follows :
1) Some cases showed positive TRH test at the early stage of treatment when the patients were in eumetabolic states, while many patients showed no TSH response in spite of their long maintenance at eumetabolic states.
2) When both serum T⁴ and T³ were high, all cases showed no response of TSH. When serum T⁴ alone was high, all cases except one case showed no response; whereas when serum T³ alone was high, 5 cases showed normal response. When both serum T⁴ and T³ were below normal, 2 cases showed no response. When serum T⁴ alone was low, all cases showed response; whereas when serum T³ alone was low, 6 cases showed no response. Thus, there was no positive correlation between TSH reactivity and serum concentrations of thyroid hormones.
3) No correlation was observed between TSH reactivity and the period after the onset of hyperthyroidism.
4) In 57 cases of Graves' disease, who were under treatment and in eumetabolic states, a comparison was made between TSH reactivity and the results of T³ suppression test. In T³ suppressed group, 19 showed response, and 3 showed no response; where as in T³ non-suppressed group, 18 showed response and 17 showed no response. In the group of T³ non-suppression as well as in the group of T³ non-suppression plus TRH no response, there was a significant elevation of serum T³ compared with the control group.
5) TRH test does not appear to be an appropriate test as a predictive method to know the permanent remission of Graves' disease.

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In regard to its biological and immunological characteristics, human chorionic somatomammotropin, otherwise known as human placental lactogen, can be found in its activity as a metabolism regulating hormone during pregnancy. This hCS is produced with a fairly rapid speed in the placenta and is secreted constantly with fairly great reserve. At the same time, its half life is so short that the serum hCS concentration sensitively changes according to the condition at the site of its production.
Therefore the clinical value of systematic measurement of hCS appears to be parameter of the function of placenta and indirectly, fetal growth and maturity.
On the other hand, estriol synthesis begins in the fetal adrenal with production of dehydroepiandrosterone (DHA), the major precursor of urinary estriol. Further metabolism includes 16-α hydroxylation which is performed largely in the fetal liver, and the formation of free estriol from 16-α OH-DHA which takes place in the placenta. So, it is considered that urinary estriol represents the function of feto-placental unit.
Therefore, to understand the clinical usefullness for monitoring the placental and feto-placental function, serum hCS and urinary estriol were measured with systematic serial estimation in comparison with the secretory behavior of these two hormones.
Furthermore, DHA-S dynamic test was performed to evaluate the feto-placental function.
HCS was measured by double antibodies radioimmunoassay and estriol was detected by the modified method of Brown's.
Summarized deta are as follow.
In the cases of normal pregnancy, serum hCS could be detected in the 8th week of gestation (0.02 μg/ml) and serum hCS concentrations showed a pattern of gradual increase reaching a plateau at about the 36th week of gestation (4-10 μg/ml).
Urinary estriol concentration at the 12th week of gestation was 0.5 mg/day and its secretion pattern also showed gradual increase according to the progress of the pregnancy.Urinary estiol level at the term was 10-30 mg/day.
In threatened abortion which terminated in the complete abortion, both estriol and hCS were low, or lowered even though they were in normal range at the beginning.
In the cases of intrauterine fetal death, both hormones were markedly low.
In the pregnancies with anencephalus, only estriol was low. On the contrary, hCS was low in a case of placental insufficiency.
In severe cases of sensitized rhesus incompatibility, estriol was abruptly lowered at the end of the pregnancy, but hCS was in normal range.
In the cases of SFD, hCS levels did not show any increasing pattern from the 28th week to term, but estriol levels were normal.
In the cases of severe toxamia of pregnancy, both hCS and estriol were lowered at the end of the pregnancy.
In the cases of pregnancy complicated with diabetes mellitus or prolonged pregnancy, both hormones were in the normal range.
To illustrate the correlation of these two hormones in the abnormal pregnancy, urinary estriol levels were plotted on the vertical axis and serum hCS was plotted on the horizontal axis. Low estriol zone and low hCS zone were determined and shadowed by drawing a line at the lowest levels of 95 % confidence limit of these hormones in the normal pregnancy. The area on which two shadowed area are superimposed was named as absolutely abnormal zone.
In threatened abortion which terminated in complete abortion, “the point” showing the two hormone levels was plotted in the absolutely abnormal zone from the onset of symptom or the point moved into there during the progress of clinical picture. In the cases of intrauterine fetal death, “the point” was in the absolutely abnormal zone. In the cases of anencephalus, “the point” was in the low estriol zone. In the cases of sensitized rhesus incompatibility,

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