Folia Endocrinologica Japonica

Separation of the Long-Acting Thyroid Stimulator and Thyrotropin in Serum by Rechromatography on DEAE-Sephadex A 25

Akito NOGUCHI, Seiya SATO, Hideo KURIHARA, Yuichi OZEKI

1964 Volume 40 Issue 1 Pages 5-8,1
Published: April 20, 1964
Released on J-STAGE: September 24, 2012

DOIhttps://doi.org/10.1507/endocrine1927.40.1_5

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An attempt was made to separate the LATS from human thyrotropin which was added to the hyperthyroid serum using the gel filtration on Sepadex G 200. The dextran gel “Sephadex G 200” was allowed to swell overnight in a buffer solution (0.01 M Tris-HCl in 0.02 M NaCl, pH 8. 6), and packed into a 2×40 cm. column. As shown in Fig. 1, four fractions were obtained. LATS was found in Fraction 2 (which contained 20-30% by weight of the original serum protein) and thyrotropin was found in Fraction 3. However, the separation of each thyroid stimulating substance in serum was not complete. A small amount of thyrotropin contaminated Fraction 2 because the TSH activity in Fraction 2 was reduced when neutralized by rabbit anti TSH (bovine) -serum. (Table 1.)
At the second step, rechromatography of Fraction 2 on Sephadex G 200 was performed using DEAE derivative of cross-linked dextran (DEAE-Sephadex A 25, 3.2 meq/ N/g). As shown in Fig. 2, LATS activity was observed in both the first and second fractions. However, thyrotropin was completely absorbed on DEAE-Sephadex (Table 2).
The weight of serum protein in the first and second fractions totaled 10.9% of the original protein.
No inhibition of LATS activity was observed after adding antiserum to the fractions obtained. From this result, it can be said that the LATS was almost completely separated by the two steps : Gel filtration on Sephadex G 200 and rechromatography of the second fraction on DEAE-Sephadex A 25.
Furthermore, it became clear that there are both LATS and thyrotropin in some hyperthyroid sera in which the 2-hour response is suppressed by the addition of the antiserum and the response curve changes to the prolonged type. This was also proved by the separation of LATS and thyrotropin in case 4.

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Diurnal Variation of Urinary Steroids and its Suppression by Corticosteroid Administration in Human Subjects

Koiti KAWAHARA

1964 Volume 40 Issue 1 Pages 9-33,2
Published: April 20, 1964
Released on J-STAGE: September 24, 2012

DOIhttps://doi.org/10.1507/endocrine1927.40.1_9

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Various kinds of investigations including the responce test to ACTH and the suppression test by corticosteroid are necessary to evaluate the adrenocortical function.
It is known that there is a diurnal variation of the adrenocortical secretion in human subjects. This diurnal variation is closely related to the regulation of the central nervous system.
The process of adrenocortical suppression by corticosteroid, the adrenocortical diurnal variation, and the influence of corticosteroid on this variation were studied. From these points of view, the author would like to emphasize the following 3 points :
(1) What is the difference of diurnal variations of urinary steroids between normal subjects and patients with endocrine disorders ?
(2) Are the diurnal variation patterns of urinary steroids reproducible ?
(3) How do corticosteroid administrations influence on diurnal variation patterns of urinary steroids ?
Diurnal variation of urinary steroids and its suppression by corticosteroid administration were observed in 6 normal subjects and 33 patients with endocrine disorders during a period of several days.
Urine samples were collected according to the following periods of a day. 1st period : 7A. M.12 N., 2nd period : 12 N.5P. M., 3rd period : 5P M.10 P.M., 4th period : 10 P.M.7 A.M.
The following results were obtained :
(1) In normal subjects, maximal values of both urinary 17-OHCS and 17-KS were seen in the 1st period or the 2nd period, minimal values being seen in the 4th period.
(2) In normal subjects, the pattern of diurnal variation of urinary 17-OHCS was reproducible every day but the reproducibility was not observed at all in cases of the patients.
(3) Dexamethasone was administered at 7 A.M. on the 2nd day in this experiments here described.
(4) The decreasing rate of urinary 17-OHCS and 17-KS due to corticosteroid administration was calculated, and the normal responce rate was more than 30%.
(5) In cases of pituitary disease, abnormal diurnal variations were observed frequently and the decreasing rate of urinary steroids was less than 30%.
(6) In cases of adrenocortical disease, normal diurnal variations were not observed at all. In cases of hypoadrenocorticism, urinary 17-OHCS increased after Dexamethasone administration. In one case of Cushing's Syndrome, urinary 17-OHCS levels during the sleeping time were relatively high but the decreasing rate of urinary 17-OHCS was normal.
(7) In cases of hyperthyroidism, there were no uniform patterns of diurnal variations and of decreasing rates of urinary steroids. In one case of hypothyroidism, a flat diurnal variation and a low decreasing rate were seen.
(8) In all cases of diabetes mellitus, the decreasing rate of urinary steroids was more than 30% and normal diurnal variations were observed in only 2 cases.
(9) In one case of anorexia nervosa, abnormal diurnal variations of urinary 17-OHCS and 17-KS were observed and the decreasing rate of urinary steroids was more than 30%.
(10) The frequency of occurrence of abnormal diurnal variations was 31.2% for 17-OHCS, 27.8% for 17-KS in normal subjects and 67.5% for 17-OHCS, 77.0% for 17-KS in the patients.

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Effects of Antithyroid Drugs on the Peripheral Metabolism of Thyroxine

Yoshiyuki SHIOKAWA

1964 Volume 40 Issue 1 Pages 34-48,4
Published: April 20, 1964
Released on J-STAGE: September 24, 2012

DOIhttps://doi.org/10.1507/endocrine1927.40.1_34

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The effect of propylthiouracil (PTU), methylthiouracil (MTU), mercaptoimidazole and potassium iodide was studied on the metabolism of thyroxine (T₄), and the following results were obtained :
1) Urinary excretion rate of I¹³¹ decreased and fecal radioactivity increased after I¹³¹-T₄ injection in thyroidection in thyroidectomized rats treated with PTU or MTU. No significant change was observed in the fecal and urinary radioactivity after I¹³¹-T₄ injection in thyroidectomized rats treated with mercaptoimidazole or potassium iodide.
2) The turnover rate of injected I¹³¹-T₄ decreased in thyroidectomized rats treated with PTU or MTU.
3) Distribution of I¹³¹ in the liver and intestines (with contents) increased after 6 hours of I¹³¹-T₄ injection in thyroidectomized rats treated with PTU.
4) The in vitro deiodination of I¹³¹-T₄ in rat liver homogenate was significantly decreased by PTU or MTU administered in vivo.
5) A decrease in weight gain and an increase in the plasma PBI and I¹³¹-triiodothyronine (I¹³¹-T₃) resin uptake was noted in T₄-maintained thyroidectomized rats after the administration of PTU or MTU for 2 months.
6) When PTU-treated rats were administered with varying doses of T4 in order to prevent goiter formation, doses of T₄ adequate to restore PBI to normal failed to prevent goiter completely, while goiter-preventing doses were associated with abormally high PBI values. Serum I¹³¹-T₄ resin uptake was well related with PBI.
7) The turnover rate of injected I¹³¹-T₄ decreased in euthyroid, hyperthyroid and hypothyroid patients by the administration of PTU or MTU.
8) Fecal excretion of I¹³¹ increased after I¹³¹-T₄ injection in euthyroid patients administered with PTU or MTU. Urinary I¹³¹ decreased in one patient administered with PTU.
9) An increase in the PBI was observed after the administration of PTU for 4 weeks in athyrotic patients treated with desiccated thyroid. No significant change was observed in serun I¹³¹-T₃ erythrocyte uptake in these patients.
These results indicate that PTU and MTU inhibit the peripheral metabolism of T₄ and that the inhibitory effect may be independent on the the alterations of thyroxine binding capacity of serum proteins since no effect was observed on serum I¹³¹-T₄ resin or erythrocyte uptake in these agents. It is suggested that the decrease in degradation of T₄ caused by PTU might influence the secretion of TSH.

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[title in Japanese]

1964 Volume 40 Issue 1 Pages 49-94
Published: April 20, 1964
Released on J-STAGE: September 24, 2012

DOIhttps://doi.org/10.1507/endocrine1927.40.1_49

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