We have studied a 13-yr-old male student who had low TBG but showed a normal localization of thyroxine binding in the prealbumin and normal protein fractions. Neither physical abnomality was present, except a slight struma, nor noted prior illness was experienced. No decrease of the thyroxine binding by serum TBG was found in his family pedigree.
The subject had a low protein bound iodine (PBI), a high T₃-I¹³¹ resin uptake, a normal or subnormal serum free thyroxine, a normal basal metabolic rate (BMR), a normal serum chloesterol and I¹³¹-thyroidal uptake. Other laboratory findings indicated that urinalysis and liver function were normal, and that urinary 17-KS, 17-OHCS and catecholamine excretion were also within normal limits. And the iron-binding capacity was normal.
The half-life of thyroxine-I¹³¹ was markedly shortened. A low PBI or reduced extrathyroidal thyroxine (ETT) was probably balanced by a compensatory increase in the fractional rate of turnover of thyroxine which resulted in a normal hormonal disposal. After TSH injection, PBI varied from 3.0 to 3.4 microgr/100m1, I¹³¹-thyroidal uptake from 20 to 35%. Administration of estrogen or anabolic steroid gave no significant difference in PBI and total TBG.
These findings suggest that the present case is not hereditary but individual, apparently healthy and eumetabolic.

View full abstract

There are two kinds of gonadotropin excreted in the urine, viz., pituitary gonadotropin and chorionic gonadotropin, both of which are proteohormones. The present study was designed to investigate the electrophoretic characteristics of the two proteohormones by separating the two compounds by means of paper electrophoresis, and determining the position of the gonadotropically active component on the electrophoretic pattern by bioassay. The gonadotropin materials used in this study were as follows : Hypohorin, a freezedried anterior pituitary preparation, powdered desiccated anterior pituitary preparation, and HCG powder, a placental preparation extracted from placenta taken during the early stage of pregnancy and also from the latter stage of pregnancy. Gonadotropin in the urine was extracted by the carbowax concentration method as previously reported.
Kobayashi's method of paper electrophoresis was employed in this study. Simultaneously and parallel to the gonadotropin preparation, human blood plasma of known electrophoretic characteristics was also run in order to determine the relative mobilities (R-Alb) of each fraction of gonadotropin in relation to albumin of blood plasma. The gonadotropic activity of each fraction was determined by the uterine weight method using young mice.
Pituitary gonadotropin exhibited 5 staining zones and the gonadotropic active fraction was detected in the R-Alb VI and VII fractions, i.e., in the zone corresponding to the a, aspect of β-globulin fraction of human blood serum. Chorionic and placental gonadotropin also exhibited 5 staining zones. The gonadotropin active fraction was detected in the R-Alb V and VI fractions, i.e., in the zone corresponding to β-golbulin and γ-globulin fractions of human blood serum.
Samples taken from the urine of pregnant women both during the first and third trimesters exhibited 4 staining zones, and gonadotropin active zone was detected in the R-Alb VI fraction, i.e., in the region corresponding to β-globulin of human blood serum. Samples taken from the urine of climacteric women by the carbowax method alone did not exhibit any staining zone; however, when the ammonia alcohol precipitation method was also used, a gonadotropin active zone was detected in the region corresponding to the β-and γ-globulin fractions of human blood serum.
From the aforementioned data, it is evident that the electrophoretic of pituitary gonadotropin and chorionic gonadotropin differ with each other, i.e., they have different mobilities. The active zone of the pituitary ganodotropin lies mostly in the region corresponding to α-globulin fraction of human blood serum, and the placental gonadotropin in the region corresponding to β-and γ-globulin fractions of human blood serum. It is assumed that the gonadotropin excreted in the urine has an active core with conjugated protein.

View full abstract

The function of the adrenal medulla and of the pituitary-adrenocortical axis has been studied in both asymptonic and symptomatic patients with bronchial asthma.
Markedly increased excretion of adrenalin adn nor-adrenalin are induced by the attack of asthma, while in asymptomatic state noradrenaline alone increased.
In the asymptomatic, baseline excretion of urinary 17-OHCS is normal. Admini-stration of SU-4885 and ACTH-Z shows normal response. Elevation of plasma cortisol after administration of bacterial pyrogen is within normal limits. Moreover, diurnal rhythm of plasma cortisol shows normal pattern. So that the function of pituitary-adrenal axis in these patients are normally maintained.
In the symptomatic, however, baseline of urinary 17-OHCS is lower than that of controls. After administration of 100mg. of cortisol, urinary excretion of 17-OHCS also decreases as compared with the normal. On the other hand, plasma cortisol level is markedly elevated. Although GFR and RPF decreases during an attack of athma, halflife of cortisol in blood is within normal limts, so that removal rates of cortisol is without change. Moreover, it is shown that cortisol secretion rates increase significantly. Thus, the elevation of plasma cortisol is due to a transient hypersecretion from the adrenal in response to the attack of asthma and not due to a retention in plasma. These results demonstrate that the function of the pituitary-adrenal axis in the symptomatic is also normally maintained, and it is suggested that both a temporary impaired reanl function and an altered cortisol metabolism, could well cause a decrease of 17-OHCS excretion despite the elevation of plasma cortisol level.
Although a number of studies were performed in an attempt to elucicdate pituitary-adrenal function in patients with bronchial asthma, conclusions have been contradictory.
The majority of reports confirmed that the urinary excretion of 17-KS and 17-OHCS were low in asthmatic patients when compared with that of the normal, indicating pituitary-adrenal hypofunction. Others demonstrated, however, that excretion of 17-KS and 17-KGS in these patients are within normal limits. On the other hand, Siegel and his associates found that plasms 17-OHCS concentration was high during attacks of asthma, suggestiong normal, or hyperfunction of pituitary-adrenal axis.
These conflicting findings stimulated us to make further extensive studies of pituitary-adrenal activity, along with the function of the adrenal medulla, in asthmatic patients.

View full abstract

Plasma TSH levels in rats exposed to cold were investigated and the following findings were obtained.
Plasma TSH levels elevated soon after exposure to a moderate cold of 8°C and reached the peak 30 minutes after exposure. The elevated level of plasma TSH was sustained for only 2 hours. Thereafter, it decreased rapidly toward pre-exposure levels. A relatively low level, but significantly higher than control value, was observed to be maintained in rats kept at 8°C for 4 weeks.
During the initial stages of cold exposure at 8°C pituitary content of TSH decreased markedly from control value of 803 mU per gland to 624 mU after 6 hours and 303 mU after 24 hours. Percentages of the decrease were 22.3 and 62.3 per cent, respectively, indicating an initial burst of the stored TSH in the adenohypophysis.
Exposure of rats to a mild cold of 15°C resulted also in a marked increase in the plasma TSH level after 30 minutes and 2 hours. Thereafter it decreased to the level of preexposure, with an exception of value at 16 hours after exposure. Prolonged exposure at 15°C for 4 weeks showed no more increase in the plasma TSH content. A similar but a little prolonged elevation of the plasma TSH was observed in rats exposed to a severe cold of 0°C.
These results indicate that a bulk of TSH is released from the adenohypophysis in the early phase of cold exposure irrespective of its intensity.

View full abstract

Details of a procedure for estimating cortisol secretion rate (CSR) were presented and the validity of this method was investigated. Using this method, CSR in normal subjects, in subjects under stress and in patients with adrenocortical dysfunctions were estimated.
1) After an intravenous administration of a treacer dose of cortisol-1, 2-³H, 24-hr. urine was collected. Two major urinary metabolites of cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE), were purified paper-chromatographically and their specific activities were determined by liquid scintillation counting and Porter-Silber method. The estimated value of CSR was calculated by dividing total administered radioactivity by the specific activity of THF or THE.
For purifying both THF and THE, ethylene dichloride-formamide system was used as the first paper chromatography. In the next step, Bush B₅ system was used for purifying THF, and E2B system or Bush B₅ system for purifying THE.
2) When E2B system was used as the second paper chromatography for purifying THE, two values of CSR, wihch were independently calculated from the specific activity of THF and from that of THE, did not agree with each other.
In order to find which value reflects more actual cortisol secretion rate, known amounts of cortisol were given to the patients with hypoadrenocorticism, and apparent CSR were estimated. The estimated values agreed with the doses administered when calculation was made from the specific activity of THF, while they showed much smaller values with calculation from that of THE. This fact suggested that cortisol metabolite or metabolites, not Porter-Silber chromogenic, contaminated THE. When Bush B₅ system was substituted for E2B system as the second paper chromatography for purifying THE, the values of CSR calculated from the specific activity of THE approached the values from THF.
3) The value of CSR calculated from the specific activity of THF was 14.6±3.3 (S.D.) mg/day in 10 resting normal subjects, and was 13.7±3.2 mg/day in 10 lightly working normal subjects. There was no significant difference between the two groups. A slightly higher value, 17.8±5.0 mg/day, was obtained from 8 heavy muscle laborers.
4) The value of CSR in 10 resting and 10 lightly working normal subjects, 14.1±3.2 mg/day, agreed with the smallest normal value that was previously presented by foreign investigators. This may be due to the smaller body size of Japanese people than that of foreign people.
At the same time, CSR in subjects under stress and in patients with adrenocortical hyper-and hypofunctions were studied. From these data, it was finally justified to adopt 7.8-20.5 mg/day as the normal range.
In addition, CSR per kg of body weight and per m² of body surface area were also evaluated. The adopted normal ranges were 145-358 μg/kg/day and 5.3-12.6 mg/m²/day.

View full abstract

A new method using T.L.C. and double isotope derivative dilution assay for the determination of a small amount of aldosterone in various biological materials is reported. This method will be strongly recommended for its speediness, convenience and economy.
I wish to thank to Dr. Tatsuo Oda, Akio Ishii and Hideo Suzuki for the valuable suggestions and advices, and to Prof. Dr. Kenzo Oshima for his continuous encouragrement in this study.

View full abstract