In order to clarify the mechanism (s) which causes galactorrhea and amenorrhea in patients with Galactorrhea-Amenorrhea Syndrome (GAS) (Group A, n=20), composed of Chiari-Frommel Syndrome (CFS) (Subgroup I, n=3), Argonz-del Castillo Syndrome (ADCS) (Subgroup II, n=5) and Drug-induced Galactorrhea-Amenorrhea (DIG) (Subgroup III, n=12), we analysed basal plasma prolactin (PRL) and gonadotropin levels and their responsiveness to TRH and LH-RH, respectively in GAS patients. In addition, another group of galactorrheic patients without amenorrhea (Group B, n= 29) was selected, and further divided into three subgroups; subgroup I (n=7) with persisting postpartum lactation, subgroup II (n=7) of idiopathic galactorrhea, and subgroup III (n=15) induced by drug administration.
There were found unexpectedly high frequencies of normoprolactinemic patients (<23.7ng/ml) in 40% of GAS (66.7% in CFS, 40% in ADCS, and 33.3% in DIG). The PRL responsiveness to TRH, evaluated by %ΔPRL (peak PRL-basal PRL/basal PRL×100), tended to be high in ADCS and DIG (group after discontinuation of drugs) compared with those of normal subjects (n=12) and patients with primary hypothyroidism (n=21). PRL response was almost normal in CFS or DIG (group during drug administration).
Basal level of plasma gonadotropin in GAS was comparable to that of normal subjects. However, responsiveness of gonadotropin to LH-RH in GAS tended to be high compared with that of normal subjects.
The patients in group B (subgroup demonstrated almost parallel responses of PRL and gonadotropin, respectively, to those of corresponded subgroups in group A.
From the present results, we concluded that; 1) It seems likely that frequency of normoprolactinemic patients in GAS (Group A) is surprisingly high. 2) A still unclarified mechanism (s) for the occurrence of galactorrhea, not explained solely by plasma radioimmunoassayable PRL level and/or hyperresponsiveness of PRL to stimuli, may operate on a considerably large number of group A patients. 3) Decreased gonadotropin secretion at pituitary level seems not to be a main cause of menstrual abnormality in group A patients. 4) The same mechanism (s) as in group A patients may cause galactorrhea in group B patients.

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The secretory dynamics of plasma luteinizing hormone-releasing hormone (LHRH) and serum luteinizing hormone (LH) were studied in three hypogonadal women before and after chronic administration of mestranol.
Blood samples were obtained through an indwelling iv line every 15 min over 3 hours, and plasma levels of LHRH and LH were measured by radioimmunoassay. LHRH and LH pulses were defined as rising from nadir to peak that exceed 2 times the intraassay coefficient of variation.
All patients showed pulsatile LHRH and LH release before mestranol administration. The mean LH levels (89±20mIU/ml) and pulse amplitude (33±14mIU/ml) were significantly reduced after mestranol administration. On the other hand, the mean LHRH levels (1.87±0.49pg/ml) and pulse amplitude (0.92±0.41pg/ml) did not change significantly after mestranol administration. Pulse frequency (2-3 times/3 hrs) of LHRH and LH did not change after mestranol administration.
These data show that the chronic administration of estrogen to such patients cause a decrease in mean LH levels and amplitude of LH pulse without a decrease of pulsatile LHRH secretions. These results suggest that the chronic negative feedback action of estrogen on episodic LH release in women may be at the level of the pituitary gland and estrogen may change the pituitary sensitivity to LHRH.

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Serum concentrations of thyroid-stimulating hormone (TSH) were determined, using a highly sensitive immunoradiometric assay (IRMA), in 10 patients with Sheehan's syndrome.
Serum TSH levels in these patients were from 2.3 to 9.0μU/ml, with the mean of 6.4±2.3 (SD) μU/ml, and the data were similar to those measured by a conventional RIA method. The levels of serum TSH in these patients were normal or even higher than those of healthy women (1.8±1.3μU/ml).
After supplement therapy by cortisol, serum TSH levels decreased, but remained within the detectable range that was greater than 0.15μU/ml. After supplement therapy by l-thyroxine (T₄), serum TSH levels moderately decreased in all patients, and excessive l-T₄ administration resulted in a fall of serum TSH levels to lower than the detectable limit.
Thyroidal ¹²³I uptake was low in 3 out of 6 patients examined, which supports a recent hypothesis of reduced biological activity of the patient's TSH. While, the remaining 3 patients had normal thyroidal ¹²³I uptake, and administration of perchlorate had no effects on thyroidal radioactivity. Thus, it may be possible that in the former group of patients the TSH has a reduced biological activity, and in the latter group of patients, iodine trapping is intact but further synthesis and secretion of thyroid hormone from the gland are impaired.
When the response of serum TSH to TRH was examined, the peak serum TSH levels increased in all patients. The peak TSH levels were 4.8 to 10.2μU/ml with the mean of 7.5 μU/ml, but the data overlapped with those of normal subjects (peak level ranging 5.9-27.7 μU/ml). When the response was analyzed by a percent incitement from the basal level, the patients had only 93-250% increase after TRH, while normal subjects had 288-2339% increase, and there was no overlap between the two groups.
Our data indicate that the diagnosis of pituitary hypothyroidism cannot be established by determination of only basal level of serum TSH, but the analysis of percent increases of serum TSH in response to TRH gives us useful information for the diagnosis of this syndrome.

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Spontaneously hypertensive rat (SHR) にspironolactoneを投与し, 尿中prostaglandin E₂ (PGE₂)及びkininの排泄量について検討した。
SHR13匹を2群に分け, 1群(n=6)にはsesame oil 0.1mlを, その他の群(n=7)にはspironolactone 20mg/0.1ml of sesame oilを10日間皮下に投与し, 体重, 血圧, 尿量, 1日尿中Na, K, kinin, PGE₂排泄量を測定した。また実験終了日断頭にて採血し, plasma renin activity (PRA)を測定した。
その結果, spironolactone投与群には血圧の下降, 1日尿中Na排泄量の増加を認めた。一方, 1日尿中PGE₂の排泄量はspironolactone投与直後より著明に減少(p<0.05)し, 実験終了時迄低値のままであった。しかし1日尿中kinin排泄量はspironolactone投与群及び非投与群で同様な変化を示し, 両群間に有意差は認められなかった。
以上の成績より, spironolactoneには尿中PGE₂排泄抑制作用があり, この作用は腎のkinin産生を介したものではなく, spironolactoneの直接作用と考えられた。

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New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished.
Adopting of this new method for measuring plasma (P-) and urinary (U-) ATPI, and radioimmunoassay for P- and U-digitalis-like substance (DLS) - using crossreactivity to and digoxin antibody -, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure (CHF), primary and idiopathic hyperaldosteronism (HA), hyperthyroidism (BA) and chronic renal failure (CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control (C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis.
From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.

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Dependence of outset, maintenance of gravidity and onset of labor on different kinds of steroid hormones has long been the focus of debate with the underlying control mechanism of these hormones in question remaining left unestablished still in these days.
Of author's particular concern in this paper was the two-sided aspect of steroid functions. In fact, the steroid may stimulate mother's organ, fetus and placenta to produce much amount of steroid hormone throughout gravidic interval, while at the same time it may control the two contradictory processes, namely the maintenance of gravity and onset of labor through one and the same route. With a view to solve the complexity referred to above an effort has been made through a series of experiments particularity in the term of :
1. Dependent of a system capable to simultaneously determine concentrations of a variety of steroid hormones using the high performance liquid chromatography (HPLC);
2. Profile-analysis to be made on behavior of different kinds of steroids observable over gravidic interval under a support of HPLC system;
3. Behavior of different kinds of hemogenic hormones subsequent to an active DHAS loading in both group with- and without labor pains;
4. Influence of DHAS and gestation on activity of 11β hydroxy steroid dehydrogenase in placenta; Some of the results brought by these experiments, which are of some value to speculate on the mechanism of labor-onset and growth of fetus, may be summarized below in line with the preceding items :
1. The measuring system incorporating HPLC made it possible to determine 8 kinds of steroid hormones under systems of C19 and C21 readily in approx. 45 min., even when pretreatment is made involved in the procedure. It was also demonstrably verified that the system shows an acceptable sensitivity combined with a higher correlation with the RIA method.
2. Profile was successfully delineated of those steroids which would participate in controlling the labor pains inducing mechanism through a series of analytical works made on the behavior of steroid associated with the process of gravidism. With the approach of expected labor, it was seen that 5 kinds of steroid hormones comprising DHA, testosterone, pregnenolone, 20α OH-progesterone, and cortisol showed a marked increase. In contrast, androstenedione and progesterone begin to fall abruptly ever since several days proceeding the date of labor.
3. Gain of DHA, 17α OH-progesterone, due to DHAS-loading was clearly identified in the group with onset of labor pains. It was interesting to note that the group with labor pains showed a significant decrease of progesterone, while clearly in contrast the group without labor pains indicated a trend of its increase. These finding would play a purposive role in clearifing the significance of steroid in the occasion of parturition as a physiological process.
4. It is commonly agreed that cortisol play an important role to sustain fetus growth mechanism and safeguard of organism : and throughout the gravidic interval growth of fetus is kept controlled through a transformation of cortisol produced in much amount unplacenta into cortisone. By the way, the result from the present study revealed that DHAS produced by fetus would serve to suppress this transformation. These findings imply that a fetus can afford to control its growth selfsustaingly. In this context the foregoing findings would serve to explain the mechanism underlying the growth of fetus.
The forgoing results may be suggestive enough to clearfy the interaction of steroid hormones participating in the different processes such as maintenance of gravity, onset of labor and growth of fetus and further to offer general utility of the influence speculated on the theme of hormone-based mechanism of controlling gravidism.

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