The effects of ACTH preparations on the pituitary-adrenocortical function remain to be clarified in more respects than those of steroid drugs. In the present study, the author investigated the effect of synthetic ACTH-Z on the pituitary-adrenocortical function in a series of 76 patients under synthetic ACTH-Z therapy using the daily urinary excretion of 17-KGS as an index. The results are summarized as follows :
1) The administration of synthetic ACTH-Z in a dose of 0.25 mg or 0.5 mg q.d. was followed by a gradually declining tendency of the daily urinary excretion of 17-KGS. More particularly, after 1.5 months of synthetic ACTH-Z medication at either of these dosage levels, the response of urinary 17-KGS was found to have decreased to about 1/2 of its level at the beginning of medication.
2) The responsiveness of urinary 17-KGS was well maintained even after 3 months of intermittent doses of 0.25 mg of synthetic ACTH-Z (3 times a week, or every other day).
3) Synthetic ACTH-Z, when used in a smaller dose of 0.125 mg daily, produced a minimal stimulating effect on the adrenal cortex. When administered in a less frequent (twice weekly) dose of 0.25 mg, synthetic ACTH-Z failed to prevent or counterbalance atrophy of the adrenal cortex induced by small doses of steroid drugs (average total dose equivalent to 12.2 mg of prednisolone).
4) With the purpose of activating the steroid-atrophied adrenal cortex, synthetic ACTH-Z was administered in a daily or intermittent (every other day, or 3 times a week) dose of 0.25 mg. With the daily dosage regimen, the atrophied adrenal cortex temporarily exhibited a good response, but its responsiveness soon decreased again, and in the end, synthetic ACTH-Z administered in this mode failed to activate the adrenal cortex. With the intermittent dosage regimen, on the other hand, a tendency toward recovery of adrenocortical responsiveness was observed in half the cases studied. In the remaining half receiving steroids over a prolonged period of time, recovery of adrenocortical responsiveness was not attained to any appreciable extent.
These results might be interpreted as suggesting that the administration of synthetic ACTH-Z in an intermittent dose of 0.25 mg or 0.5 mg is advisable for the activation of the atrophied adrenal cortex. If this therapeutic regimen fails to initiate a tendency to recovery of adrenocortical responsiveness in a matter of a month or two, this implies that there is atrophy of the adrenal cortex severe enough to invalidate the therapeutic use of synthetic ACTH-Z.
5) The response of the adrenal cortex to 0.25 mg doses of synthetic ACTH-Z was distinctly suppressed by the concomitant use of steroids in 10 mg doses (as calculated on a prednisolone basis). Likewise, the response of the adrenal cortex to 0.5 mg doses of synthetic ACTH-Z was suppressed to 78%, 46% and 16%, respectively, by the conjoined use of steroids in doses of 20 mg, 30 mg and 40 mg or above.
6) The urinary 17-KGS level returned to the normal range in no more than 6 to 10 days after treatment with synthetic ACTH-Z given at 0.25 mg daily for 9 to 62 consecutive days.
From these findings it is inferable that recovery of the hypothalamo-pituitary-adrenocortical function following the discontinuation of synthetic ACTH-Z is far faster than that after the withdrawal of steroids.

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Studies were made on the effect of concomitant administration of dehydroepiandrosterone acetate (DHA-Ac) with progesterone on decidual growth in the rat.
Virgin female rats of Wistar strain weighing about 250 g were used. Daily vaginal smears were recorded and, during the time of vaginal cornification, the animals were made pseudopregnant by tapping the uterine cervix. Day 1 of the pseudopregnancy was designated as the day that the vaginal smears contained primarily leucocytes.
On day 4 of the pseudopregnancy, each animal was laparotomized midventrally, and bilateral ovariectomy and scratching of the uterine endometrium were performed. Progesterone, alone or in combination with DHA-Ac, was injected from day 4 of the pseudopregnancy (immediately after ovariectomy) through day 8.
On day 9 of the pseudopregnancy, all animals were killed. The weights of the uterus, and the deciduoma-inducing score, etc. were estimated.
Massive deciduomata weighing 2768±84 mg per uterus were induced in intact pseudopregnant rats. Treatment with 2 mg progesterone evoked maximal responses of only 754 ± 101 mg. The concomitant administration of 20 mg DHA-Ac with 2 mg progesterone reproduced the decidual weight observed in intact rats, but 2.5 mg or 5 mg DHA-Ac in combination with 2 mg progesterone was only slightly effective.
The weights of the uterus, the deciduoma-inducing score, the histological findings, and the effects of the DHA-Ac were discussed.

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1) Plasma renin activity (PRA) response to isometric exercise was studied before and after the intravenous administration of 0.2 mg/kg of propranolol in 8 normotensive and 10 normal renin hypertensive patients.
2) Handgrip exercise at the 30% level of maximal voluntary contraction (MVC) for four minutes induced a significant increase in PRA in either normotensive or normal renin hypertensive patients, while the increase in PRA in normal renin hypertensive patients was significantly higher than that in normotensive patients.
3) Pretreatment with the administration of propranolol inhibited an increase in PRA after handgrip exercise in either normotensive or normal renin hypertensive patients.
4) The results suggest that isometric handgrip exercise can induce an augmentation in renin release mainly by stimulation of the sympathetic nervous system in either normotensive or normal renin hypertensive patients. The possible mechanism of the exaggerated response in PRA to handgrip exercise in normal renin hypertensive patients has been discussed.

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Glycogen content, glycogen synthetase and glycogen phosphorylase were studied in the endometrial tissues of 28 women with normal menstrual cycles and in the decidual tissues of 24 women with normal early pregnancies.
The endometrial glycogen synthetase enzyme increased gradually from the proliferative phase to the secretory phase and reached maximal activity during the sixteenth to twenty-third days of the cycle, a time coincident with maximal glycogen content, while the glycogen phosphorylase reached its maximal activity on and after the twenty-fourth day of the cycle. In addition, glycogen phosphorylase activity in the decidual tissue during the early period of gestation (4-10 weeks) was lower than that in the endometrial tissue during the late secretory phase of the cycle, and in particular, the active form (-AMP) was significantly (p<0.005) low, with the result that the glycogen content in the decidua was significantly (p<0.05) higher than that in the endometrium.
On the other hand, in 20 normal pregnant women during the 6-10th weeks of gestation, the glycogen contents in the decidua and in the placental villi were 599 ± 44 mg/100 g wet weight (mean ± standard error of the mean) and 731 ± 55 mg/100 g, respectively, but the difference between them was statistically not significant. The levels of glycogen synthetase and glycogen phosphorylase enzyme in the decidua were significantly (p<0.005) higher than those in the placental villi.

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Isojima and co-workers have reported that crude hCG preparations, extracted from the urine of pregnant women and trophoblastic tumor patients, contained two immunoreactive components designated as Antigen 1 (Ag1) and Antigen 2 (Ag2). It was apparent that Ag1 was identical to highly purified hCG from immunological and biological studies. Ag2 possessed a portion of the antigenic determinants of Ag1 by the double diffusion test but no biological activity by the immature female rat ovarian augmentation method.
Recently Ag2 was found in commercial hCG preparations and separated by gel filtration on Sephadex G-100 in our laboratory. In this study, Ag2 has been characterized and compared to subunits of hCG by SDS disc gel electrophoresis and immunoelectrophoresis using antisera to hCG and hCGβ. Immunoelectrophoresis using absorbed anti-hCG antiserum resulted in the precipitin arcs of Ag2 and hCGα being displaced toward the cathode, but no precipitin arc of hCGβ was obtained. The precipitin lines with a single spur of Ag2 and hCGα showed that the antigenicity of Ag2 had a partial identity with that of hCGα. By immunoelectrophoresis using anti-hCGβ antiserum, the precipitin arc of hCGβ was migrated at the origin and also fused with that of Ag2 with a single spur. When subjected to SDS disc gel electrophoresis, Ag2 showed only a single migrating band and its molecular weight was estimated at approximately 30,000.
From these results, it has appeared that Ag2 was not similar to subunits of hCG, but possessed a portion of their antigenic components.

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Since Arimura et al (1975) reported the radioimmunoassay for somatostatin (GIF), the concentration of GIF in various organ and brain regions were determined by radioimmunoassay. Dubois et al (1975) reported that immunohistochemically somatostatin was located in the discrete cells of the pancreas as well as the hypothalamus, and from this result, they presented the concept of local hormone instead of systemic hormone which was up to that time accepted in endocrinology.
In this study, we developed the high specific anti-GIF serum using rabbits, and with the micro immunodiffusion method, we demonstrated that the precipitin band formed a circular fusion between the GIF and anti-GIF serum. This pattern of reaction was also seen in decidual immunodiffusion.
In addition, we developed the radioimmunoassay for GIF using this anti-serum and. measured immunoreactive GIF-like substances in villi and decidua of early pregnancy. The concentration of GIF-like substance with 2 N acetic acid extracted of villi and decidua were 0 to 30 pg/0.1 g dry weight.
At the same time, we demonstrated the presence of GIF-like substance-containing cells in the villi and decidua by indirect immunofluorescent method. The intensity of immunofluorescence was in cytotrophoblast rather than syncytiotrophoblast, and decidual stromal cell also reacted to the immunofluorescence.

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To investigate the effect of the therapeutic dosage (50-100 mg/day) of indomethacin (IDM), which is well-known to inhibit the synthesis of prostaglandins, on the human pituitary-gonadal axis, five experiments were performed.
Exp. I and Exp. II : Six healthy male subjects pretreated with IDM for two days (Exp. I), and 12 male patients receiving IDM for 1 to 19 months (Exp. II) were examined. In these two IDM treated groups, resting levels of plasma LH did not change, and LH response to LH-RH (100μg i.v.) slightly increased as compared with nontreated control males (N=11). Resting levels of plasma FSH, and FSH response to LH-RH statistically and significantly suppressed in both IDM treated groups, except for FSH response to LH-RH in the IDM pretreated healthy male group.
Exp. III : Two healthy women with regular menstrual cycles were treated with IDM for several days just before ovulation. These women's preovulatory LH surges were not blocked by IDM and were followed by a normal luteal pattern of basal body temperature.
Exp. IV : Ten female patients receiving IDM for 1 to 10 months were examined. In 9 patients, normal preovulatory LH surges were observed. It was interesting that the duration of the luteal phase was shortened (<10 days) in 5 of the 10 patients, and mid-luteal plasma progesterone levels were less than 500 ng/dl even if some of those patients had a normal duration of the luteal phase.
Exp. V : In five female patients treated with IDM for 1 to 9 months, mid-follicular gonadotropin secretions were estimated. Resting levels of plasma gonadotropins and their responses to LH-RH did not differ from the control female group (N=4).
From these results, it was indicated that (1) the therapeutic dosage of IDM acted on the central nervous system and the anterior pituitary, and then suppressed FSH secretion in male subjects. There was sexual difference in the IDM effect on FSH secretion, that is, mid-follicular FSH secretion was not affected by IDM in female subjects. (2) LH secretion was not suppressed by IDM in either male or female subjects in the mid-follicular phase. (3) The therapeutic dosage of IDM did not block the preovulatory LH surge and ovulation in female subjects, but IDM might act on corpus luteum and cause luteal dysfunction.

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As estetrol (E₄) is believed to be the steroid most likely to wholly dependent on fetal origin, we developed a radioimmunoassay for unconjugated and conjugated E₄ (E₄-U and E₄-G) and investigated plasma and urinary levels serially throughout the second half of pregnancy to establish their validity by means of monitoring or screening tests to assess fetal well-being.
E₄ exhibits a remarkable increase during the latter half of pregnancy. At term, the mean E₄-U level in maternal peripheral plasma was 0.67 ± 0.33 ng/ml, a five fold increase from that at 28 weeks; E₄-G was 4.57 ± 2.84 ng/ml, showing a four fold increase; and E₄-G levels in maternal urine were 1.68 ± 0.96 mg/day, showing a three fold increase from that at 28 weeks. E₄-U and E₄-G levels showed no diurnal change. The coefficient of the cor-relation between plasma E₄-U and E₄-G was 0.699, which is satisfactory, but no correlation was found between urinary and plasma E₄ levels. A significant correlation was shown between maternal and umbilical E₄-U (r=0.820) and E₄-G (r=0.608). No relationships between E₄ levels and birth weight were detected.
Preeclampsia, Rh-isoimmunization and diabetes mellitus are common complications of pregnancy which may cause latent fetal distress. Prenatal fetal assessment was performed by serial daily evaluations of these E₄ values. In pre-eclampsia resulting in a small full term baby, E₄ levels were mostly below normal mean values or failed to show an increased pattern. In addition, the E₄ levels decreased in one case of neonatal death. In Rh-isoimmunization, plasma E₄ -G levels were lower in the group affected severely by the hemolytic disease. In a patient with diabetes mellitus delivered of a healthy baby, E₄ levels were within the range of a normal pregnancy.
In order to evaluate fetal and placental reserve capacities as well as feto-placental function, the dehydroepiandrosterone sulfate (DHA-S) loading test was performed by loading selected subjects with 50 mg of DHA-S, then serially measuring the E₄ in the maternal plasma and urine. Intravenous infusion of 50 mg of DHA-S was completed in 60 minutes. A rapid and sharp increase of plasma E₄ was observed, reaching maximal concentrations at 120 minutes in normal pregnancies. However, urinary levels showed patterns similar to those reported for estriol (E₃). In some abnormal pregnancies, no increased or delayed patterns were observed in plasma E₄ -G levels, while the serial levels remained within the normal range. This possibly suggests that in these pregnancies, fetal functions had been inhibited or had reached their limit.
It is concluded that the simultaneous determinations of serial E₄ levels accompanied by the DHA-S loading test may be of value in assessing fetal well-being and reserve capacity and may therefore improve fetal and neonatal prognosis in abnormal pregnancies.

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