Epidemiologic study on dwarfism (height under “Mean-2.58 S.D”) was performed in elementary schools and junior high schools in Niigata Prefecture. Results were as follows :
1) Prevalences of dwarfism were 0.17% in elementary schools (age at 6-12 y.o.), 0.26% in junior high schools (12-15 y.o.), and 0.20% in all (690 dwarf students of 339,854 students). Prevalences in female was 1.3 times as high as that in male.
2) 476 of 690 dwarf students were further examined. 50 (10.5%) of them had pituitary dwarfism and 2 (0.4%) had hypothyroidism. 24 of 50 cases with pituitary dwarfism and one of 2 cases with hypothyroidism were newly diagnosed in this study.
3) One family who seemed to have autosomal-dominant inherited pituitary dwarfism was found in this study. The heights of brothers (11 y and 9 y 6 m) and their mother were under “Mean-4.0 S.D” and they were diagnosed as patients with isolated GH deficiency. The heights of their grandmother and aunt were also under “Mean-4.0 S.D”, but they have not been examined. In both brothers and their mother, plasma GH levels didn't respond to iv bolus injection of GRF (1.0μg/kg), and brain CT showed empty sella.
4) Of 476 dwarf students, 249 (52.3%) had constitutional dwarfism, 118 (24.8%) had either constitutional dwarfism or delayed adolescence, 23 (4.8%) had Turner's syndrome (including Noonan's syndrome), and 13 (2.7%) had chondrodysplasia.
5) Dwarf female whose ratios of the maximum response of plasma LH to LHRH/ the maximum response of plasma FSH to LHRH were more than 2.0 and dwarf male whose plasma basal level of testosterone were more than 40 ng/ml were expected to become adolescent in the near future,
6) Plasma IGF-I levels determined by RIA with unextracted samples did not clearly differenciate pituitary dwarfism from others.

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16α-hydroxyandrost-4-ene-3, 17-dione (16αOH-A) was measured in pregnant women by radioimmunoassay (RIA) with specific antiserum. After extraction of the serum the 16αOH-A fraction was separated by the use of Sephadex LH-20 mini column.
Lately, high performance liquid chromatograph (HPLC) was combined with RIA (HPLC-RIA) for the measurement of various kinds of steroids from an extract of a serum or urine sample.
The purpose of this study was to establish the HPLC-RIA method for the measurement of 16αOH-A in pregnant women.
Pooled serum was extracted twice with 5 volumes of ethylether, and the combined extract was separated either by LH-20 mini column with the solvent system n-hexane : benzene : methanol = 8 : 1 : 1 or by HPLC ODS column with MeOH : CH₃CN : H₂O = 60 : 10 : 30. The 16αOH-A fraction was collected and an aliquod was measured by RIA.
The coefficients of variance for intra and inter-assay (n=10) were computed to be 8.6 and 12.1% with LH-20, and 7.2 and 11.7% with HPLC, respectively. Recovery rate was 95.7± 7.4% with LH-20 and 92.5 ± 8.7% with HPLC.
The values of 16αOH-A as measured following two kinds of chromatographies were closely related to each other. The mean serum hormone concentrations±standard errors were as follows. In maternal peripheral blood up to 11 weeks 1.04 ± 0.19 (LH-20) and 0.55 ± 0.10 (HPLC), 12 to 23 weeks 1.22 ± 0.23 (LH-20) and 0.67 ± 0.77 (HPLC), 24 to 36 weeks 2.24 ± 0.42 (LH-20) and 2.27 ± 0.28 (HPLC), above 37 weeks 1.64 ± 0.52 (LH-20) and 1.85± 0.34 (HPLC), second stage of labor 5.07± 1.28 (LH-20) and 4.73 ± 0.54 (HPLC) ng/ml of steroid, respectively, were measured. Steroid concentration in umbilical arterial and venous blood were 7.87 ± 1.41 (LH-20), 3.75 ± 0.83 (HPLC) and 8.69± 1.66 (LH-20), 5.38±0.87 (HPLC) ng/ml, respectively.
The values of 16αOH-A levels tended to increase as gestation proceeded. These data suggest production of 16αOH-A by the feto-placental unit. An elevated level of 16αOH-A is found in the umbilical venous blood as compared to the arterial samples. This indicates an extensive conversion. After onset of labor, the 16αOH-A levels were significantly increased because of precursor steroid 16α-hydroxydehydroepiandrosterone-sulfate is mobilized by the stress of labor.
This study shows that the HPLC-RIA method is applicable to the measurement of related steroids produced in the feto-placental unit from a small amount of samples.

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Inactive renin in the brain of spontaneously hypertensive rat was investigated. The results are as follows.
1) Treatment with either trypsin or glandular kallikrein of the brain tissue extract caused a rapid and apparent increase in the renin activity at either 0 or 27°C.
2) The molecular weight of the active renin was estimated to be 41,000 or 50,000 daltons, while that of the trypsin-activatable inactive renin was found to be 44,000 or 57,000 daltons on a column chromatography with Sephadex G-100.
3) The contents of the active renin was the highest in the hypothalamus, followed by the striatum, thalamus, midbrain, medulla oblongata, cerebral cortex and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by the striatum, thalamus, cerebellum, midbrain, cerebral cortex and medulla oblongata.
4) These results suggest that inactive renin (s) exist in the brain of spontaneously hypertensive rat. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin (s), which, in turn, plays at least in part a role in the blood pressure regulation through generation of angiotensin II in spontaneously hypertensive rats.

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The effect of bradykinin (BK) on the release of β-endorphin-like immunoreactivity (β-END-LI) in rats was studied in in vivo and in vitro. Intraperitoneal injection of BK at 5 μg/ 100 g body weight resulted in a significant increase in the plasma β-END-LI level after 15 min. BK at concentrations of 10^-12 - 10^-7M also caused dose-dependent stimulation of β-END-LI release from the dispersed cells of the anterior pituitary of rats. On gel chromatography, the β-END-LI released by incubation of the cells with 10^-7M BK separated into two components; one eluted in the same positions as human β-lipotropin and the other as human β-endorphin. BK did not stimulate β-END-LI release in Ca⁺⁺-free medium. Addition of 10^-3M verapamil, 10^-6M dexamethason or 10^-7M somatostatin to the incubation medium inhibited BK-induced β-END-LI release from the cells. Ouabain (10^-5M) also stimulated β- END-LI release, but its effect was not additive with that of BK. These results indicate that BK stimulates β-END-LI release and that calcium ion is involved in the mechanism of this effect.

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The present study was designed to clarify the role of serum angiotensin I-converting enzyme (ACE) in the occurrence and maintenance of hypertension in essential hypertension (EH). For this purpose, following experiments were carried out : 1) Correlations between serum ACE activity and renin activity (PRA), aldosterone concentration (PAC) and bradykinin concentration (PBC) in plasma, and blood pressure (BP) as well as serum creatinine levels. 2) Circadian rhythm of serum ACE activity, and 3) Effect of furosemide, upright posture, both furosemide and upright posture, propranolol, indomethacin, 9α-fluorocortisol or angiotensin II (A-II) on the serum ACE activity, PRA, PAC and circulating plasma volume (CPV).
The following results were obtained :
1) The serum ACE activity was 30.2 ±5.0 U/ml (means ±SD) in EH as a group, which was significantly higher than that (27.3 ± 3.9 U/ml) in age matched normotensive subjects (NT) (p<0.001). While there was no significant difference in the enzyme activity between low-renin EH (LREH) and NT, a significant difference was found between normal- (NREH) or high-renin EH (NREH) and NT (p<0.05 for NREH, p<0.01 for HREH).
2) A negative correlation was observed between enzyme activity and age in EH (r=-0.221, 0.05<p<0.10) as well as in NT (r=-0.306, p<0.05).
3) No significant relationships were observed between enzyme activity and BP in either EH or NT.
4) There was a significant positive correlation between enzyme activity and PRA in NT (r=0.501, p<0.001), NREH (r=0.658, p<0.001) and HREH (r=0.695, p<0.001). However, no significant relationship was found between them in LREH. The enzyme activity was significantly correlated to PAC in NT (r=0.368, p<0.01), NREH (r=0.567, p<0.001) and HREH (r= 0.529, p<0.01), but not in LREH. Although no significant correlation was observed between enzyme activity and PBC in NT, NREH and HREH, a significant relationship was found in LREH (r=-0.460, 0.05<p<0.10).
5) The enzyme activity was not related to serum creatinine levels in EH as well as in NT.
6) In NT, the serum levels of ACE activity reached a maximum values at 6 : 00 a.m. or 9 : 00 a.m., and gradually decreased between 6 : 00 p.m. and 3 : 00 a.m. An almsot similar circadian rhythm of enzyme activity was found in EH. The rhythm was parallel that of PRA and PAC in NT, NREH and HREH, but not in LREH.
7) The serum ACE activity was significantly increased by treatments with furosemide, upright posture and both furosemide and upright posture in NREH and HREH as well as NT, parallel with changes in PRA in response to these types of stimulations. On the other hand, serum ACE activity was lowered by treatments with propranolol, indomethacin, 9α-fluorocortisol or A-II, also in parallel with changes in PRA. However, in LREH, serum ACE activity was not changed with upright posture and propranolol, but it was changed with furosemide, 9α-fluorocortisol or indomethacin in parallel with change of CPV.
In conclusion, the ACE may be secreted into circulation from the kidney in response to renin release and be activated the renin-angiotensin-aldosterone (R-A-A) axis in NREH and HREH as well as in NT. On the other hand, in LREH, serum ACE may be inactivated the kallikrein-kinin system rather than that the R-A-A axis and be modulated BP and water-electrolyte balance.

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