Thyrotropin-releasing hormone loading was performed on 91 patients with asymptomatic autoimmune thyroiditis. Four women had no response to this loading test and had high levels in serum total and free thyroxine (TT4, FT4) and in serum total and free triiodothyronine (TT3, FT3). These patients might be classified as subclinical hyperthyroidism (Group G). Twenty-four patients had normal levels of both basal and peak thyrotropin after loading and were classified as Group I. There were no significant differences between 45 controls (Group C) and Group I patients in serum thyroid hormone levels. Patients with normal basal and high peak levels of thyrotropin were included in Group II. The number of patients in this group was 53. The mean levels of basal and peak thyrotropin were 4.8μU/ml and 39.6 μU/ml, respectively, and were significantly higher than in Group C and Group I (PC0.005). In 10 patients classified as Group III with high levels of both basal and peak thyrotropin, serum concentrations of TT4, FT4 and FT3 were significantly lower than in the other groups (PC0.025); however, significant differences in TT3 could not be seen among them. Serum cholesterol levels gradually increased from Group C to Group III. There were significant differences between Group C and Group II (P<0.05).

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The effects of canrenone K (Soldactone) on 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase and 18-hydroxylase activities were determined in vitro using isolated mitochondrial and microsomal fractions of the bovine adrenal glands. There was dose-related inhibition of 3β-hydroxysteroid dehydrogenation in the concentration between 10^-8M and 10^-3M, and 11β-hydroxylation and 18-hydroxylation in the concentration between 10^-7M and 10^-3M, respectively. The concentration of 50% inhibition of 3β-hydroxysteroid dehydrogenase activity was 8.5×10^-7M and those of 11β-hydroxylase and 18-hydroxylase activities were 5×10^-5M and 6×10^-6M, respectively. NADPH added to a mitochondrial fraction or NAD to a microsomal fraction had no effect on the inhibition of conversion in the presence of canrenone K. The results indicate that canrenone K inhibited 3β-hydroxysteroid dehydrogenase in the pharmacological dose, 11β-hydroxylase and 18-hydroxylase in a higher concentration, and with the exception of NADPH or NAD, it may inhibit the generating system directly.

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The effect of histamine on the release of β-endorphin-like immunoreactivity (β-END LI) in rats was studied in vivo and in vivo experiments. Intravenous injection of 100μg/ 100g BW of histamine resulted in a significant increase in the plasma β-END-LI level 5, 15 minutes after the injection. Histamine at concentrations of 10^-12 to 10^-9M also caused dose-dependent stimulation of release of 0-END-LI from the dispersed cells of the anterior pituitary of rats. On gel-chromatography, the β-END-LI released by incubating the cells with 10^-9M histamine consisted of two components, which eluted in the same positions as human β-lipotropin and human endorphin, respectively.
Addition of 2mM CoCl₂ to the incubation medium inhibited histamine-induced β-END LI release from the cells. Histamine H₁ receptor antagonist (10^-6M) inhibited histamine-induced β-END-LI release from the cells. Histamine H₂ receptor antagonist (10^-6M), however, did not inhibit histamine-induced β-END-LI release. These results indicate that histamine acts directly on the anterior pituitary cells to stimulate β-END-LI release and that calcium ion is involved in the mechanism of this effect.

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Serum total thyroxine (t-T₄), free thyroxine (f-T₄), total triiodothyronine (t-T₃), free triiodothyronine (f-T₃), reverse triiodothyronine (r-T₃) and thyroxine-binding globulin (TBG) levels were measured by radioimmunoassay in pregnants, infants, children and adolescents.
The mean t-T₄ and TBG concentrations in cord blood (9.0±0.3μg/dl, 24.4 1.1 μg/ ml, mean±SE) were significantly lower than the levels in maternal blood (12.1±0.6 μg/di, 40.3±2.3 μg/ml), whereas mean f-T₄ concentrations in cord blood (1.13±0.04 μg/dl) were significantly higher than the values in maternal blood (0.86±0.03 μg/ml). The mean t-T₃ and f-T₃ concentrations in cord blood (48±2 ng/dl, 1.1±0.1 pg/ml) were much lower than the levels in maternal blood (136±5 ng/dl, 2.6±0.1 pg/ml). The r-T₃ concentrations in cord blood (192±4 ng/dl) were markedly higher than the maternal levels (46.6±3.7 ng/dl). These results suggest that in the fetus the conversion of T₄ to r-T₃ was greater than that of T₄ to T₃ due to a greater ratio of activity of 5-monodeiodinase to that of 5'-monodeiodinase.
In relation to the changes in thyroid function after birth, t-T₄ and f-T₄ values showed parallel changes while t-T₃ and f-T₃ levels increased rapidly during the first month and t-T₃ levels remained unchanged between 1 and 11 months, whereas f-T₃ levels and f-T₃ /t-T₃ ratio increased gradually during the same time. T-T₃ levels in children 1 to 15 years of age were slightly lower than the levels in infants 1 to 11 months. R-T₃ values decreased progressively from 5 days to 1-3 months and continued to decline until 4 years of age. Values between 4 and 15 years were not changed. T-T₃/t-T₄ ratio increased markedly 1-3 months after birth. This indicates that the activity of 5'-monodeiodinase was elevated rapidly after birth and suggests that the rapid increase of T₃ levels after birth was due to enhanced enzymatic activity as well as higher TSH levels. R-T₃ /t-T₄ ratio decreased rapidly after birth and continued to decrease during years 1-3. This indicates that the change of activity of 5-monodeiodinase was different from that of 5'-monodeiodinase.
In the prepubertal and pubertal boys and girls, f-T₃ levels in early pubertal (Tanner stage II) boys were slightly higher, and t-T₃ levels in pubertal (Tanner stage IV) boys were lower than the values in other stages while there were no significant changes in girls. These results suggest that these changes were due to the changes of TBG concentration and/or of conversion of T₄ to T₃.

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Recently, the role of the serotonergic nervous system has been implicated in blood pressure regulation and in the pathogenesis of hypertension. However, the effects of 5-hydroxytryptamine (5-HT) administration on hemodynamics have been notoriously inconsistent and the precise mechanism of the blood pressure regulation of the serotonergic nervous system has not been elucidated yet. In our previous study, we demonstrated that the intracerebroventricular (i.c.v.) administration of 5-HT in rats elicited consistent pressor response with concomitant increase in plasma norepinephrine and that the pressor response was abolished by systemic pretreatment of phenoxybenzamine or by serotonin receptor antagonist, methysergide. The purpose of this experiment is to investigate further the relationship between the sympathetic nervous system and the serotonergic nervous system.
MATERIALS AND METHODS : Male Wistar rats weighing approximately 200g were used. A cannula was inserted stereotaxically into the anterior horn of the lateral cerebral ventricle. According to the experimental protocol, the rats were divided into 3 groups. One group of rats received 6-hydroxydopamine (6-OHDA) from the tail vein at the dose of 200mg/kg each on 10, 2 and 1 day before the experiment (6-OHDA i.v. group, n = 16). The rats of the control group received saline alone (6-OHDA i.v. control group, n= 19). Another group of rats received i.c.v. 6-OHDA at the dose of 200 pg each on 2 and 1 day before the experiment (6-OHDA i.c.v. group, n = 6) and the control rats received saline alone (6-OHDA i.c.v. control group, n = 8). The remaining group of rats were subjected to bilateral adrenalectomy under ether anesthesia 24 hours before the experiment (Adx group, n= 8) and the control rats were subjected to sham adrenalectomy (Sham adx group, n= 6). In all rats, a cannula was inserted into the carotid artery on the day before the experiment. The experiment was performed under conscious state with the exception of those received i.c.v. 6-OHDA that showed extreme restlessness. After the resting observation of at least 20 minutes, 5 μg of 5-HT were given i.c.v. and mean arterial pressure (MAP) as well as heart rate (HR) were observed for about 20 minutes.
RESULTS : Resting MAP and HR of the 6-OHDA i.v. group did not differ significantly from those of the 6-OHDA i.v. control group (101.8±1.7 mmHg, 428.7±15.7 bpm and 102.8±2.3 mmHg, 414.4±10.4 bpm, respectively). Whereas i.c.v. 5-HT elicited significant pressor response and decrease in HR at 2 minutes after the administration in the 6-OHDA i.v. control group (+29.9±2.6 mmHg and -46.0±8.2 bpm, respectively), both pressor response and decrease in HR were significantly suppressed in the 6-OHDA i.v. group (+15.6±4.2 mmHg and -5.0±6.4 bpm, respectively). There were no significant difference in resting MAP and HR between the 6-OHDA i.c.v. control group and the 6-OHDA i.c.v. group. I.c.v. 5-HT administration elicited significant pressor response (+28.6±3.7 mmHg) and decrease in HR (-44.3±8.7 bpm) in the 6-OHDA i.c.v. control group, however, there were no significant changes in MAP and HR in the 6-OHDA i.c.v. group (+3.3±1.6 mmHg and -20.0±16.5 bpm, respectively). In the Adx group, resting MAP and HR did not differ significantly from those of the Sham adx group (98.1±3.7 mmHg, 455.0±20.7 bpm, 102.5±4.7 mmHg and 403.3±13.0 bpm, respectively). Pressor response and decrease in HR at 2 minutes after the i.c.v. 5-HT were significant and similar in those two groups (+25.0±3.4 mmHg, -40.4±17.4 bpm in the Adx group and +23.3±2.7 mmHg, -43.3±12.2 bpm in the Sham adx group). DISCUSSION AND CONCLUSIONS : Since i.c.v. administration of 5-HT elicited pressor response and the change was significantly suppressed either by i.v. or by i.c.v. pretreatment with 6-OHDA,

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There is considerable information suggesting that dopamine is a physiological regulator of aldosterone secretion. Metoclopramide, a specific dopamine antagonist, elicits a rapid rise in plasma aldosterone independent of the known aldosterone-regulating factors. However, the mechanism and the site of action of metoclopramide, whether adrenal or extraadrenal, in stimulation of aldosterone production remain to be defined. The present studies were designed to investigate the mechanism of dopaminergic control of corticosteroid secretion and to determine at which step in the aldosterone biosynthetic pathway metoclopramide and dopamine exert their effect.
Plasma concentrations of progesterone, 11-deoxycorticosterone (DOC), and cortisol were not altered by a bolous intravenous administration of 10 mg metoclopramide in 8 healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.9±2.8 (Mean±2SD) ng/100 ml to a maximum level of 18.2±4.7 ng/100 ml, 18-hydroxycorticosterone 0.09μg/100 ml to a maximum of 0.85±0.22 μg/100 ml. The aldosterone, 18-OHB and corticosterone responses displayed a parallel time course, with a significant response of each occurring within 5 minutes after metoclopramide administration. These data suggest that metoclopramide may modulate the activities of 18-hydroxylase and 1113-hydroxylase.
Studies in vitro revealed that metoclopramide (10^-8-10^-4M) had little effect on basal production of aldosterone, 18-OHB and corticosterone from human adrenal slices. Dopamine (10^-4M) did not alter the basal secretion of aldosterone, 18-OHB and corticosterone, but suppressed the secretion of these 3 mineralocorticoids by ACTH, which were diminished by addition of 10^-4 M metoclopramide.
There was a concentration-dependent inhibitory effect of dopamine on conversion of corticosterone to 18-OHB and DOC to corticosterone in vitro using bovine adrenal mitochondrial fractions. IC₅₀ of dopamine inhibiting 18-hydroxylation and 11β-hydroxylation were 7.5×10_-7M and 9.5×10_-4M, respectively. It appears that physiological concentration of dopamine can modulate the activity of 18-hydroxylase enzyme.
In summary, it can be concluded that the in vivo and in vitro studies are compatible with a view that dopamine has a physiological role in the regulation of aldosterone by modulating the activity of 18-hydroxylase enzyme.

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