Our recent studies demonstrated that dopaminergic receptor may play an important. role in controlling blood pressure and renal sodium handling. This study was designed to investigate whether endogeneous Na⁺-K⁺ ATPase inhibitors are related to changes in blood pressure and sodium balance, caused by the administration of metoclopramide (MC), a dopamine (D₂) receptor antagonist, and sodium loading.
Young male Wistar rats (250-300g) were raised under three different conditions, control (control group), 1% NaCl loading (NaCl group) and 1% NaCl plus 1.5mg/kg/day of metoclopramide (MC group) for 7 days. Systolic blood pressure (SBP), urinary and plasma Na⁺-K⁺ ATPase inhibitory activity (ATPI), urinary sodium, potassium and catecholamine excretions were measured.
SBP in the MC group elevated from 116±2mmHg to 134±4mmHg, but there were no changes in SBP in the control and NaCl groups. Urine volume and urinary sodium excretion significantly increased in not only the NaCl group but also in the MC group. Plasma ATPI in both the NaCl and MC groups was higher than in the control group (p<0.001), and the level of ATPI in the MC group was signifiantly higher than in the NaCl group (p<0.05). Urinary ATPI in the control group was not detected after 7 days, but that in the NaCl and MC groups was clearly increased. The excretions of urinary catecholamines remained un changed in all groups. These results suggest that daily sodium intake may regulate the secretion and/or production of endogeneous Na⁺-K⁺ ATPase inhibitors, and that there is some relation of increased Na⁺-K⁺ ATPase inhibitors to elevated blood pressure led to by an antagonist with dopamine during sodium loading.

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In 107 patients with non-insulin dependent diabetes (NIDDM), plasma growth hormone (GH) responses during standard arginine test (0.5g/kg of body weight) were studied and analyzed in comparison with those in 17 normal subjects. The indices of the responsiveness of GH, peak value of GH, sum of GH values (ΣGH), area of GH curve (∫ GH), sum of GH values above fasting level (ΣΔGH) and area of GH curve above fasting level (∫ΔGH) during the test (2hr) were calculated. Data were also analyzed with multiple regression analysis using stepwise method for variable selection.
Basal level of GH was significantly higher in diabetic patients than in normal subjects (2.1±1.7 vs. 1.6±0.5ng/ml, mean±SD, p<0.05), and ΣGH and ∫GH were also higher in diabetic patients. There was a significantly positive correlation between fasting plasma glucose (FPG) and basal level of GH (r=0.24, n=107, p<0.05), and the indices of GH responses except ΔGH and GH peak value (r=0.24 to 0.31, p<0.05 to 0.01). Some indices of GH responses (ΣΔGH, ΣGH, ∑ΔGH and f GH) were significantly higher in the poor control group (patients with FPG above 180mg/d1, n=29) of diabetic patients than in the good control group (patients with FPG below 140mg/d1, n=59), or in the group with no abnormal findings of retinopathy (n=46). During the follow-up of retinopathy for 2.5 years on the average, progression of retinopathy was found in 21 out of 107 patients. Significantly higher GH, and GH in the patients with increasing severity of retinopathy were revealed retrospectively compared to the patients without it. However, there were no significant differences in these parameters between both groups matched by FPG or severity of retinopathy.
Multiple regression analysis to the basal GH level and GH responses during arginine infusion as criterion variables of various predictor variables (total 44 factors : biochemical laboratory data, indices of glucose and insulin response to oral glucose load, indices of glucose response to arginine, age, age of the onset, obese index, duration of retinopathy, neuropathy, and therapy) were performed in 86 patients using forward and backward method for variable selection. Basal plasma level of GH showed close positive association with therapy and proteinuria and negative association with age and obesity. Five of 6 indices of GH responsiveness showed significant relationship with retinopathy. The following significant association was observed : The therapy was significantly related to peak value of GH, LGH and ΣΔGH; FPG to f ΔGH, I ΔGH and f GH; blood pressure to ΔGH and ΣΔGH; sex to ΣΔGH and ∑ΔGH; age, duration of the illness, serum alkali-phosphatase and beta lipoprotein to peak value of GH; serum creatinine and PSP values to f GH.
On the other hand, multiple regression analysis of the above factors of diabetic retinopathy graded by Scott's classification revealed a close positive association with neuropathy, GH responses to arginine and FPG, and negative association with obesity and serum level of alkali phosphatase.
These findings suggest a deficiency of the suppressive mechanism due to raised glucose level of GH response in diabetics, and a strong association of GH response to arginine with the appearance or severe development of retinopathy.

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Uteroglobin (utg) is a potent phospholipase A₂ inhibitor but is genetically distinct from lipocortins. The purpose of the present investigation was to biochemically and immunologically characterize the utg-like antigen from rabbit plasma and serum that were found to be highly positive by radioimmunoassay (RIA).
The RIA standard curve of pure rabbit utg from the uterus is compared with utg-like protein in circulation, and the curves are parallel to each other. Concerning the western blot of utg-like protein as compared with utg standard, it is clear that there is a distinct protein band corresponding to the two monomers of utg (7kDa).
Moreover, the rise in endometrial utg synthesis that occurs upon progesterone (P) treatment in rabbits is paralleled by a dramatic decrease in endometrial PGE₂, PGF_2αlevels.
The level of utg-like protein in circulation increased the level of this protein approximately three-fold in the serum (70ng/ml without Pvs 216 ng/ml with P), whereas dexamethasone (Dex) increased it two-fold.
To determine the source of this protein in circulation, we canulated the uterine and the pulmonary veins of rabbits primed with different steroids. The levels of utg-like protein in the uterine venous plasma versus peripheral venous plasma were as follows : 379 ng/ml vs 216 ng/ml, treated P. The pulmonary venous plasma was compared with the peripheral venous samples (1240ng/ml vs 127 ng/ml, treated Dex).
The results of the present study indicate that utg-like protein is detectable in the circulation of the rabbit.

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Cyproterone acetate (CA), a well-known competitive antiandrogen, has been used for the treatment of precocious puberty, prostatic adenocarcinoma, hirsutism and hypersexuality. However, there have been some reports of troublesome gynecomastia developing during the use of this drug. It was, therefore, of interest to investigate the effect of CA on peripheral aromatization, since it is the major source of circulating estrogens in men. Our recent studies of aromatase activity in human skin fibroblasts demonstrated that the skin is an important site of extraglandular aromatase activity in men and suggested that these cells might provide a valuable new system in which to study the enzyme. Estrogen formation was assayed by the [³H] H₂ O technique, after 3h incubation of the cells with androste-nedione. The initial experiment was designed to test the effect of CA (10^-8 to 10^-5M) on baseline aromatase activity during a 12h preincubation in the presence of fetal bovine serum (FBS). Baseline aromatase activity was not affected by the presence of CA, whereas medroxyprogesterone acetate, a similar synthetic progestogen, induced a 2-fold stimulation of aromatase activity at a concentration of 10^-5M. In cells preincubated with dexamethasone (DEX) in the presence of FBS, aromatase activity was stimulated markedly. When the cells were preincubated in the medium containing FBS with DEX (2.5×10^-7M) in the presence of CA (10^-7to 10^-4M), DEX-stimulated levels of aromatase activity were inhibited by CA in a dose-dependent fashion. A competitive binding assay using [³H] DEX, showed that CA was able to compete with DEX for glucocorticoid receptor and the relative binding affinity of CA was approximately 50 times less than DEX. This suggested that the inhibitory effect of CA was due to competition with DEX for receptor binding. Aromatase activity was also stimulated by (Bu) ₂ cAMP (1mM) in the absence of FBS. The stimulatory effect of (Bu) ₂ cAMP was maximal after 12-24h of preincubation, and this level was maintained for 60h. Similar to the DEX stimulation, stimulation of aromatase activity by (Bu) ₂ cAMP required both RNA and protein synthesis, since the stimulatory effect of (Bu) ₂ cAMP was abolished by co-preincubation with cycloheximide or actinomycin D. When CA was present during either the 12h preincubation or assay incubation, no difference was found in the (Bu) ₂ cAMP-stimulated levels of aromatase activity. On the other hand, the nonaromatizable androgen dihydrotestosterone (DHT) (10^-8 to 10^-6M) inhibited the stimulation of aromatase activity by (Bu) ₂ cAMP in a dose-dependent fashion. The inhibitory effect of DHT on (Bu) ₂ cAMP stimulation of aromatase activity was prevented by co-preincubation with CA (10^-5M). These findings suggest that CA acts to increase aromatase activity in skin fibroblasts by preventing the inhibitory effect of androgen as antiandrogen under physiologic conditions, although CA inhibits the glucocorticoid stimulation of aromatase activity.

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Thirty-eight patients with collagen diseases undergoing chronic glucocorticoid treatment were studied to assess the effect of a 24 month administration of oral 1α-hydroxyvitamin D (1α-OHD), calcium and thiazide on bone and mineral metabolism.
All patients were premenopausal women (mean age = 35 y.o.) and had been treated with prednisolone (mean dose = 11mg/day). Patients were randomly divided into three groups. Fourteen patients were treated with 0.75μg of 1α-OHD and 400mg of calcium daily (1α-OHD group). Eleven patients were treated with 1α-OHD, calcium and 4mg of trichlormethiazide (thiazide group). Thirteen patients did not have any treatment for osteoporosis and served as a patient control group.
There were no significant differences in age, underlying disease, dose of glucocorticoid, or pretreatment values of indices of osteoporosis among the three groups. Twenty-four hour urinary calcium excretion had increased above 300mg/g creatinine at 12 or 24 months after the start of the treatment in 9 patients of the 1α-OHD group, and asymptomatic renal stones developed in 2 of them. However, neither hypercalciuria nor renal stones developed in the thiazide group or the control group. Serum iPTH levels were suppressed significantly in the thiazide group, but did not change in the 1α-OHD group or the control group.
Metacarpal index (MCI) and EGS/D, indices of microdensitometry method which indicate bone mineral content, had significantly increased after 12 and 24 months in the thiazide group, while these indices did not change significantly in the 1α-OHD group and deteriorated in the control group at 24 months. Seven patients of the control group and 4 of the 1α-OHD group showed deteriorations in Singh's grade compared to only 2 in the thiazide group.
Vertebral bone fractures developed in 5 vertebras of the 2 patients in the control group and 4 of the 3 patients in the 1α-OHD group during the 24 months. But none of the thiazide group suffered from bone fractures.
It may be concluded that combination therapy with 1α-OHD, calcium and thiazide is effective in the prevention of glucocorticoid-induced osteoporosis. Long-term administration of 1α-OHD and calcium should be avoided in patients undergoing chronic glucocorticoid therapy because of the risk of the development of nephrolithiasis.

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