Plasma LH, FSH and endogenous LHRH were determined by radioimmunoassay (RIA) when 100 μg of LHRH superanalogue, des-Gly¹⁰ [D-Leu⁶]-LHRH ethylamide (leuprolide) was intranasally administered to both 7 healthy subjects aged 22 to 63 years and 6 patients with various hypogonadism aged 22 to 43 years [2 with anorexia nervosa, 3 with hypophysial hypogonadism and 1 with isolated gonadotropin (Gn) deficiency].
The response of plasma LH after the intranasal administration of leuprolide was observed to be 814±236 (mean±SE) % in the healthy subjects at 2 to 10 hours, and 528±183% in the patients with hypogonadism at 2 to 4 hours. These elevations were observed until 24 hours after administration in both groups. The response of plasma FSH was observed to be 449±99% in the healthy subjects at 3 to 8 hours, and 593±238% in the patients with hypogonadism at 2 to 6 hours. These elevations were observed until 24 hours in the healthy subjects and until 12 hours in the patients with hypogonadism. Furthermore, these responses tended to be higher than those after 100μg intravenous administration of LHRH; LH responded up to 386±50% in the healthy subjects and up to 390±91% in the patients with hypogonadism, and FSH up to 282±38%, 343±90%, respectively.
The elevation of plasma immunoreactive LHRH which was determined using RIA having no immunocrossreactivity with leuprolide (less than 0.01%) was observed at 6 hours after the administration of leuprolide in the healthy subjects (789±497%). On the other hand, the retardation of the plasma LHRH elevation was observed in the patients with anorexia nervosa, and the failure of that elevation was observed in the patients with hypophysial hypogonadism or isolated Gn deficiency.
These results suggest 1) that the intranasal administration of leuprolide may be able to be substituted for the former LHRH test as the stimulation test of gonadotropins, and 2) that the possible role of the delayed elevation of endogenous LHRH after administration of leuprolide in the healthy subjects may be interpreted as a rebound phenomenon after the first suppression by the negative feedback or caused by the prolonged possession of LHRH receptor in gonadotrophs, but further examination is needed to clarify its mechanism.

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A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350g in weight and 50cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140cm.
On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62mm Hg). Serum potassium concentration was 2.9mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449ng/dl), progesterone (178ng/dl), 17-OH-pregnenolone (1613ng/dl), 17-OH-progesterone (180ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7ng/dl), corticosterone (0.65 μg/dl) and cortisol (6.8μg/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH₂0/CH₂O+CCI= 0.62, normal : 0.92±0.04). Moderate hyper plasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney.
Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation.
Treatment with dexamethasone (2mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75mg/day) decreased urinary excretion of prostaglandin E₂ from a high level of 738.4ng/day to 433.4ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low. Although hypokalemia was improved by the administration of potassium chloride (max. 80mEq/day), distal fractional chloride reabsorption was not altered (CH₂O/CH₂O+CCI=0.66).
It is possible that progesterone excess might play some role in the activation of the renin-angiotensin-aldosterone system through its natriuretic effect, which might influence clinical feature of the Bartter's syndrome. However, the finding that metabolic disorders were not improved after dexamethasone therapy suggests that the patient was suffered from not only 21-hydroxylase deficiency but also Bartter's syndrome. It seems likely that the reciprocal translocation has no significance to the pathogenesis of 21-hydroxylase deficiency and Bartter's syndrome. As a final note, the defect in chloride reabsorption may be a primary cause of Bartter's syndrome in this patient.

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Effects of prostaglandin F_2α, E₂, D₂ and J₂ on the DNA and RNA contents of a human endometrial cancer cell lines (SNG and Ishikawa) were studied using flow cytometry.
1) Cytotoxic effects of various prostaglandins on SNG and Ishikawa cell lines were examined and PG J₂ and PG D₂ were found most active. Among other prostaglandins PG E₂ showed a comparable inhibitory activity to cellular growth but PG F_2α didn't.
2) In SNG and Ishikawa cell lines after RNase treatment, PG J₂, PG D₂ and PG E₂ caused a decrease of the S-phase and G₂ M-phase cell population in cell cycle. On the other hand, PG F_2α caused a increase of the S-phase cell population in cell cycle.
Prostaglandins were found that G₀₊₁-phase cell population in cell cycle increased.
3) PG J₂, PG D₂ and PG E₂ after DNase treatment caused a decrease of the relative RNA content in both of cell lines. On the other hand, PG F_2α caused a increase of the relative RNA content.
It is a noteworthy that PG J₂ and PG D₂ were remarkably recognized delay of doubling time and decrease of survival fraction under the time and dose dependence. These effects occure not only by direct lethal influence of the prostaglandins, but also by substantially inhibit RNA and DNA synthesis with a delay of the cell cycle.
These results might be suggested a role for prostaglandin J₂ and D₂ in the regulation of growth of endometrial adenocarcinoma cells.

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Bartter's syndrome (B.S) is often difficult to distinguish from pseudo-Bartter's syndrome (pseudo-B.S), a condition which may be caused by “loop” diuretics abuse.
Although our patient firmly denied ingestion of diuretics or laxatives, all screening of urine samples gave consistently positive results for furosemide, even during hospitalization.
A 25-year-old married woman with peristent hypokalemia had many characteristics of B.S, including hypokalemic hypochloremic alkalosis, hyperactivity of the renin-angiotensin-aldosterone system, normotension, insensitivity to the pressor effect of angiotensin II (A. II), increased urinary excretion of prostaglandin E₂ and kallikrein, and marked reduction of distal fractional reabsorption of chloride in Henle's loop, as estimated by CH₂O/CH₂O + C.Cl, under conditions of hypotonic saline diuresis. Furthermore, hypotension occurred with [1-Sar, 8-Ile] A.II and with the angiotensin converting enzyme inhibitor (Captopril). Renal biopsy revealed juxtaglomerular hyperplasia. A tentative diagnosis of B.S was made. Indomethacin (IDM), an inhibitor of prostaglandin synthesis was prescribed and the pressor response to A.II improved. Impaired fractional chloride reabsorption was also improved significantly under IDM, but the value was low compared to the normal. The value for basal plasma human atrial natriuretic polypeptide (hANP) was slightly above the normal ranges and was suppressed by IDM.
We conclude that manifestations B.S in this patient may have been fostered significantly by the long-term surreptitious use of furosemide, taken to lose weight. The analysis of urine for detection of diuretics was only finding distinguishing her clinical state from “true” B.S and leading to a final diagnosis. Pathophysiologic relationships between B.S and pseudo-B.S due to furosemide are discussed.

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Serum concentrations of total calcium, ionized calcium and inorganic phosphorus in severe PIH were significantly lower than those in normal pregnancy during the 3rd trimester of pregnancy and continued to be low even at puerperium. On the other hand, serum concentrations of parathyroid hormone in severe PIH were significantly higher during the 3rd trimester of pregnancy and decreased at puerperium. Any remarkable differences in serum calcitonin levels were not found between severe PIH and normal pregnancy through the last trimester of pregnancy and puerperium. Serum concentrations of 1α, 25-(OH) ₂vitaminD₃ increased significantly in the 3rd trimester of normal pregnancy, but in severe PIH, their increase was not observed, remaining at the normal levels of non-pregnant women. The kidney functions in the both groups were within the normal limits of non-pregnant women, but placental dysfunction was observed in severe PIH.
These results suggest that the decrease in serum calcium and phosphorus levels might have occurred as a result of the decrease in the absorption of calcium and phosphorus from the intestine due to the decrease in serum 1α, 25-(OH) ₂vitaminD₃ levels and that low serum 1α, 25- (OH) ₂vitaminD₃ concentrations might be caused by the disturbance of the synthesis in the placenta rather than in the kidney.

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Plasma fibronectin (FN) level was determined in normal subjects and patients with thyroid disease by the Laurell method. In vitro effect of triiodothyronine (T₃) on FN synthesis by cultured human fetal skin fibroblasts was also studied. Plasma FN level was 32.2±5.5mg/dl (mean ± SD) in normal adults, and no sex difference was observed. The plasma FN concentrations were increased in patients with hyperthyroidism (63.3±15.2 mg/dl), decreased in patients with hypothyroidism (19.5±6.5mg/dl), and in normal range in patients with simple goiter (30.2±7.0mg/dl). These FN values have been normalized with a time lag of a short period after their thyroid function became normal. There was a positive correlation between plasma FN concentrations and serum T₃ or T₄ concentrations, but a inverse correlation between plasma FN concentrations and serum thyroxine binding globulin or cholesterol levels. In vitro studies revealed that the addition of T₃ to the incubation medium stimulated FN synthesis by human fetal skin fibroblasts at the concentrations between 10^-8M and 10^-6M. These results indicate the usefulness of plasma FN determination in patients with thyroid disease for their management and studying pathophysiology of the disease, and suggest at the fluctuation of plasma FN concentrations in these patients may at least in part due to the effect of thyroid hormone on FN synthesis by the cells.

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