The effect of synthetic [Asu^{1, 7}] eel calcitonin (CT) on phosphorus content in the hepatic bile was investigated in intact and nephrectomized rats. The subcutaneous administration of CT (80 MRC mU/100g BW) produced a significant fall in the serum inorganic phosphorus concentration and a corresponding increase in the amount of phosphorus in the liver and kidney. These changes were observed even at the lowest dose of CT (40 MRC mU/ 100g BW). The phosphorus contents in the spleen, heart, lungs and muscle were not significantly changed by CT administration. CT also provoked a marked elevation of phosphorus excretion into the bile. In nephrectomized rats, CT (80 MRC mU/100g BW) caused a significant decrease in serum inorganic phosphorus concentration and a remarkable increase in liver phosphorus content. CT markedly increased phosphorus excretion into the bile of nephrectomized rats. These results support the theory that the hypophosphatemic effect of CT may be, at least partly, based on its action on liver in addition to kidney. This effect of CT on the liver may be the cause of increased excretion of phosphorus into the bile.

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Quantitative estimations were made of insulin receptors on liver cell membrane of DBA/2 mice infected with M variant of encephalomyocarditis virus. The virus produced an impairment of glucose metabolism on day 3 of infection, which lasted for 5 months. The fasting plasma insulin concentration was markedly decreased on day 14. The specific binding of 125-I insulin to the membrane receptor was significantly decreased on day 3 of infection. The binding inhibitions were stronger in male mice than in females. The number of insulin receptors began to decrease on day 1, was decreased remarkably by day 3, and returned on day 7 to the level before infection. A decrease of receptor affinity was also observed in infected animals. These results seem to show that changes in insulin receptors are one cause of the impairment of glucose metabolism in the initial phase of virus-induced diabetes.

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A long-acting analogue of LH-RH, des-Gly¹⁰-[D-Leu⁶]-LH-RH-ethylamide (TAP-144), was administered once or twice on day 9 of pregnancy by subcutaneous, vaginal, rectal, and nasal routes to rats; the pregnancy-terminating effectiveness of these routes was determined on day 14.
When rats were given a single dose of TAP-144, the ED₅₀, value was 1.2μg/100g body weight by the vaginal route, the effectiveness being 752 and 1, 221 times higher than those by the subcutaneous and rectal routes, respectively. Nasal administration was not effective in terminating pregnancy even at a high dose of 2, 000μg/100g body weight. The addition of a surfactant (BL-9) did not increase the effectiveness by the rectal route.
When TAP-144 was administered twice a day, the effectivess was markedly increased by every route. The ED₅₀ values were 0.32μg/100g body weight/time by the subcutaneous route, which was comparable to that of the vaginal route, 14.2μg of the rectal route, and 84.6μg of the nasal route. The addition of the surfactant increased the effectiveness 26 times by the nasal route but not by the rectal route.
The pregnancy-terminating effect of TAP-144 was reversed by treatment with progesterone.

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HLA-A, -B, -C and -DR specificities were determined to study the association of HLA in 49 unrelated patients with Hashimoto's thyroiditis and 51 patients with Graves' disease. The results were compared with 144 control subjects from the Japanese population at large. Much less HLA-DR2 was found in the patients with Hashimoto's thyroiditis than in the normal controls. It was present in 16% of the thyroiditis patients compared to 39% in the controls. Also the frequency of HLA-DR1 was less in the patients with Graves' disease (0%) than in the controls (15%). No positive association was found for any HLA-antigens in the two diseases.

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The initial rate of lecithin: cholesterol acyl transferase and serum concentration of lipids were determined in euthyroid, hypothyroid and hyperthyroid subjects.
In hyperthyroid subjects, the serum levels of total and free cholesterol were significantly lower than in normal subjects and the fractional lecithin: cholesterol acyl transfer rate was significantly higher than in normal subjects. The molar lecithin: cholesterol acyl transfer rate was also higher than in normal subjects, but not significantly.
The free cholesterol/total cholesterol ratio in hypothyroid females and the serum levels of triglyceride and free fatty acid in hypothyroid male were significantly higher than in normal subjects. The fractional lecithin: cholesterol acyl transfer rates in hypothyroid females were significantly lower than in normal females.
After treatment of the thyroid disease the fractional and molar lecithin: cholestorol cholesterol acyl transfer rate approached the normal values. There was a positive correlation between fractional and molar lecithin: cholesterol acyl transfer rate and thyroxine.
These results suggest that thyroid hormone influences the cholesterol esterification through the activation of lecithin: cholesterol acyltransferase.

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The mode of involvement of sex steroids in the growth spurt during adolescence was studied in Wistar rats with a special reference to the level of serum somatomedin A (SMA) determined by radioreceptor assay. Intramuscular administration of testosterone propionate (T; 1 mg/day, alternately for 10 days) to female or gonadectomized male rats provoked a small but significant increase in their body weight or body length without affecting the serum SMA level. In contrast, in hypophysectomized (hypox) male rats T caused a considerable increase in body weight and the serum SMA level only when administered concurrently with bovine growth hormone (bGH; 0.2 U/day, ip). T did not affect the sulfation activity in vitro. These results suggest that androgen participates in the growth spurt during adolescence by enhancing the SMA effect and/or potentiating the SMA production by GH.
Estradiol benzoate (E₂;100μg/day, alternately for 10 days) caused a decrease in the serum SMA level and the growth rate in normal male rats. However, E₂ produced an increase in the SMA level when administered to hypox male rats, although the growth was retarded and sulfation potency of the serum was sharply reduced. These results indicate that E₂ may suppress the growth by lowering SMA generation in normal rats and cause a production of biologically inactive SMA in hypox male rats.

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Medullary and cortical tubular cells were prepared from rat kidneys with collagenase treatment. Arginine vasopressin (AVP) stimulated cyclic AMP production both in medullary and cortical cells with a dose-response relationship at concentrations ranging from 10μU/ml to 10 mU/ml, whereas parathyroid hormone (PTH) and calcitonin did only in the latter. Using this medullary cell system, effects of acute changes in endogenous plasma AVP levels in vivo on its cyclic AMP responsiveness to AVP (10 mU/ml) in vitro were examined. Acute elevation of plasma AVP levels induced by ip injection of 20%(w/v) polyethylene glycol-isotonic saline solution 3 h prior to sacrifice resulted in a 33% decrease in cyclic AMP responsiveness to AVP (desensitization). More prolonged elevation of plasma AVP levels by water restriction for 48 h, on the other hand, increased the responsiveness by 38 to 81%, which was restored to basal levels by ad libitum intake of water for another 48 h (positive feedback regulation). These maneuvers did not alter the cyclic AMP responsiveness to PTH (10μg/ml) in cortical cells.
The results suggest that AVP-stimulated adenyl cyclase in rat renal medulla may be regulated by changes in endogenous AVP levels even within the physiological range.

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Changes in progesterone (P), 20α-dihydroprogesterone (20α-OHP), testosterone (T) and estradiol-17β(E2) in peripheral blood, in corpora lutea (CL) of pregnancy and lactation and non-luteal ovarian tissues (NLO), and serum levels of LH, FSH and prolactin (PRL) were determined by radioimmunoassay in lactating rats nursing 8 pups. CL of pregnancy and lactation and NLO were removed at various days after post-partum ovulation (Day 0 of lactation=day of parturition).
Serum E₂ remained low until Day 10 of lactation followed by a slight increase from Days 12 to 21. Serum T was unchanged throughout lactation. Low levels of T and E₂ in NLO were observed until Day 12, followed by a gradual increase on Day 15 and onward. These changes correlated with low levels of serum LH from Days 2 to 12 and a return to basal levels on Days 15 to 21. Throughout lactation serum FSH remained at basal levels corresponding to diestrous values during the estrous cycle. High levels of serum PRL were observed from Days 4 to 10. Serum levels of P reached maximal values between Days 8 and 10 and decreased after Day 12. Changes in serum 20α-OHP were inversely related to serum P throughout lactation. The CL of pregnancy contained large amounts of 20α-OHP and small amounts of P on Days 1 and 2 followed by an abrupt decline until Day 21. On the other hand, a marked increase in content and concentration of P in the CL of lactation occurred between Days 6 and 12 followed by a gradual decline by Day 21. Content and concentration of 20α-OHP in the CL of lactation increased progressively from Day 1 to 21.
These findings indicate that the CL of pregnancy secrete a large amount of 20α-OHP and a small amount of P during the early stages of lactation. Thereafter, the CL of lactation markedly increase their ability to secrete P. High levels of P and PRL during the first half of lactation along with strong suckling stimuli may be involved in the suppression of follicular development, presumably by lowering basal levels of serum LH.

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To study 5α-reductase activity in the human fetal tissues, hypothalamus, cerebrum, skin, liver, kidney, small intestine, lung, adrenal and placenta of aborted fetuses at mid gestation were obtained and incubated with labeled Δ⁴-3-keto steroids under CO gas in the presence of excess NADPH.
A higher conversion of progesterone to 5α-pregnanedione was observed in the hypothalamus and cerebrum than in other tissues studied. The major portion of 5α-reductase in the cerebrum was localized in 800×g precipitate (crude nuclear fraction). Androstenedione and progesterone were found preferred substrate for 5α-reductase to 17α-hydroxyprogesterone or testosterone. Km of 5α-reductase for progesterone and androstenedione were 1.0×10^-5 M and 9.0×10^-6 M, respectively. The enzyme activity for progesterone was inhibited by estrone and androstenedione but not by estriol.

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Relationship between forebrain lordosis inhibiting system and serotonergic mechanism was examined in estradiol benzoate (EB) and progesterone (P)-primed ovariectomized rats. In order to remove the forebrain inhibition of lordosis response, anterior roof deafferentation (ARD) which interrupts the dorsal inputs to the POA coming down anterior to the anterior commissure or medial preoptic area lesions (POA-L) were made. All experimental females pretreated with EB and P showed high levels of lordotic activity. Soon after the behavioral tests, the animals were injected with 10 mg/kg p-chloroamphetamine (PCA) intraperitoneally and tested again 30 min later. PCA strongly suppressed female sexual behavior. Regardless of the presence of ARD or POA-L, no PCA injected females showed lordosis. From these results, it can be said that serotonin may not directly act on the forebrain lordosis inhibiting system.

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A case of hypersensitivity reaction to 1-desarnino-8-D-arginine vasopressin (DDAVP) as observed in a patient with diabetes insipidus is reported. This patient was successfully treated with conventional doses of DDAVP after receiving gradually increasing doses.

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³⁵S incorporation into embryonic chick pelvic cartilage was measured using the method of somatomedin bioassay and the effects thereupon of the bovine parathyroid extract (PTE) and the synthetic [Asu^{1, 7}]-eel calcitonin (CT) were examined. Bovine PTE potentiated ³⁵S incorporation stimulated by normal human serum.[Asu^{1, 7}]-eel CT did not affect the sulfation activity in the presence of normal human serum. However, it showed a slight stimulation of ³⁵S incorporation in the absence of normal human serum. No definite interaction on ³⁵S incorporation between PTE and CT was observed. It is speculated from these results that PTH may be involved in the stimulation of the cartilage growth in concert with somatomedins in vivo.

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Melatonin injection either in the morning or in the evening decreases spermatogenesis as well as the Leydig Cell nuclear area in toad, whereas if administered twice daily (morning+evening) it shows no such effect.

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A highly sensitive and specific radioimmunoassay for kinin (minimal detectable amount, 0.5 pg/tube) was applied to measure the blood kinin level. A five ml blood ample was collected with a siliconized needle and plastic syringe which contained 2.5 ml of 0.8 N-HCl. The blood kinin was extracted with butanol, following reextraction with water. According to this procedure, the mean recovery (mean±SE) calculated from added¹²⁵I-bradykinin (500 CPM) and the known amounts of cold bradykinin were 50.4±0.8% and 51.1±2.2%, respectively. In comparison with other sampling methods in 6 normal subjects, the blood samples taken without HCl in syringes showed a higher level (24.4±10.1 pg/ml) than the samples with HCl (5.3±1.3 pg/ml). And very high levels were obtained in the plasma samples collected by the method of Talamo or Vinci (0.53±0.24 ng/ml and 3.5±1.3 ng/ml, respectively).
The kinin content in blood samples taken with HCl was stable at -20°C for at least one month, but increased significantly at room temperature or 4°C for 48 hours, Blood samples were obtained from 17 normal subjects, and 3 patients with acute myocardial infarction. Blood kinin levels in the patient with acute myocardial infarction, 121±20.g Pg/ml, were significantly higher than those in normal subjects (3.8±0.5 pg/ml).
From these results, it was concluded that high levels of blood kinin reported previously may have resulted from inadequate sampling procedures. Thus, in order to measure blood kinin accurately, inactivation of the kinin generating and destroying enzymes must be done immediately after the sampling.
In addition, this radioimmunoassay method should be very useful in investigating the pathophysiological role of blood kinin in various diseases.

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Thirteen patients with moderately severe ophthalmopathy due to Graves' disease were treated by steroid therapy, supervoltage orbital radiotherapy, plasmapheresis and thyroxine replacement. All patients complained of chemosis, ocular pain and diplopia. The mean value of proptosis was 21.3 mm. Eleven patients (84.6%) showed some improvement, but the effect was mostly on the symptoms of orbital soft tissue involvement. The effect on proptosis was rather unsatisfactory. In six patients (46.2%) proptosis decreased by 2.3 mm on the average, but they still had more noticeable exophthlamos than patients with Graves' disease without infiltrative ophthalmopathy. For regression of proptosis, radiation therapy was the most beneficial therapeutic regimen in this study, especially in the patients who received the treatment shortly after the beginning of malignant exophthlamos.

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