The effects of adrenalectomy, ether-laparotomy stress and in vivo administration of either ACTH or dexamethasone on the cAMP levels in the anterior pituitary and the adrenal glands were investigated in male rats. After adrenalectomy or ether lanarotomv stress, an increase of the pituitary cAMP levels was observed. A prior administration of dexamethasone failed to inhibit the increase of the pituitary cAMP levels. Acute administration of dexamethasone increased the cAMP levels in the pituitary. Chronic administration of dexamethasone decreased the cAMP levels in the pituitary, but ACTH did not. These data suggest that cAMP might be involved in the mediation of the hypothalamo-pituitary-adrenal axis.

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Prolactin iodinated by lactoperoxidase method showed immunologically, electrophoretically and biologically similar properties to native prolactin and possessed enough specific radioactivity for receptor studies.¹²⁵I-prolactin was incubated with mouse mammary tissues at 8 days of lactation. Both binding and release of¹²⁵Iprolactin depended on incubation time and temperature and were maximal at 37°C. Michaelis constant was estimated to be 1.4×10^-9 M from Lineweaver-Burk plot and to be 1.2×10^-9 M from mid-value of the dose-response curve for displacement with native prolactin. Total number of binding sites for prolactin was 1.38×10^-15 mole per mg weight of tissue. Ovine prolactin, human growth hormone and human placental lactogen competed with ¹²⁵I-prolactin and dose-response curves for these three hormones were all parallel. These results suggest the existence of a specific receptor site with high affinity for prolactin in lactating mouse mammary glands.

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The effect of excess iodide on hog thyroid gland has been examined with regard to the change in the chemical composition of thyroglobulin and in the accumulation of 27-S iodoprotein by the in vivo treatment of hogs with iodide for various lengths of time.
The iodine content of thyroglobulin was either unchanged by short term administration of excess iodide, or somewhat lowered. However, the iodine content as well as the total amount of thyroglobulin increased in the glands enlarged by prolonged treatment with iodide. The iodine highest reached 1.17% of the protein on an average. On the other hand, 27-S iodoprotein decreased and finally disappeared after the chronic treatment.
Monoiodotyrosine and diiodotyrosine increased in parallel with the increase in the iodine content (0.15 to 1.17%) caused by the iodide treatment, while thyroxine increased but reached a plateau at the level of three residues per mole of thyroglobulin, and no change was observed even in the proteins with the higher iodine content than 0.75%.
Proteolytic activity measured by amino acid release from the thyroid protein was depressed by the chronic treatment. On the other hand, the amount of iodocompound released by the autoproteolysis, which may reflect hormone secretion, increased, possibly because of the marked increase in the iodine content of thyroglobulin.

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The effect of a 4-week diet regulation on non-obese, adul-onset diabetics was studied. The diet, which was prescribed for them, was composed of 60% carbohydrate, 15-20% protein and 20-25% fat. The total caloric intake was restricted to 30, 35 and 40Cal/kg ideal body weight depending on their physical activity.
In the group whose calculated diet showed over 10% reduction in total caloric intake and carbohydrate intake, fasting glucose was decreased and glucose tolerance was improved significantly after the 4-week dietary therapy. Insulin response to oral glucose loading was improved, particularly in the later stage of oral glucose tolerance test. As a result, insulin area, i.e. the total area under the insulin curve was increased to almost two times. The sensitivity to insulin did not show any significant changes after diet regulation.
The present data indicate that the therapeutic effect of the diet restriction should be at least in part ascribed to the increased secretion of insulin. In the treatment of diabetics, a restricted diet is essential and beneficial from the point of view that it could improve the pancreatic, β-cell function.

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Electrolytic lesions were placed in the preoptic area or in the middle and posterior hypothalamus of female rats within 48 hrs after birth. Vaginal opening was delayed significantly in rats having the medial preoptic area (mPOA) destructed as compared to sham-operated animals and those given lesions in the other parts of the hypothalamus. Only rats with the mPOA completely destructed developed the anovulatory syndrome. In these animals, unilateral ovariectomy was not followed by enlargement of its fellow. The present results are not in agreement with those of previous workers that electrolytic destructions of the diencephalon induced precocious puberty. The difference may be ascribable to difference in size and locus of lesions.

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A calcium ionophore (A-23187, 20μg/ml) stimulated¹⁴C-1-glucose oxidation in dog thyroid slices to an extent equivalent to that obtained by the optimal concentration of dibutyryl cyclic AMP (1mM). Furthermore, the ionophore augmented the stimulation by dibutyryl cyclic AMP much more than the simple additive effect. The ionophore also enhanced the effect of TSH, but to a lesser extent.
Under conditions where organic binding was blocked, T/M ratio of radioiodine concentration was lowered in slices by the ionophore; the findings similar to those obtained with TSH and dibutyryl cyclic AMP.
The ionophore exhibited a slightly depressive effect on the basal cyclic AMP level. The elevation by TSH of cyclic AMP levels was also slightly depressed by the ionophore, but statistically insignificant in most cases.
These results indicate that calcium ion may play an important role in the TSH regulation of iodide transport and glucose metabolism in the thyroid, in some cases by augmenting the effects of cyclic AMP.

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A sensitive and reliable radioimmunoassay for human calcitonin was described and applied to preliminary clinical studies.¹²⁵I-labelled synthetic human calcitonin M was purified by gel filtration with Sephadex G-25 and G-100. A nonequilibrium incubation system was applied at the final volume of incubation mixture of 500μl, in which pooled plasma from normal subjects or hormone free serum was used as carrier protein at 20% incubation mixture. Dextran T 40 coated charcoal, resuspended in 1% bovine serum albumin buffer, was used for the separation of free from bound tracer. This showed the least nonspecific adsorption of tracer to charcoal. The assay was sensitive to 0.1ng per milliliter of plasma. Recovery of synthetic human calcitonin added to plasma was found to be 101%(S.D., ±8). Diluted plasma from a patient with medullary thyroid carcinoma showed a dilution curve parallel to standards. Basal calcitonin levels were less than 0.3ng/ml in normal subjects. Relatively high values were found in patients with chronic renal failure and in patients with malignant tumors. Extremely elevated values were found in patients with medullary thyroid carcinoma. Provocative calcium infusion tests were also performed.

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Cohn's fraction IV-4 of human plasma protein generates by itself a substance with slight pressor activity when incubated without any additives. This renin-like activity was readily inactivated by alkaline treatment. Furthermore, the generated pressor substance, when purified, was found very similar to [Asp1]-[Ile⁵]-angiotensin-I in the following characteristics;1) heat-stability, 2) dializability, 3) inactivation by trypsin, 4) R_f value and 5) electrophoretic mobility at various pHs, 6) marked enhancement in pressor and oxytocic activities after incubation with normal human plasma or rabbit's lung extract, and 7) cross reactivity with [Asp1]-[Ile⁵]-angiotensin-I in radioimmunossay.
It is concluded that renin-like activity in the preparation of fraction IV-4 of human plasma protein must be renin or an extremely similar enzyme.

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Treatment of cytosol from the rat ventral prostate with cold acetone (-20°C) evoked a 8-10-fold increase in the binding capacity with 5α-dihydrotestosterone (DHT). Starting from the extract of acetone-dried prostate cytosol, some 400-500-fold purification of the DHT-binding protein complex was achieved by (NH₄) ₂SO₄ fractionation, DEAE-cellulose chromatography and gel-filtration with Sephadex G-200. The purified ³H-DHT-binding protein complex was incorporated into the nuclei from the ventral prostate in a temperature dependent manner. The similar incorporation was also observed in nuclei from the liver and the kidney. Separation of prostate nuclei into subnuclear fractions revealed that the majority of the incorporated ³H-DHT-binding protein complex was located in the fraction of heterochromatin and a relatively small amount of ³H-DHT-binding protein complex was observed in the fraction of nucleolei. A slightly different pattern of distribution of 3H-DHT-binding protein complex among subnuclear fractions was observed in nuclei from rat liver.

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A new technique to measure the uro-genital parameters such as the lengths of urovaginal septum, corpora cavernosa and anogenital distance on the sagittal sections of the pelvic region of female fetus of rat under microscope equipped with a micrometer was developed. In the examination of 180 normal female fetuses on the 21st day of gestation, relationships were observed between the fetal body weight and the length of urovaginal septum as well as anogenital distance, but not on the length of corpora cavernosa.
Following maternal subcutaneous administration of various doses of 17α-methyltestosterone between the 17th and 20th day of gestation, dose-dependent abridgment in urovaginal septum length and extensions in corpora cavernosa length and anogenital distance were observed in female fetus on the 21st day's examination. When these three parametars were calculated on the relative value to the fetal body weight, however, linear relationships against log-dose were observed in all parameters. Among these three parameters the abridgment in urovaginal septum was shown to be the most sensitive.
A quantitative assay of virilizing activity of steroids in female fetuses was examined on rats treated subcutaneously with 17α-methyltestosterone and norethandrolone. Linear regressions against the log-doses of both steroids were demonstrated in urovaginal septum length, and parallelism was noted between both regression lines. The relative potency of norethandrolone to 17α-methyltestosterone calculated on urovaginal septum length was 0.354 with fiducial limits of 0.293-0.446, and it was suggested that the virilizing activities of steroids can be evaluated quantitatively.

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From the human cervix uteri under various conditions, structural glycoprotein was isolated which had a remarkable resemblance in its amino acid composition to other connective-tissue glycoproteins found in mammalian tissue. It was corroborated that the amount of such a structural glycoprotein increased in pregnancy, whereas collagen content was higher in the nonpregnant control. These facts suggest that the lost collagen was replaced by those structural glycoproteins in pregnantc ervix uteri. The possible significance of those structural glycoproteins on cervical dilatation is discussed.

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Androsterone, etiocholanolone, pregnanetriol, dehydroepiandrosterone, pregnanediol, tetrahydrocortisol, 5-pregnenolone and 11-β-OH-androsterone were incubated with β-glucuronidase preparations (Helix pomatia, bovine live and E. coli) for 96 hrs at 37°C. After extraction and silvlation they were gas-chromatographed. The first 3 steroids were left practically intact. The least decomposition of the last 5 steroids occurred with the liver enzyme. Testosterone and 11-ketoandrosterone without the enzymes showed 74 and 35% recoveries. Cortisol and tetrahydrocortisol, incubated with the first two enzymes for 18hrs at 37° and 48°. showed nearly 100% recoveries. The recoveries of 17-OHCS in urines (pH 7.8-8.8), stored for 7 days, was 80% at 20°-25°C and 55% and 55% at 25°-30°C. The same samples, brought to pH 1.8-2.8 with NaHSO₄ before the storage, showed a 100% recovery.

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The rats brought up under continuous illumination from the neonatal day persist in the rhythmic estrous cycle for long time and do not easily reveal so-called continuous vaginal estrus. On the contrary, immature rats at about 30days of age show the persistent estrus soon after exposure to continuous illumination as well as adult rats. The purpose of this paper was to examine the relation of the age placed under continuous illumination and the time required to reach the persistent estrus. As the results, it was found that the younger rats need proportionally the longer time to reach the persistent estrus; the rats which were transferred into continuously illuminated environment at 0 (group A), 5 (group B), 10 (group C), 15-16 (group D) and 30 (group E) days of age required a mean time of 132.1±8.4, 126.8±8.9, 89.7±6.2, 91.5 ± 3.8 and 70.3±3.0 days after birth to reach the persistent estrus, respectively. In the present data, a significant difference was seen between group B and C. Though all rats were killed after the same length of persistently estrous periods, actual endocrine level appeared to differ among the groups; the rats required longer time to reach the persistent estrus had smaller ovaries and adrenals.

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Intramuscular injection of 100mg of sulpiride significantly raised plasma human prolactin (hPRL) levels in all of 7 normal subjects examined. The mean (±SE) peak value was 78.0±16.6ng/ml, which was observed 30min after the injection. Daily administration of sulpiride (50mg tid po) raised plasma hPRL levels in all 7 patients with peptic ulcer, with peak values obtained within 2weeks. Lactation occurred in 2 of these patients. It is concluded that sulpiride stimulates hPRL secretion in man.

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To reconcile the knowledge on tissue T3 concentration with cellular metabolism or regulatory mechanism of thyroid hormone secretion, the pattern of the change of tissue T3 concentration following an acute administration of T3 was studied in mice. Basal T3 concentration in serum, liver, brain and pituitary was 61, 173, 198 and 1630ng/100 g, respectively. After 0.5μg T3 dose, T3 concentration in serum and liver reached the maximum level 1 to 3 hrs following the administration and decreased exponentially thereafter, thus, maintaining almost constant tissue/plasma T3 ratio. In contrast, T3 increase in brain or pituitary was far delayed, not until 7 to 12 hrs following T3 injection, and then decreased parallel to that in serum. Furthermore, the magnitude of increase in pituitary T3 was limited when compared to that in liver. Thus, tissue/plasma T3 ratio in pituitary decreased markedly after the dose of T3. This finding suggests the possibility that there is blood-brain barrier or blood-tissue barrier for the transport of T3 in pituitary or brain, resulting in delayed equilibrium with that in serum. These results may also explain the delay of inhibition of TRHinduced TSH release after single dose of T3 as recently reported by Azizi et al.(1975).

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Mouse prolactin was purified by organ culture of pituitaries and electrophoresis of the medium. Mouse pituitaries were organ-cultured in 9-cm Petri dishes containing Waymouth's medium (MB 752/1) supplemented with penicillin (50units/ml), streptomycin (100μg/ml), and bovine insulin (0.12 I.U./ml) for 8 days. Prolactin-rich culture medium was half-saturated with ammonium sulfate and centrifuged. The pellet was subjected to analytical disc electrophoresis (10% acrylamide). Gels were sectioned into 2-mm segments. Prolactin was eluted in 0.04M phosphate buffer (pH 7.2), dialyzed and lyophylized. Two hundred and forty ml medium in which 360 pituitaries were cultured yielded 29.3mg lyophylized mouse prolactin. Although the preparation contained 2 other bands on acrylamide gel disc electrophoresis, a single precipitin line was seen in immunodiffusion and immunoelectrophoresis, showing the identity of their antigenicity. From these results, two other proteins in the preparation were suggested to be deamidated prolactin.

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