Adult C₅₇Bl/Icrc female mice were given a single total body dose of 300r X-rays. They were mated with non-irradiated litter-mates and the progeny maintained over several generations. Some of the females of the 17th generation of this population gave birth to litters with phenotypic characters different from the original parents. At maturity the total gonadotrophins of the pituitaries of these animals were estimated by bioassay. It was found that the hypophyseal complement of gonadotrophins in these mice is significantly higher as compared to the values for the strain of their parents at identical age. The possible implications of this finding on the endocrine physiology of this new population of mice is discussed.

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Effects of the uterine cervical stimulation applied at the postpartum estrus was examined in the lactating rats whose pups were removed on various days from 0 to 26 day after parturition. The changes of vaginal smear and the secretion pattern of progestins were followed. In the animals either with (experimental group) or without (control group) the stimulation, the continuation of lactation beyond 24 days after parturition caused the appearance of vaginal estrus. With the shorter lactation periods, however, vaginal estrus appeared only after weaning, and the average date of appearance was about day 3 of post-weaning in the control and day 13 in the experimental group. The length of the post-weaning diestrus in the experimental group coincided with that of pseudopregnancy. The secretion pattern of progestins also strongly suggested that pseudopregnancy had initiated at the time of weaning. If this was the case, the effect of the cervical stimulation would be carried over through the lactation period.
Contrary to the post-weaning secretion patterns of progestins, those of the lactation period were quite similar in both groups. Terefore, the difference of the post-weaning life span of the corpora lutea between the experimental and control groups could not be attributed to the amount of progesterone secreted at the time of weaning. From the results of the daily inspection of the ovaries and tubal ova, it was concluded that the corpora lutea existing during the post-weaning diestrus were formed at postpartum ovulation and an alternation of corpora lutea was not seemed to take place.

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The effect of electrical stimulation of the medial preoptic area (MPO) on integrated multiple unit activity (MUA) in the arcuate nucleus (ARC) during the estrous cycle of the Wistar rat was examined with reference to the release of “the ovulating hormone” from the anterior pituitary gland. The electrical stimulation (0.5ms, 200Hz, SW, 100-500μA) was applied for 30min between 14:00 and 16:00 under pentobarbital anesthesia. 1) When the stimulus induced ovulation on the following day, MUA changes in the ARC were observed during the electrical stimulation on the day of proestrus, in contrast to their appearance after the electrical stimulation on the day of diestrus II. 2) The electrical stimulation facilitated the release of “the ovulating hormone” on the day of proestrus, while on the day of diestrus II it increased pituitary potency to induce ovulation as well, tested by an injection of a crude extract from the anterior pituitary of the experimental animals into recipients of diestrus II. 3) The circulatory level of the luteinizing hormone (LH) elevated immediately after the electrical stimulation, reached the maximum level 30 min later and returned to the control level after 60min on the day of proestrus. However, on the remaining days of the cycle it elevated immediately, reached the maximum level at 60min, but did not return to the control level even 120min after the electrical stimulation.
Therefore, that the electrical stimulation of the MPO induces neural excitation of the ARC and increase of LH content in the circulation with a discrepancy in the timing throughout the cycle, indicates that the stimulation induces both synthesis and release of LH in the pituitary gland.

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The effect of the suckling stimulus on the acetylcholinesterase (AchE) activity was determined in the whole hypothalamus, the anterior and posterior parts of the hypothalamus in lactating rats. On the morning of the 7th or the 8th day of lactation, the mother was isolated from her young for 8hr. Then, eight pups were placed with the mother and allowed to suckle. The time when the mother was reunited with her pups was designated as zero time of suckling. The animals were guillotined at 2, 5 and 15min of suckling. The AchE activity was measured colorimetrically. Suckling for 2min induced a significant decrease in the AchE activity in the anterior part of the hypothalamus. Thereafter, the activity was restored gradually and returned to the pre-suckling level at the end of the 15min-suckling period. A similar trend was found in the changes of the activity both in the posterior part of the hypothalamus and in the whole hypothalamus, although the changes were not significant. These results suggest that a cholinergic mechanism in the anterior part of the hypothalamus relates with the release of oxytocin in response to the suckling stimulus.

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A transplantable thyrotropic pituitary tumor (TtT 97) in mice and its responsiveness to thyroxine were studied by electron microscopy.
The secretory granules in the tumor cells of the dependent variant were usually more abundant than those in the autonomous tumor cells. In a response to thyroxine, the secretory granules in the dependent tumor cells were initially increased but subsequently decreased in number. In the autonomous tumor cells, no changes were observed after thyroxine treatment.
A few cells containing larger secretory granules were incidentally found in the dependent variant which showed a marked gonadotropic activity. It is therefore suggested that the thyrotropic pituitary tumor of mice might be another example of a mixed tumor, leaving many questions to be answered.

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Distribution of monoamine oxidase (MAO) was histochemically determined in the hypothalamo-hypophysial region of the dogfish, Triakis scyllia. MAO positive neurons, which seemed to be monoaminergic, were observed in the nucleus medius hypothalamicus (NMH) and the nucleus tuberis (NT). NMH was mainly innervated by the MAO-positive fibers arising from the tractus strio-thalamicus et hypothalamicus, and NT was innervated by those from the commissure pre-infundibulaire.
The median eminence was innervated by MAO-positive fibers from both NMH and NT, and these were more abundant in the posterior region. These fibers tended to accumulate around the blood capillaries of the primary plexus. The possibility of the involvement of a monoaminergic mechanism in controlling the secretion of adenohypophysial hormones is discussed.
In the neurointermediate lobe, MAO-positive fibers were often observed between the cells of this lobe. The cylindrical cells around the sinusoid-like capillaries showed rather moderate MAO activity. The cells in the cellular cord of each lobule showed very weak activity. MAO positive cells were also observed in the pars distalis.

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Changes in plasma cortisol concentration and the rate of intestinal water absorption in vitro were examined at intervals after transferring the eel from fresh water to sea water and after treating the freshwater eel with ACTH or cortisol. When eels were transferred from fresh water to sea water, plasma cortisol level increased temporarily after 2 to 4 hr. The highest concentration observed 2 hr after transfer was 9.6±1.6μg/100ml; after 24hr, the concentration returned to the initial freshwater level (3.8±0.9μg/100ml). On the other hand, the increase in the rate of water absorption in the gut was observed 12hr after transfer, and maximum increase was attained after 48 hr. Thereafter the intestine maintained a higher rate than that of the freshwater eel. Essentially similar changes in plasma cortisol and intestinal water flux were observed in the freshwater eel injected with ACTH or cortisol; maximum cortisol level was observed 1-2hr after injection, and intestinal water flux increased maximally after 24 hr, although the highest concentration of cortisol was about 20, μg/100ml, and intestinal water flux returned to the initial level 7 days after the injection. These results indicate that the increased rate of water absorption in the seawater eel is induced by the short-term increase in circulating cortisol. Furthermore, the delayed and prolonged response of the gut to circulating cortisol suggests involvement of some metabolic process for induction and maintenance of increased rate of water absorption in the eel gut in sea water.

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The local effects of estradiol benzoate (EB) on mammary growth were investigated. The pellet of EB mixed with cholesterol at several ratios was implanted in the fat pad of the right third thoracic gland of the ovariectomized 3-month-old Sprague-Dawley female rat. The contralateral gland was served as the control. All the rats given EB pellets showed estrous smears for several days and subsequently continued diestrous smears. Seven-10 days after the onset of diestrus, some rats were killed by decapitation. The other rats were further grafted with the isologous pituitaries under the right kidney capsule and were killed after 20 days. By the observation of the whole mount preparation and the determination of mammary DNA, the mammary gland was found to be promoted in the growth only around the implanted pellet in the rat bearing both EB pellet at the ratio of 1:5, 000 and graft of 2 pituitaries. On the other hand, at all dose levels examined, EB implant alone did not induce mammary growth. These results indicate that EB increases the mammary response to pituitary mammotropic hormones even in its amount which did not promote by itself the mammary growth at all, and provide evidence that one of the actions of estrogen on mammary growth is to sensitize the gland to pituitary mammotropic hormones.

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Clinical features in relation to adrenocortical pathology were described in 9 cases with primary aldosteronism with the following conclusion.
When an adenoma was defined as a benign tumor being completely encapsulated, single adenoma was found in 2 cases and adenomatous hyperplasia in 7 cases. Clinical characteristics were indistinguishable between the cases with adenoma and adenomatous hyperplasia. A complete remission of the syndrome occurred in all cases following unilateral adrenalectomy. There was no marked hypoaldosteronism occurring after the surgery. Histological findings of the adrenocortical tissues surrounding adenoma or adenomatous hyperplasia and in the contralateral adrenal gland were of diffuse or micronodular hyperplasia.

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During past several decades, a variety of bioassay procedures for prolactin has been developed, but preference between each procedure was not yet precisely demonstrated. Therefore following experiments were carried out by using rabbits, mice, rats and pigeons.
In vivo mammary gland assays, such as systemic and intraductal injection into pseudopregnant rabbits, were revealed insensitive, variable and laborious. Minimum effective doses were 1 IU of prolactin in systemic injection and 0.5 IU in intraductal injection. But there were no different findings between 1 and 8 IU in systemic, and 0.5 and 3 IU in intraductal injections.
Prolactin has a luteotropic action in some animals. Corpus luteum cell nuclei (CLCN) of immature hypophysectomized rats were counted after PMS, HCG and prolactin were treated for 10 days. Prolactin stimulate growth of CLCN and therefore numbers of CLCN decreased per unit area. Prolongation of diestrus and positive reaction of deciduomata were observed in mice following prolactin injection, but they were not so sensitive and stable as pigeon assay.
β-glucuronidase activity of rat testis were also revealed to be not sufficiently enough to detect small amounts of prolactin.
Pigeon crop-sac assays are available for prolactin assay. The response to systemic injection could be quantified but sensitivity was not enough to detect 0.01 IU of prolactin.
The injection schedule of twice a day for 2 days was most sensitive in case of intradermal administration. Several assay procedures, such as response diameter, area, dry weight of stimulated area and dry weight of mucosal epithelium, were compared, and dry weight of mucosal epithelium was found to be most sensitive and stable for prolactin bioassay.
From the results mentioned above, it may be concluded that Nicoll's method which measure dry weight of pigeon crop-sac mucosal epithelium is the best bioassay procedure for prolactin determination.

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Porcine calcitonin was administered intramuscularly at doses of 4.5-10MRC u. per day to patients with metastatic bone carcinoma, osteoporosis and polyostotic fibrous dysplasia during 22-50 days period. Transient effects of calcitonin were also investigated in hypercalcemia of primary hyperparathyroidism, multiple myeloma and vitamin D intoxication.
Serum calcium and/or magnesium showed gradual decrease during the period of administration in metastatic bone carcinoma, senile osteoporosis and polyostotic fibrous dysplasia. Urinary calcium and/or magnesium also decreased in metastatic bone carcinoma and osteoporosis. Alkaline phosphatase did not change during the period of calcitonin treatment but was lowered in the posttreatment period in polyostotic fibrous dysplasia. Serum hydroxyproline showed a transient decrease in metastatic bone carcinoma.
Hypercalcemia of multiple myeloma and vitamin D intoxication was improved temporarily by calcitonin. These results suggest a beneficial effect of calcitonin in the treatment of some of the bone diseases and hypercalcemia.

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A mixture (DA-C) of dopamine hydrochloride and cholesterol in a ratio of 2 to 1 or 5 to 1 by weight was implanted into different hypothalamic regions of the rat and allowed to persist for more than two weeks. The estrous cycles and ovarian histology were examined to determine effects of the treatment. When the tip of the cannula containing DA-C (2 to 1) hit the posterior median eminence (ME) and a small part of the arcuate nucleus (AN), the rats showed prolonged estrus. The ovaries of these rats showed big follicles and no corpora lutea. When the tip of the cannula of DA-C (5 to 1) hit the posterior ME and a small part of the AN, the rats showed prolonged diestrus. The follicles and corpora lutea were small in the ovaries of these rats. Under our experimental conditions, DA seems to inhibit LH and FSH release at the level of the ME. When the tips of the cannulae containing DA-C were placed in AN, n. ventromedialis, n. premamillaris ventralis, n. premamillaris dorsalis, n. dorsomedialis pars ventralis or adenohypophysis, the rats showed cycles with or without minor irregularities.

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The responses of TSH, GH and insulin secretion to synthetic TRH were investigated in 6 normal subjects and 13 patients with endocrinopathies. Intramuscula injection of TRH in dose of 500 μg stimulated TSH secretion in normal individuals with the peak values of 8.0 to 20.0μU/ml at 20 or 40min after the injection. Three out of 4 patients with hyperthyroidism showed no response, the serum TSH level remaining undetectable up to 180min and one showed a minimal response at 40min. A patient who had been given orally a dose of 30mg per day of methimazole for 2weeks showed an exaggerated response, and a patient with chronic thyroiditis, who had a slightly elevated plasma TSH level at zero time, also showed a supernormal response as in cases of two acromegalics. No rise in plasma TSH occurred in a patient with hypopituitarism. All euthyroid patients with other endocrinopathies responded to synthetic TRH as in normal subjects. Plasma GH levels did not show any significant change up to 90 min, but later increased slightly during 120-180 min in the majority of cases. It may indicate that this increment is not a primary but a secondary effect of TRH or due to some stress-like factors. In acromegalic patients, a considerable rise in plasma GH level was observed to begin at 20min in response to TRH. In all cases, plasma insulin secretion did not change throughout the study.
It can be concluded that synthetic TRH is a useful tool for testing the pituitary reserve of TSH and for elucidating the pathophysiology of hypothalamo-pituitarythyroid axis.

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A method is presented for deriving a highly purified acid protease from calf thyroid. Thyroglobulin hydrolysis was very slow at pH 3.5 in comparison to hemoglobin hydrolysis. Protease was purified 285-fold from thyroid supernatant fraction by DEAE⁺Cellulose and Sephadex G-200 chromatography. The protein sedimented as a single component in the analytical centrifuge with a sedimentation constant of 3.6 S. Enzyme activity of the purified enzyme was increased by mercaptoethanol and cyste ne, and inhibited by n-chloromercuribenzoate.
A specific antibody against purifisd human-acid protease was produced in rabbits.
In the sera of patients with various thyroid diseases, antibody titers against acid protease were examined. No positive antibody titer was observed. The relation between the auto-immune disease in thyroid and antibody formation to acid protease is discussed.

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The inhibitory effect of porcine calcitonin on the development of immobilization osteoporosis was studied in rat through the analysis of calcium and collagen content of the femur and tibia and the measurement of cortical thickness of the femur. A marked decrease in the calcium content of the femur and collagen content of the tibia of the right hind limb immobilized through the application of a plaster cast was slightly but significantly inhibited by the simultaneous s.c. injection of either 50 MRCmU or 200 MRCmU of porcine calcitonin. However, calcitonin failed to show any effect against the decrease in the cortical thickness of the femur of the immobilized limbs of rats.
It is concluded that calcitonin diminishes the effect of immobilization on the development of osteoporosis possibly through the inhibition of bone resorption.

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The activity of an enzyme preferentially hydrolyzing parathyroid hormone in rat kidney homogenate was evaluated at various levels of parathyroid hormone activity and calcium metabolism. Transient hypercalcemia, hypocalcemia, increase and absence of parathyroid hormone for a short duration did not influence the enzyme activity. However, the enzyme activity showed a slight but significant decrease in parathyrordectomized rat in which sustained hypocalcemia was produced for 8 days. Hypercalcemia induced by the administration of dihydrotachysterol for 4 weeks provoked an increase in the enzyme activity.

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