Nineteen rats were obtained by the mating of two spontaneous diabetic males, that had diabetes for over one month, with three nondiabetic females, all of which were born from alloxan diabetic rats in the same successive generations. General observations on these animals and light and electron microscopic studies on their pancreatic islets as well as some other organs were performed. Among 19 rats, 11 developed diabetes spontaneously without any treatment, 5 of which showed long persistent diabetes.(a) Before the onset of diabetes, the pancreatic B-cells showed hypoplasia (reduced in number and size). Electron microscopically, some B-cells in the granular stage showed degranulation and an increased number of ribosomes, some B-cells in the predominantly agranular stage irregular dilatation of granular endoplasmic reticulum.(b) After the onset of diabetes, some pancreatic B-cells showed hydropic degeneration and vacuolar formation, other B-cells pyknosis and atrophy. Under electron microscopy, marked degranulation, swelling and vacuolation of mitochondria, and a decreased number of ribosomes were observed in all pancreatic B-cells, and in addition, marked irregular dilatation of granular endoplasmic reticulum in the predominantly agranular stage. The adrenal gland showed slight hypertrophy and in the cells of the fascicular zone an increased number of ribosomes and abundant dilated agranular endoplasmic reticula both before and after the onset of diabetes were observed. In the kidney, the glomerulus showed no obvious changes, but the renal tubules demonstrated deposition of glycogen particles in the diabetic stage and they did not show any degenerative lesions in their organelles.
In short, in experimental congenital diabetic rats, the pancreatic B-cells work excessively to maintain the animals free of diabetes, during the early prediabetic stage; however, with the aging process their growth disturbance becomes severe, they are exhausted and show degeneration and finally spontaneous diabetes occurs. The presumed hyperfunction of their adrenal cortex accelerates the onset of diabetes.

抄録全体を表示

When estradiol-17β dissolved in sesame oil was administered subcutaneously on the day of estrus in 4-day cyclic rats, spontaneous ovulation expected to occur on the next estrus was postponed for 3 days in maximum according to the dosage of estrogen injected. On the contrary, when estradiol was injected on the morning of diestrus I, ovulation occurred on the day of coming proestrus. This 1-day advancement of ovulation was demonstrated to be specific for estrogen, and it occurred only when a large amount of the steroid, 50μg per rat or more, was administered within a limited period of time on the morning of diestrus I, between 10:00 and 12:00 noon. The results indicate that estrogen as well as progesterone has a biphasic effect, either inhibitory or facilitatory, on the ovulating hormone release, although the effective period of time for estrogen during the estrous cycle is entirely different from that for progesterone, and it is emphasized that the advancement of ovulation can be induced by estrogen even in 4-day cyclic rats as well as in 5-day cyclers.

抄録全体を表示

A study was made to analyze the facilitatory effect of progesterone on ovulating hormone (OH) release in proestrous rats. Neural connections to the medial basal hypothalamus (MBH) or to the preoptic-suprachiasmatic (POA-SC) region of the hypothalamus were transected on the morning of proestrus with a curved knife or with an Lshaped knife. After the recovery from the surgical anesthesia, the rats were injected subcutaneously with progesterone, 1 mg per rat, and anesthetized again with pentobarbital during the time corresponding to the critical period for OH release in the intact rat. Facilitation by progesterone of OH release was confirmed in the next morning by counting the ova in the oviducts. Posterior deafferentation of the hypothalamus at the level of the mammillary body did not block the progesterone-induced ovulation. Anterior deaowqfferentation at the retrochiasmatic level completely blocked the ovulation. Progesterone-induced ovulation was also blocked by more rostral or broad dorsal deafferentation with a large curved or an L-shaped knife, the operation of which did not provide any damage on the structures of the POA-SC region. It is concluded that the facilitation of OH release by exogenous progesterone is due to the increase in the responsiveness of MH to the ovulatory stimulus coming from the higher CNS via the POA-SC region, rather than due to the direct stimulation of the hypothalamus to secrete releasing factor (s).

抄録全体を表示

When methylthiouracil (MTU) is injected chronically into hogs to block the iodination of thyroglobulin (TG), the iodine content decreased to essentially zero level after treatment with MTU for three or four weeks. One or two injections of thyroxine, given before killing the MTU-treated animals, caused a marked increase in the yield of noniodinated thyroglobulin. The treatment of animals with MTU also caused a significant decrease in the content of sialic acid residues of thyroglobulin. The sialic acid contents were as low as 0.8-0.9%(w/w%) in the poorly iodinated and non-iodinated thyroglobulins obtained from the MTU-treated animals, compared to a level of about 1.2%, as seen in normally iodinated thyroglobulin obtained from the untreated animals. This fact suggests that the differences (microheterogeneity) in the sialic acid content of the thyroglobulin preparations depend on a change in the regulating effect of thyrotrophin (TSH) action. The relathinship between the maturation of the thyroglobulin molecule and its sialic acid content is discussed.

抄録全体を表示

The rates of synthesis and release of GH, prolactin, and the whole protein in the anterior pituitary were measured by an in vitro method using mature male rats. The effect of starvation for 1, 3 and 5 days on these two distinct functions of the anterior pituitary is as follows: GH synthesis (per rat and per 100g body weight) decreases progressively. GH release (per rat) does not change much, but GH release (per 100g body weight) increases. The% release of GH, therefore, increases markedly. These changes in GH synthesis and release largely explain the earlier reports on alterations in pituitary content and plasma level of GH in starved rats. Prolactin synthesis and release (per rat) do not change following starvation. However, prolactin synthesis and release (per 100 g body weight) increase. The% release of prolactin does not change. Synthesis and release of the whole pituitary protein are decreased by starvation. Calculation suggested that pituitary proteins other than GH and prolactin are also influenced by starvation.

抄録全体を表示

When immunological measurement of a protein hormone is desired to be introduced into the clinical field, the antibody-antigen system has to be highly purified. The authors attempted to purify human placental lactogen (HPL) by combination of Sephadex gel filtration, DEAE-C chromatography and DEAE-Sephadex A-50, and succeeded in obtaining a highly purified HPL preparation which shows a single band on 7% polyacrylamide gel electrophoresis and is not contaminated with non-effective protein on immunoelectrophoresis. Anti-HPL-serum was made using this HPL, which showed no cross reaction with human serum protein.
Employing the above antigen-antibody system, the authors measured serum HPL of pregnant women at every stage of gestation by radioimmunoassay (RI). But, as a special apparatus and a complicated technique were needed for radioimmunoassay, Authors attempted to establish a clinically easier immunoassay of HPL by introducing single radial immunodifusion (SRI). The optimal conditions we finally decided for SRI are; antibody concentration, 1%; the thickness of the agar plate, 1.2mm; diameter of the well, 4mm; the amount of antigen placed, 10 μl. The regression coefficient was 5.48 and HPL over 5 μg was detectable. HPL values obtained by RI and SRI were almost identical. This SRI method made it much easier to measure serum HPL of pregnant women, and to observe pregnancy course from the view point of placental function. Furthermore, it may present an important clue in differential diagnosis between normal pregnancy and trophoblastic neoplasia by combination with measurement of human chorionic gonadotropin (HCG)

抄録全体を表示

Stereotaxic placement of bilateral electrolytic lesions in the anterior hypothalamus was carried out in adult female Wistar rats. Daily vaginal smears were taken from the 15th day after operation and those showing persistent vaginal estrus for more than 3 weeks were exposed to stress by making a croton oil pouch under the back skin. Sacrifices were performed 7 days later. If the medial preoptic area was destructed, rats exhibited persistent vaginal cornification and formed corpora lutea in their ovaries following exposure to stress, but when both the medial preoptic area and the suprachiasmatic nuclei were destroyed, animals likewise came into persistent estrus but failed to develop corpora lutea in their ovaries in response to similar stress. Following destruction of the lateral preoptic area, rats showed either persistent diestrus or vaginal estrous cycles. These findings suggest that the preoptic-suprachiasmatic region of the hypothalamus, especially the suprachiasmatic nuclei, is involved in luteinization of ovaries in persistent-estrous rats following exposure to stressful stimuli.

抄録全体を表示

1. Ovarian 20α-OH-P was determined at 5, 15, 30, 60min, 2, 5, 12, 24 hr and 2, 3, 4, 5, 7, 10 days after hypophysectomy in Wistar rats aged 7-8 weeks. Corticosterone in the adrenal was estimated in comparative study. Results indicated two distinct facts; one is that endogenous 20α-OH-P-genesis seems still lasting at least 4 days in the ovary after pituitary removal and, the other is that, in the adrenal gland, corticoidogenesis may immediately decline within 60min after the operation. That the most appropriate time after hypophysectomy must be 6 day when the ovary is no longer secreting significant quantity of ovarian steroid but when little sensitivity to gonadotropin appears to have been lost. In contrast, the appropriate time for ACTH bioassy is at least one hour after hypophysectomy. It is unlikely that pituitary support of ovarian steroidogenesis or function is essential. Additionaly, ovarian function was suppressed by the pentobarbital anesthesia.
2. FSH (NIH-S-3, 10μg/0.1ml saline, i. v.) or LH (NIH-S-10, 10μg/0.1ml saline, i. v.) or FSH (10μg) plus LH (10μg) was injected, without anesthesia to rats 6 days after hypophysectomy. They were decapitated without anesthesia at 5, 10, 30, 60, 120 and 180 min after the injection. Results showed that FSH alone can stimulate production of ovarian 20α-OH-P, significantly increasing the steroid content and concentration up to the level of intact animals as well as LH, and the combination of FSH plus LH likewise caused marked elevation of 20α-OH-P level. One type of synergism was manifested. In addition, ovarian response to exogenous pituitary gonadotropin (s) as evidenced by the 20α-OH-P level was very fast, taking place within 5 min. These results suggests that FSH, like LH, is indispensable for progestin biosynthesis in the rat ovary. Further discussion was made on the relationship between FSH and 20α-OH-P in the ovulatory process.

抄録全体を表示

Diurnal variations of CRF activity in the median eminence were observed not only in normal, but also in adrenalectomized and hypophysectomized male rats. The presence of circadian rhythm in CRF activity in the absence of the pituitary and adrenal gland suggests that the circadian rhythmicity of ACTH release is controlled by higher centers. The levels of CRF stores in hypophysectomized rats at any time of the day were markedly more increased than those in adrenalectomized and intact rats. This phenomenon suggests that CRF stores in the hypothalamus were inhibited by ACTH via short feedback mechanism. Furthermore, the peak of CRF stores in adrenalectomized and hypophysectomized rats showed a phase shift toward the earlier period of day. This finding may represent a shift of this rhythm secondary to the absences of the adrenal gland and the pituitary gland.

抄録全体を表示

Thirteen-day chick embryo shank skin was cultured for 4 days by the ‘Millipore’ filter-roller-tube method in a chemically defined medium, BGJb supplemented with ascorbate. Hydrocortisone was added into the medium at a concentration of 0.01μg/ml. The epidermis of control explants showing no sign of keratinization and that of hydrocortisone-treated explants covered with heavily cornified layers were examined for specific keratinous proteins (S-carboxymethyl epidermal proteins: SCMEp) with use of polyacrylamide disc electrophoresis.
SCMEp was prepared by treating the epidermis homogenate in 8 M urea first with 2-mercaptoethanol and secondly with monoiodoacetic acid. Supernatant of the reduced, carboxymethylated homogenate was electrophoresed with polyacrylamide gels containing 8 M urea in the presence or absence of sodium dodecyl sulfate.
When compared with the epidermis of embryonal and neonatal chicks in the normal course of development, SCMEp from control explants gave all the same electrophoretic pattern as that of younger embryos having no horny layer yet, whereas in some parts SCMEp from hydrocortisone-treated explants showed the highly advanced pattern as seen in older embryos and neonatal chicks.
These findings indicated that in the chick embryonic skin growing in vitro hydrocortisone selectively accelerated the synthesis of limited parts of the specific proteins to induce morphological keratinization of epidermal cells.

抄録全体を表示