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63 巻, 7 号
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ストレス負荷時のチロシン投与による効果について大川 とみ1987 年 63 巻 7 号 p. 823-835
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーThe environmental stress in the late gestational life has been reported to induce impairments of androgen-dependent sex differentiation of the rat brain. This study was performed to investigate the effects of prenatal stress on the features of gender role behavior and copulatory behavior which are masculinized by perinatal androgens. Further, a possible counteraction of tyrosine to the long-term effects of prenatal stress was examined, because the supplementation of amino-acid precursor of catecholamines during the stress is known to maintain the content of catecholamines in the brain, which is considered to contribute to the differentiation of the brain.
Time-mated pregnant females were subjected to the forced immobilization stress daily from day 15 of pregnancy to the day of delivery, and they received simultaneous i.p. injections of either tyrosine methylester HC1 (200mg/kg) or saline, less than 60 minutes before stress. Social play in the peripubescent period was observed in the male and female offspring. After maturation, they were castrated and male copulatory behavior under androgen-substitution was tested in the male offspring, and female copulatory behavior under estrogen-substitution was tested in the female offspring.
In the male offspring, prenatal stress caused a significant depletion of social play as well as male copulatory behavior, showing the demasculinization of gender role centers and mating centers. In the female offspring exposed to the prenatal stress, a significant increase of social play was observed. And their lordosis quotient did not alter, but a reduced attractivity against male partner was found. These results in the female offspring suggest some extent of masculinization occurred in both centers, probably due to the increase of androgens derived from the adrenal glands when stressed.
Tyrosine seemed to reduce the engagement of social play in both sexes, independently of the prenatal stress. On the other hand, tyrosine prevented, at least partially, the long-term effects of prenatal stress in copulatory behavior which were observed in this study. Tyrosine itself had no effect on copulatory behavior. The apparent counteraction of tyrosine in copulatory behavior suggests a positive involvement of catecholamines, especially norepinephrine, in the process of masculinization of the mating centers. The different action of tyrosine to these behaviors may reflect the fact that the different regions of the brain and separate mechanisms are responsible for the sexual differentiation of social play and copulatory behavior.抄録全体を表示PDF形式でダウンロード (1337K) -
重富 秀一, 上野 修一, 戸崎 英夫, 鴻野 浩, 佐藤 啓二, 森 一弥, 加藤 健, 田中 清宜, 芳賀 陽, 福地 総逸1987 年 63 巻 7 号 p. 836-845
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーWe evaluated the effects of dopamine (DA) and synthetic atrial natriuretic polypeptide (ANP) on the release of catecholamines (CA) from the adrenal medulla. Adrenal glands of male Wistar rats were superfused with Ringer's solution saturated with 95%, O2, 5% CO2 by the use of a continuous flow incubation system, and norepinephrine (NE) and epinephrine (E) concentrations in the perfusate were continuously measured by high pressure liquid chromatography with fluorescent reaction. And the effects of DA and ANP on the CA release were evaluated. Next the effects of metoclopramide (MC), dopamine (D2) antagonist, and glucagon were added in the Ringer's solution, and the changes of NE and E in the perfusate were determined.
Basal secretion of NE and E were 0.02-0.04ng/mg-wet weight/min and 0.05-0.1 ng/mg.wet weight/min, respectively. DA remarkably decreased both NE and E release, and the suppressive effect was dependent on DA concentration in the perfusate. MC clearly raised NE and E release as well as glucagon. The increasing effect of MC was perfectly suppressed by 10-4M of DA. But the effect of glucagon was not blocked by the same dose of DA. Alpha rANP (10-5M) slightly decreased the releases of NE and E from adrenal medulla, and the magnitude of the effect of rANP was smaller than that of DA. MC significantly increased NE and E release even when the adrenal gland was superfused with Ringer's solution containing 10-5 M of rANP.
These data suggest that the release of CA from adrenal medulla may be regulated by DA, and that the receptors specifically binding to DA may exist in adrenal medulla as well as sympathetic presynaps. We concluded that DA (but not ANP) may play an important role in controlling (suppressing) the activity of sympathoadrenomedullary system.抄録全体を表示PDF形式でダウンロード (825K) -
森 昌朋, 阿久沢 まさ子, 道又 敏夫, 山口 真史, 入内島 徳二, 小林 節雄1987 年 63 巻 7 号 p. 846-852
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーEffects of liquid protein diet (LPD), that is known to be poor in protein quality, on brain TRH and cyclo (His-Pro) concentrations were explored in young male rats. At day 23 of weaning, the animals were fed either a 20% casein diet ad libitum or a 20% LPD, or were pair-fed with a 20% casein diet. They were decapitated at day 35 or day 48. The body weight of those in the LPD group decreased significantly, and the loss was sustained in comparison with those in the pair-fed and ad libitum groups. The extrahypothalamic cyclo (His-Pro) concentrations were significantly greater in the LPD group than in the pair-fed and ad libitum groups throughout the experimental period, whereas these concentrations were similar in the pair-fed and ad libitum groups. At day 48, TRH concentrations in the hypothalamus and extrahypothalamus also increased in the LPD group in comparison with the concentrations in ad libitum group. These data indicate that quality of the protein component in the diet has a potential effect on alteration in the neuropeptides, TRH and cyclo (His-Pro), in the young rat brain.抄録全体を表示PDF形式でダウンロード (612K) -
合阪 幸三, 安藤 三郎, 國保 健太郎, 金田 幸枝, 多和田 哲雄, 吉田 浩介, 森 宏之1987 年 63 巻 7 号 p. 853-861
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーPresent study was performed to investigate whether TRH or metoclopramide (MCP) loading test was useful for the diagnosis of so-called occulted or latent hyperprolactinemia (transient increase of serum prolactin levels more than 30ng/ml during night; OHP).
The circadian profiles of serum prolactin levels were examined in 31 women (age : 23-32 years old) whose BBT charts showed biphasic patterns. Blood samplings had been done every two hours through an intravenous indwelling catheter without any disturbances. And seven cases of the OHP were selected. Five cases of the control were also selected at random. Then, LH-RH (100 μg) and TRH (500μg) loading test and LH-RH and MCP (10mg) loading test were performed to these cases in the mid-luteal phase of the same menstrual cycle at interval of two or three days, and serum FSH, LH and prolactin levels (at 0, 30, 60, 90,120 min. after the loading test) were determined by radioimmunoassay.
Serum prolactin levels in the OHP group showed significant higher levels than those of the control from 22 to 6 o'clock (p<0.05-0.005). By the administration of 500μg of TRH, serum prolactin levels of the OHP group increased significantly compared to those of the control at all sampling points (p<0.05-0.005), and also by the administration of 10 mg of MCP, the same result was obtained (p<0.05-0.02). The maximum peak of serum prolactin levels appeared at 30 min. after TRH or MCP loading. From these results, the diagnostic criteria for the OHP were decided tentatively as follows; serum prolactin levels more than 150 ng/ml at 30 min. after TRH loading or more than 250 ng/ml at 30 min. after MCP loading. Each value was approximated to the value of Mean - 1 S.D. in the OHP group which was obtained in this study. The usefulness of these criteria was examined in the patients with anovulatory cycles in the sterility clinic of our hospital and 24 cases of OHP by the TRH loading test (group A) and 19 cases of OHP by the MCP loading test (group B) were selected. Bromocriptine (5 mg/day) was administered for more than 30 days to these two groups and the effectiveness for the ovulation induction by the administration of bromocriptine was investigated for the confirmation whether the diagnostic criteria were appropriate.
The ovulations were induced in 18 cases of group A (75%) and 14 cases of group B (73.7%) by the administration of bromocriptine. There was no significant difference in the ratio of the ovulation induction between these two groups.
From these results, both TRH and MCP loading test were useful for the diagnosis of the OHP and the diagnostic criteria obtained in this study were appropriate for the diagnosis of the OHP.抄録全体を表示PDF形式でダウンロード (757K) -
中枢内aromatase活性の加令による変動及びaromataseの脳内分布について高橋 康男, 山中 英寿, 本間 誠次郎1987 年 63 巻 7 号 p. 862-869
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーSexual differentiation of brain structure and function is dependent on the hormonal environment during perinatal life. Recently, some studies have found the greatest aromatase activity in brain areas associated with sexual differentiation and sexual behavior, namely the hypothalamic and limbic structures. We have characterized the developmental and anatomical patterns of aromatase of aromatase activity in brains of fetal, neonatal, infantile and adult rats of both sexes. Aromatase activities in slices of brain were assayed by measuring the amount of 3H2 O formed during the conversion of [1β-3H] androstenedione to estrogen.
We have demonstrated major changes of the aromatase activity in the brain with age. Aromatase activities of both sexes reached peak values in the hypothalamus-preoptic area (HPOA) at least 3 days before birth. Thereafter, the activities declined to 3 weeks after birth.
We have found the greatest amount of aromatase activity in HPOA and amygdala of both sexes. Aromatase activities in HPOA and amygdala of neonatal male rat were higher than adult male rat. The hippocumpus, thalamus, pituitary, cerebral cortex and cerebellum all contained negligible aromatase activity. And, we studied HPOA in detail, aromatase activities in preoptic area and anterior part of hypothalamus were twice higher than that in posterior part of hypothalamus.
Aromatase activity reached peak values at the critical period of the sexual differentiation of the brain in HPOA and amygdala, associated with sexual behavior and sexual differentiation. We have reported that aromatase activity was regulated by androgen. We suggested that aromatization didn't occure effectively in female rat, owing to scarcity of androgen, which was activator and substrate of aromatase. Consequently, we considered that aromatase in the brain played an important role in the sexual differentiation of the brain for musculinization or defeminization at the critical period.抄録全体を表示PDF形式でダウンロード (867K) -
工藤 美穂子, 工藤 剛, 尾山 力1987 年 63 巻 7 号 p. 870-876
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーSeveral studies on the effects of atrial natriuretic polypeptide (ANP) on aldosterone production using isolated adrenal cells have been reported, and they have consistently demonstrated the reduced production of aldosterone by ANP. However, the results on the corticosterone production are sundry. Since ANP selectively activates particulate guanylate cyclase, a possibility could exist that cyclic GMP is the second messenger of ANP signal transduction. In order to demonstrate unequivocally a correlation of cyclic nucleotide levels with the ANP-induced steroidogenesis, we investigated the effects of various concentrations of a-human atrial natriuretic polypeptide (α-hANP) on aldosterone, corticosterone, cyclic AMP and cyclic GMP production in isolated glomerulosa and fasciculata cells of the rats.
Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male Wistar rats. The cell pellet was suspended in Hanks balanced salt solution 0.1% BSA buffer and distributed in 900μl aliquots to 12 × 75mm glass tubes. The samples were preincubated for 90 min. in a 37°C water bath under an atmosphere of 5% CO2 /95% O2. Aliquots of the test samples were added in a 100μl volume and incubated for 4hr. Total volume of the incubation mixture is 1.0ml. Aldosterone, cyclic AMP and cyclic GMP were measured by radioimmunoassay and corticosterone was determined by fluorimetric method.
The results indicated that α-hANP inhibited the secretion of aldosterone and corticosterone in rat glomerulosa cells.
α-hANP significantly decreased cyclic AMP production in the rat glomerulosa cells, while it markedly stimulated cyclic GMP production. On the other hand, α-hANP increased concentrations of cyclic GMP, but not of cyclic AMP, in a dose-dependent manner with an increase in corticosterone production in the rat fasciculata cells.
The role of cyclic GMP in steroidogenesis is controversial. Our findings suggest that cyclic GMP may play as the second messenger in α-hANP-induced steroidogenesis. Corticosterone production by α-hANP is a specific and intrinsic property of this peptide. In glomerulosa cell, corticosterone production was inhibited in spite of increased cyclic GMP production.
Thus corticosterone production by α-hANP may be dependent on concentration of cyclic GMP. Our speculation is supported firmly by a study that ANP directly stimulates the membrane guanylate cyclase.抄録全体を表示PDF形式でダウンロード (714K) -
森 昌朋, 入内島 徳二, 小林 節雄1987 年 63 巻 7 号 p. 877-883
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーIntraventricular administration of TRH and cyclo (His-Pro) has been investigated to cause the respectively, increase and decrease, in body temperature. We scrutinized whether cold exposure (4°C) may change TRH and cyclo (His-Pro) concentrations in the rat brain. While the blood TSH level rose after cold exposure, the rectal temperature was not significantly changed by the same exposure. Cyclo (His-Pro) concentrations in the hypothalamus increased significantly 15 and 30 min after cold exposure and returned to the basal level after 60 min. The extrahypothalamic concentrations of cyclo (His-Pro) decreased 60 min after cold exposure. No significant changes were observed in either the hypothalamic or extrahypothalamic concentrations of TRH under the cold status. It is postulated from the present data that the cold exposure-induced increase in cyclo (His-Pro) concentrations in the hypothalamus may be a potent hypothermic signal to elicit the counter regulatory mechanism (s) for the decrease in body temperature.抄録全体を表示PDF形式でダウンロード (561K) -
金 章〓, 森本 茂人, 福尾 恵介, 広中 隆志, 高 栄男, 白石 恒人, 大西 利夫, 熊原 雄一, 河井 百合子, 塩谷 弥兵衛, ...1987 年 63 巻 7 号 p. 884-893
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーCalcitonin gene-related peptide (CGRP) is a peptide recently found by recombinant DNA and molecular biological techniques in rat medullary thyroid carcinoma cells, but its physiological role (s) is unknown. We established a radioimmunoassay for this peptide using human-CGRP (1-37) as a standard, 125I-human-CGRP (1-37) as a tracer, and antirat-CGRP (28-37) serum as a first antibody. Aprotinin, an inhibitor of proteolytic enzymes in the plasma, was also added to the assay system, because in its absence the tracer was degraded during incubation with plasma samples. The sensitivity of the assay was 60 pg/ml and the intra- and inter-assay coefficients of variation were 6.0% and 8.5%, respectively. The recovery was 105±17%. The plasma levels of CGRP in 17 normal subjects (mean±S.D. age, 45±12 years) were all below 300 pg/ml, the mean level being 132±77 pg/ml. The levels were also below 300 pg/ml in 20 of 21 patients with medullary thyroid carcinoma, but one patient who had a high level of 942 pg/ml (mean value, 142±193 pg/ml). There was no significant difference between the mean plasma levels of CGRP in normal subjects and patients with medullary thyroid carcinoma. The mean plasma levels of CGRP in 5 pateints with medullary thyroid carcinoma did not increase in response to infusion of either 4.3 mg/kg of calcium in 10 minutes or 4 μg/kg of tetragastrin in 5 minutes, although the plasma levels of calcitonin in these patients increased markedly during these provocation tests. The levels of CGRP in the cerebrospinal fluid of 16 normal volunteers were all below the detectable limit (<60 pg/ml). These findings suggest that fewer patients with medullary thyroid carcinoma than reported previously have high plasma levels of CGRP, either in the basal state or in response to calcium or gastrin, and that the levels of CGRP in the cerebrospinal fluid of normal subjects are very low.抄録全体を表示PDF形式でダウンロード (802K) -
北脇 城1987 年 63 巻 7 号 p. 894-912
発行日: 1987/07/20
公開日: 2012/09/24
ジャーナル フリーKinetics of estradiol dehydrogenase (E2 DH) activity and the in vitro effects of progesterone (P) and synthetic steroids on E2 DH activity were investigated in human normal endometrium and endometrial carcinoma. In proliferative and secretory endometrium and endometrial carcinoma, E2 DH activities were 1.5±0.2, 10.1±1.1 and 1.2±0.1 nmol/mg protein/h (mean±SEM), Km was 2.3 μM, and Vmax were 0.20, 1.7 and 0.14 nmol/mg protein/10 min, respectively. Culturing proliferative endometria with progestogens resulted in a time- and dose-dependent stimulation of E2 DH activity up to 72 h and 10-6M, respectively. Medroxyprogesterone acetate had the highest effect to stimulate E2 DH activity among the steroids investigated. Chlormadinone acetate, norethindrone, P and R2323 were also effective. However, danazol, lynestrenol and E2 had negligible effect. Histological examination showed that progestogens caused early secretory change in the proliferative endometrium. These results indicate that the progestational activity is responsible for the elevation of E2 DH activity in proliferative endometrium and that the extent to which each steroid increases E2 DH activity may correlate with its local progestational activity. In the endometrial carcinoma, progestogens also stimulated E2 DH activity in seven cases out of nine during culture for 48h, but the elevation was lower than that in the proliferative endometrium.抄録全体を表示PDF形式でダウンロード (2410K)
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