Concerning the adrenocortical hormones and the aging process, especially in childhood and adolescence, the results by age level of the studies by the author and coworkers on the following items are summarized : 1) Plasma levels of cortisol and corticosterone, 2) Plasma transcortin binding of C-14 cortisol (% bound) and erythrocyte C-14 cortisol uptake, 3) Plasma cortisol levels after ACTH stimulation and also the values in patients immediately after death, 4) Certain important urinary metabolites of cortisol, 5) Urinary excretion of tetrahydroaldosterone, 6) Urinary excretion of 17-KS fractions.
The level of cortisol in the plasma was slightly low during the newborn period, however transcortin binding of C-14 cortisol (% bound) was also low in newborns and young infants and cortisol value in the plasma after ACTH stimulation or immediately after death increased more markedly, showing higher values in young infants than in older children. Urinary metabolites of cortisol also showed age-specifity more markedly after ACTH stimulation. Even in young infants, urinary aldosterone excretion was increased after Narestriction in most of the cases examined. The production of adrenal androgens increased sharply before puberty and a close relationship was observed between the urinary excretion of 11-deoxy 17-KS fractions and the growth spurt during the adolescence period.
These results showed that the secretion and metabolic pathways of the adrenocortical hormones of the children are different from those of the adult and even in the children they are not the same during each period of childhood. We would like to emphasize that some of these differences due to age becomes more marked under conditions when the adrenal glands become stimulated.
To study the alternation of functions of adrenal cortex and adrenal medulla and the relationship between them in aged persons, plasma levels of cortisol and corticosterone, urinary excretion of 17-ketogenic steroid fractions, pregnanediol (P-diol), pregnanetriol (P-triol), catecholamines (CA), total metanephrine (TMN) and VMA were measured by J.v.d. Vies', modified Morris', Klopper's, modified Stern-Few's, modified Eular-Lis-hajko's, Pisano's and Sandler's method respectively. Hormones and thier metabolites above mentioned in young and adult subjects also were measured as a control. Both groups of examined persons were healthy. The plasma levels of cortisol and corticosterone were within the range of the control. Daily urinary excretions of 17-ketogenic sterioid (17-KGS), 11-oxygenated 17-KGS (11-oxy 17-KGS), 11 -deoxy 17-KGS, P-triol and P-diol decreased in the aged but the ratio of 11-deoxy 17-KGS to 11-oxy 17-KGS elevated in over 8th decade. Following the intramuscular administration of ACTH-Z, the increase of 17-KGS, 11-oxy 17-KGS, P-diol and P-triol in the aged was less than in the control, but that of 11-deoxy 17-KGS was as much as that of the control. Therefore, the ratio of 11-deoxy 17-KGS to 11-oxy 17-KGS elevated in the aged. In the aged, the increase of 11-deoxy 17-KGS following the oral administration of SU-4885 was greater than that in the control, consequently showing a remarkable elevation of the ratio of 11-deoxy 17-KGS to 11-oxy 17-KGS. These results from both ACTH-Z test and SU-4885 test suggested that there was some disturbance of cortisol synthesis in adrenal cortex in the aged.
In the aged, daily urinary excretions of noradrenaline (NA) and TMA increased more than in the control. The control showed significant difference as to sex, but the aged did not. Daily urinary excretion of adrenaline (A) in the aged showed large variation, but the mean value was within the range of the control. Urinary excretion of VMA in the aged was also within the range of the control. In the aged, the ratio of A to NA was lower, and that of TMN to VMA was higher than in the control, but that of CA to TMA was within the range of the control. In both aged and young subjects,

抄録全体を表示

To elucidate the aging process of male reproductive function, testis and ventral prostate from rats of various ages as well as response of the latter tissue to the administered testosterone were examined biochemically.
The weight of testis reached to a constant maximum level by 14th week after birth and no significant change was observed hereafter. However, accessory sex organs gained weight further and reached to a maximum level at 10 weeks later, then the tissue tended to gradural involvement with age. According to these observations, rats of more than one year-old were referred to as the “aged” in this experiment. Contents of RNA and DNA in testis showed decreasing tendency with age after maturation, while the tissue contents of protein and water did not exhibit any significant changes in rats of various ages examined. The tissue concentration of ascorbic acid also decreased slightly along the time after maturation. Among the enzymes examined, activities of LDH, MDH and ICDH in the soluble fraction and acid, alkaline phosphatases and β-glucuronidase in the homogenate in aged testes were not different significantly from those of young or adult ones. Although an impairment of sperm formation was reveald morphologically, the activity of DNA-polymerase was not impaired significantly. A most conspicuous difference between young or adult and aged testes in the biochemical parameters examined was found in the activity of testosterone formation in vitro from progesterone as the substrate. In this instance, only 1/3 of the activity was detected in testes from aged animals. An examination of the activity of protein biosynthesis in the tissue assessed by the rate of radioactive phenylalanine incorporation revealed only a slight difference between rats of various ages.
In ventral prostate, the ratio of RNA to DNA contents showed progressive decrease with age. In addition, a marked decrease in tissue citrate content from aged animals was noticed. An interesting feature was observed in the activity changes of acid and alkaline phosphatase, activity of the former enzyme did not exhibit any changes throughout the experimental period, while the latter enzyme showed a tendency of abrupt increase in the animals of more than one year-old. ATPase activity was remained constant, however, RNA-polymerase in nucleus was slightly decreased irrespective of ionic strength of the incubation medium used for the activity determination in aged tissues. It was quite impressive that steroid 5α-reductase and 17β-dehydrogenase, both participate in the testosterone metabolism behaved differently with age, the former decreased to the half level in aged tissues but the latter did not differed significantly. The degree of response of castrated, aged rats to the externally administered testosterone was also determined. The weight and content of RNA in ventral prostate of animals of various ages responded in almost same pattern to the administered testosterone, however, the degree of the increase in DNA-polymerase activity and in DNA content was diminished significantly in aged tissues.
In the human male, the sexual potency decrease characteristically in castrates and hypogonadotropic eunuchoidisms. Those sexual potency can be controlled with androgenic hormone successfully, in addition those masculine structure to normal condition altogether. Thus, we believe that the androgenic hormone is effective to regain the sexual potency.
In aging males, many investigators suggest, that the secretion of androgenic hormone may decrease at the slow rate. In our many clinical experiences on the therapy of the psychic impotence in aging males, we get some androgenic hormones in our therapeutic programs ordinarily. Those effect is most remarkable as a “trigger”, that may can improve those sexual pattern.

抄録全体を表示

It is recognized statistically and clinically that the lowering of female fertility appears with age. During the climacteric, there is frequent to happen ovarian dysfunction, such as menstrual disorders or dysfunctional uterine bleeding, and the climacteric symptoms as somatic and psychic changes. These clinical changes suggest the lowering of ovarian function according to aging. However, from the aspects of urinary estrogen level, the strinkig decrease of the level is not observed before menopause. In postmenopausal women, it is low value, as general, but the higher levels are revealed in some cases. In any event, very low level as in childhood is not observed.
From the recording of 18,213 menstrual cycles, it is observed that the length of cycle shortens with age. Basal temperature records of 3,000 ovulatory cycles shows that the average length of follicular phase shortens with age, although that of luteal phase does not change in women of over 20 years old. So it is clear that the shortening of menstrual cycle is a result of shortening of follicular phase. The shortening of period and decrease of flow are also observed in women of over 35 years old, and the increase of inadequate luteal phase or anovulatory cycle especially in women of over 40 years old.
Lowering of ovarian function with age does not mean only the decrease of estrogen secretion, but irregularity of ovarian cycle function that induces umblance of estrogen and progesterone secretion. The fact that the endometrial hyperplasia induced by prolonged or profuse estrogen action frequently takes place in climacteric women supports the abovementioned opinion.
Urinary total gonadotrophins increase in some cases of menopausal women, and rise remarkably in postmenopausal women. Follicle stimulating hormone is within normal value or a little higher before menopause, and rises usually in postmenopausal women. Then, in more than five years after menopause, FSH tends to return to normal range. LH increases to ovulatory level in postmenopausal women. Urinary 17KS value increases during menopause.
With age, ovarian size becomes smaller, and following histological changes appear : appearance of germinal inclusion cyst or corpus albicans cyst, disappearance of corpus luteum, decrease of atretic follicle, disappearance of graafian follicle, decrease of a number of a internal theca cell and interstitial cell, accumulation of Sudan IV strain in ovarian cortex, and increase of Sudan IV strain in wand of ovarian vessels. From these phenomenon, it is supposed that structual ovarian atrophy begins between 35 and 40 years old. Especially blood vessels in ovary change remarkably after 35 years old. So, the change of ovarian vessel is suggested to play an important role to lowering of ovarian function.

抄録全体を表示

Thyroid seems to undergo gradual lowering of it's function along with the advance of age parallel with the lowering of cellular metabolism, but under reservation of potent capacity to react upon TSH for long time. Significant increase of TBG capacity in old age seems to be playing a role as a buffer system against over normal increase of thyroid hormone in blood. Furthermore a distinct impairment of feedback mechanism between thyroid and hypothalamo-pituitary system was demonstrated in old people. As a cause of this impairment possible decrease of cerebral circulating blood volume, basing upon cerebral arteriosclerosis, was postulated. Hypothyroidism seems to promote the pathological aging and this corresponds to the clinical impression of hypothyroid patients showing frequently far more advanced age than real age. But from the standpoint of life expectancy mild hypothyroidism seems to be advantageous for long life. The last postulation is supported by the relatively mild lowering of thyroid function, corresponding to the lowered metabolism of the tissue, in old people.
Until the 5th day after birth in the neonatal period, ¹³¹I-thyroidal uptake, serum T₄, ¹³¹I-T₃ resin uptake, and free T₄ index are high, definitely indicating the state of physiological hyperactivity of the thyroid.
In the course of development from the infantile to adult period, none of these 4 parameters showed significant variations. However, plasma inorganic iodine is lower and renal iodide clearance and thyroidal iodide clearance is higher as the age of the subject is younger, indicating more active iodine metabolism in younger age.
Since iodine uptake is abundant in each age group, no possibility of deficiency is expected. With regard to T₄ metabolism, both T₄ turnover rate and T₄ degradation rate was higher in younger age. TBG and TBPA also varied according to age. Male to female difference was seen after adolescence probably due to the influence of sex hormone. Based on these results, the physiological goiter frequently seen in adolescent females is probably not due to the increase in the requirement of thyroid hormone, iodine deficiency, and increase of renal iodide clearance but is apparently under the influence of estrogens.

抄録全体を表示

正常人にMethimazole 10mg 3日間投与の前処置をして甲状腺に軽度の有機化障碍を作ってKClO₄試験を行なった。前処置によって生じた障碍はヨード制限食下でのKClO₄試験で¹³¹I放出がみられず, 無機ヨード0.5mgを¹³¹Itracerと共に投与したKClO₄試験で放出がみられた.臨床的に, 甲状腺の軽度の有機化障碍の検出に有用であり, あるいはヨードに過敏に反応し抑制効果が生じる甲状腺腫の検出に有用な手段として提唱する.

抄録全体を表示

Glycolysis の律速酵素中, その調節機構上重要な位置を占めている phosphofructokinase : PFK活性の動態をヒト, ラット子宮について検索を行なつた.Estrogenを去勢ラットに投与すると, その子宮PFK活性は24時間で増加し, 5日間連続投与により明らかな増加を示した.Progesterone 同時投与によりその活性誘導の抑制は認められなかつた.
ヒト, ラット子宮筋のPFK活性は妊娠末期に著増した.これは内因性estrogen, progestogenによるもので, 子宮における生物学的エネルギー産生特に分娩時に寄与しているものと考えられる.

抄録全体を表示

正常人における甲状腺I¹³¹クリアランスを¹³¹I注射後120分まで経時的に追求したところ, 4分以降著しい低下を認めた.この現象の分析から, 甲状腺摂取ヨードプールよりのヨード流出を証明した.このヨード流出のヨード流入に対する割合は, 血漿無機ヨード濃度に有意の相関を示し, ヨード環境の変化に対する甲状腺自己調節機構として働いていることを示した.

抄録全体を表示

雄性白鼠の肝mitochondriaを分離し, magnetic stirrerを使用して30分間室温でincubationするとmitochondriaのoxidative phosphorylationは明白に低下した.100m U/mlのpork insulin;2μmolesのGSSGのinvitroの添加は低下を有意に抑制したが, 2μmolesのGSHは低下を抑制しなかつた.インスリンは肝mitochondriaのagingに対してinvitroで保護作用を有することが判明したが, かかるインスリン作用には-S-S-の関与が想像された.このインスリン作用と肝との関連について2, 3の考察を行なつた.

抄録全体を表示

ニワトリヨード甲状腺腫を中心として, thyroglobulin水解活性に対する大量ヨードの影響をpH3.6でのautohydrolysisを用いpaperchromatographyの放射能から測定検討した.トリに1 mgの無機ヨード4週間投与によりり発生した甲状腺腫の水解能は低下を示したが, 類似の低下は, トリ, ラットに無機ヨードをsingle injecdonした後にも見られ, 一般にヨード投与後, 腺内に増加したホルモンの血中への分泌を調節する機転によるものと想定する.

抄録全体を表示

バセドウ病患者血中に, 特異的に認められるLATSは, 抗体類似の性質を有し, 本症病因との関連で注目を集めている.然しその産生部位や, 抗原が明らかでなく, その本態は依然不明である.そこでLATS活性が高値を示すバセドウ病患者末梢淋巴球を分離, PHAを添加培養する事で, in vitroでLATS活性の産生を認め, 本活性が非特異的反応でない事, 又種々の点で現在明らかにされている血中LATSの性質を総て具備している事, を示しLATSが抗体産生細胞でつくられうる事を明らかにした.

抄録全体を表示

アロキサン糖尿病白鼠肝のTBA値は対照白鼠肝より明らかに高かつた.インスリン治療のアロキサン糖尿病白鼠肝では, TBA値の上昇はなかつた.In vitroのインスリン添加で, 対照白鼠肝TBA値は低下したが, アロキサン糖尿病白鼠肝では低下が明らかでなかつた.
In vitroのVE, albuminの添加で, 対照群肝のTBAの低下は明白に認められたが, アロキサン糖尿病肝ではTBA値の低下は対照群ほどではなかつた.以上の成績に基づき, インスリンと過酸化脂質に関して2, 3の考察を行なつた.

抄録全体を表示

カイウサギにEDTA (体重kg当り25mg) を投与し, 血中カルシウムならびに上皮小体主細胞の微細構造の変化を観察した.その結果, 血中カルシウム値はEDTA投与後急速に低下し, 約5分後に最低値に達し, その後徐々に上昇してEDTA投与45分ないし60分後には投与前の値に戻る.一方, 上皮小体主細胞においては, EDTA投与30秒後には, すでに分泌顆粒の放出は開始されており, 5分後には殆んど総て放出されてしまう.以後, 分泌穎粒の放出は行なわれずに, 新しい分泌顆粒の形成が盛んとなり, EDTA投与30分後には, すでに新しく成熟した分泌顆粒がみられる.そして, 投与90分後に至ると, 大部分の主細胞は, EDTA投与前の, いわゆる静止期の微細構造を呈するようになる.

抄録全体を表示