下垂体ホルモンであるACTHとMSHは互いにその構造が以ており, ためにACTHは弱いながらMSH作用があり, またMSHにはわずかではあるがACTH作用がある.そのため従来広く用いられていた生物学的測定法ではこの両者を完全に分離測定することは困難であつた.清水らはAddison病, Cushing病で両側の副腎摘除をうけた症例などについて検討を加え, これらの患者血中にはACTH以外にMsH作用を有する物質が増加していることを証明しているが, (J.clin.Endocr., 25 : 984, 1965) しかしこれが何であるかは明らかにされていない.
私はアメリカVanderbilt大学に5年間滞在中, Liddle教授の下で, α-MSHとβ-MSHのradioimmunoassayを確立し, これにACTHとMSHの生物学的測定を加えることにより, ACTHとMSHの相互関係につき検討したので, ここで得られた成績につき述べてみたい.

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The effect of neurohypophyseal hormones on the peripheral action of catecholamines was investigated in two different way of experiments. First, the isolated smooth muscle was used to examine the effect of neurohypophyseal hormones on the action of catecholamines. In this experiment, oxytocin and its analogue were found to inhibit the contractile response of rabbit aorta strips caused by norepinephrine, however, Lys-vasopressin and its analogue had almost no effect on the action of norepinephrine. Oxytocin was also found to inhibit the relaxation of guinea-pig tracheal strips caused by epinephrine. The inhibitory effect of oxytocin was thought to be specific for the action of catecholamines, because this hormone did not show any effect on the action of angiotensin, histamine and acetylcholine. Next experiment was designed to see the effect of neurohypophyseal hormones on plasma FFA in the rat which was pretreated with reserpine or adrenergic blocking agents. In the normal rat, the decrease of plasma FFA was found after LVP treatment, but almost no change after oxytocin treatment. Although pretreatment of phenoxybenzamine did not inhibit the effect of LVP, propranolol did inhibit the effect of LVP on plasma FFA. In reserpinized rats, the increase of plasma FFA was found after LVP treatment, and this result suggested the catecholamine-like action of LVP under the condition in which catecholamines in the tissue were depleted.

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副甲状腺ホルモン (以下PTHと略す) とカルチトニン (以下CTと略す) が血清Caの調節, 骨代謝において重要な役割を演じている事は周知の事実で副甲状腺ホルモンが血清Caを上昇させるのに対しカルチトニンは逆にこれを低下させる作用を有する事からこれら二つのホルモンの相互作用が古くから注目されている.さてこれら二つのホルモンの相互関係を論ずるに当りまず第一に分泌調節, 第二に血清Caの調節・第三に骨における相互作用につき我々の最近の知見につき報告したい.

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In order to elucidate the mechanism of the interrelation between actions of parathyroid hormone and calcitonin both in vivo and in vitro experiments were performed.
1. Parathyroid hormone was shown to counteract the action of calcitonin which enhanced lowering serum calcium in thyroparathyroidectomized rats.
2. Although parathyroid hormone never changed the serum calcium level in vitamin D deficient rats, it countera ctedcalcitonin which lowered the serum calcium level in vitamin D deficient rats.
3. It was demonstrated wthat when bone chips from the distal part of femur and thyroparathyroid complex, parathyroid extirpated thyroids, or parathyroids from the same or another animal were incubated simultaneously in Krebs Ringer bicarbonate solution, modified BGJb-HW2 medium or serum under the atmosphere of 95% O₂ and 5% CO₂, such a system reflected the functions of parathyroids and/or thyroidsunder respective conditions. It was shown that although parathyroid counteracted the effect of thyroids which lowered the level of media calcium, parathyroids did not for themselves raise the medium calcium in 2 hours of incubation. However, when the medium calcium level was low and the incubation was continued until 4 hours in mature rats, the parathyroids raised the medium calcium higher than the thyroparathyroid complex did. When parathyroidectomy (PTX) was performed 22 hours before the incubation, the medium in which only bones were incubated showed lower level of calcium in 2 hours of incubation than controls. When PTX was performed 19 hours before and a dose of 100 UPS u. of parathyroid extract was given 5 hours before the incubation, the medium showed higher level of calcium in 4 hours of the incubation than PTX controls. From these experiments it was shown that parathyroids showed 2 ways of action on bone-first via the direct counteracting effect on calcitonin and secondly via the direct effect on bone.

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Antagonism between parathyroid hormone (PTH) and glucocorticoids was demonstrated in the following studies.
1) The steroid therapeutic test was performed in 11 patients with primary hyperparathyroidism and also in 6 patients with hypoparathyroidism that had foods containing 500 mg of calcium and 1000 mg of phosphorus a day. The administration of prednisolone 40 mg/day caused retention of phosphorus, hypocalcemia and tetany in all patients with hypoparathyroidism while did not reveal significant changes in the concentrations of serum calcium and phosphorus in patients with primary hyperparathyroidism. No effect of prednisolone was demonstrated in the concentrations of serum calcium and phosphorus in normal subjects.
2) Clearance studies were performed in intact and parathyroidectomized (PTX) dogs and the tubular reabsorption of phosphorus (TRP) was calculated in every 15 minutes. In 3 intact and 3 PTX dogs, %TRP was decreased gradually and showed minimal 75 to 90 minutes after the administration of 200 units of PTH. Infusion of 20 mg of prednisolone for 3 hours, however, demonstrated a marked prevention of a decrease of %TRP induced by PTH 200 units.
3) Disappearance of ¹²⁵I-PTH from serum was studied in intact dogs and it was demonstrated that infusion of prednisolone 40 mg for 3 hours induced an increase of the turnover rate of ¹²⁵I-PTH with an elevation of the urinary excretion rate of ¹²⁵I.

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Insulin分泌刺戟としてブドー糖が第一義的役割を演じていることは種々の成績より明らかであるが, それ以外にもinsulin分泌に関与する多くの物質が知られている.これら個々の物質のinsulin分泌能にっいては比較的よく研究されているが, 生体内でこれら諸物質がinsulin分泌に対し生理的に如何なる役割を演じているかはなお明らかでない.
消化管と糖代謝との関係は古くより注目されていた課題であつたが, 最近Mclntyreらが経口的にブドー糖を投与した際等量のブドー糖の静脈内負荷に比し血中insulin反応が大であるという成績を示し, 或いはDupréらがsecretinが静脈内に投与されたブドー糖の同化を促進するという事実を明らかにしてより, 一時期関心の薄れていた消化管と糖代謝の問題が再び注目をあびるに到つた.
著者らは91ucagonの有するinsulin分泌刺戟能の機序を解明し, 更に消化管由来91ucagon様物質の血中動態より, insulin分泌に及ぼす消化管の意義についての解明を試みた.

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An investigation was made into the interaction between insulin and glucagon in the lipolysis of adipose tissue, by an in vitro experiment using epididymal adipose tissue of the rat.
The lipolytic action of glucagon in a low concentration of 0.1 μg/ml was completely inhibited by the addition of 100 μU/ml of insulin, however, the lipolytic action of glucagon in a high concentration, such as 10 μg/ml, was not only uninhibited but in some instances even promoted, by the addition of insulin. Adipose tissue was pre-incubated in a medium containing 10 μg/ml glucagon, and insulin was added subsequently, however, lipolysis was not inhibited. The promotion of lipolysis of adipose tissue by the addition of dibutyryl cyclic-AMP in a concentration of 1000 μg/ml was not inhibited by the addition of insulin. On the other hand, the increased lipolysis due to the addition of theophylline was completely inhibited by the addition of insulin.
From the foregoing, it may be said that glucagon promotes the action of adenyl cyclase, whereas insulin inhibits it, and consequently, there is a possibility for the strong lipolytic action of a high concentration of glucagon to be uninhibited by insulin.

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Though the work of Wurtman & Axelrod (1965, 1966) on the effect of dexamethasone and hypophysectomy on the activity of PNMT in the rat adrenal, that corticosterone (CS) induces the formation of PNMT seems to be widely accepted, it remains a few unsettled problems. Results obtained were as follows;
1) In report on the effect of immobilization (immobil.) upon adrenal cortex and medulla of the rat (Okamoto, 1970), his conclusion was that the procedure of immobil. resulted in a marked increase of the activity of these both tissues as reflected in a persistent elevation of plasma CS and a significant decrease of adrenal catecholamines (CA) followed by a overcompensated period due to the increased CA synthesis. In contrast with the sham-operated rat, no remarkable change of adrenal CA was observed in the coeliac ganglionectomized rat during or on the period of setting free from immobilization.
The results are interpreted to indicate that the effect of immobil. on adrenal CA is mediated by an elevated sympathetic activity and succeeded by the increased CA synthesis as the result of the decreased endproduct inhibition.
2) The single administration of such adrenocortical blockers as dexamethasone, 3-methylcholantrane, 7, 12-dimethylbenz (α) anthracene (DMBA) and metopyrone did not induce a significant change of suprarenal adrenaline (AD) content except for relatively decreased AD content in hypophysectomized rats. When the procedure of immobil. was added to the rats pretreated with these adrenocortical blockers, the repletions of suprarenal AD which is expected to occur after setting free from immobil., were remarkedly suppressed in all groups which were administered with such drugs as well as in the hypophysectomized rats. These findings indicate that Wurtman & Axelrod's theory is almost valid in the adrenal gland of the non-hypophysectomized rat which was acutely inhibited by several adrenocortical blockers.
3) But the tendency of the repletion of suprarenal AD content was still observed after the restraint of the rat which was pretreated with any tested adrenocortical blocker as well as of the hypophysectomized rat. It is logical to assume that the methylation of NA in the adrenal medulla may be kept in reserve, even if the aboundant supply of CS from the adrenal cortex to the medulla is acutely interrupted.
4) In spite of such intensive stimulus as producing a marked elevation of plasma CS, the effect of the immobil. on suprarenal AD content of the rat pretreated with DMBA, was diminished with coeliac ganglionectomy. These facts suggest that further stimulation of adrenocortical output does not increase AD synthesis.
5) The histological analysis of “adrenocorticlolysis” due to the treatment with DMBA revealed the massive destruction of the sinusoid in the rat adrenal cortex which is assumed to supply a high concentration of CS from the cortex to the medulla. From these results, it is necessary for the methylation of NA on the adrenal medulla that there is not any circulatory disturbance from the adrenal cortex to the adrenal medulla.
6) The decreased rate of the suprarenal AD content due to CA synthesis blocker was more accelerated in the DMBA pre-treated rats than in the non-treated rats. But no significant difference between the dexamethasone (20 γ/rat/day) pretreated rats and the non-treated rats was observed as concerned with the decreased rate of the suprarenal AD content due to CA synthesis blocker.
7) The prodceure of the immobilization which is able to activate intensively both the adrenal cortex and medulla is a useful tool for the study of the intimate correlation between the adrenal cortex and the adrenal medulla.

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Summarizing the results obtained from our experiments, ovulatory release of LH with a peak around 7 p.m. of proestrus depends on the foregoing increase in estrogen secretion starting in the afternoon of diestrus II, and a certain amount of estrogen secreted during. the period from 4 a.m. to 7 a.m. of proestrus is definitely essential for occurrence of LH release under our breeding conditions. Estrogen secretion from the ovary with mature follicles is completely under the control of the pituitary, and it is not automatically derived from the secretory function of developing tollicles bui sustained and stimulated by both LH and FSH. A drastic fall of ovarian estrogen secretion immediately after the maximal elevation of plasma LH is not due to the deficiency of pituitary factor, which is responsible for estrogen secretion, but due to the depletion of ovarian reactivity to the factor.
Preovulatory increase in progesterone secretion is entirely under the control of the pituitary and it is the result of LH release. However, a mild increase in progesterone secretion at diestrus I is not dependent on the pituitary function but it is a reflection of the function of developing corpora lutea which automatically secret progesterone and 20α-hydroxypregn-4-en-3-one.
Expected ovulation is delayed by progesterone administered during late diestrous stage. Estrogen given in the estrous morning prolongs the increased secretion of progesterone in the luteal phase to produce delayed ovulation. Exogenous estrogen given at an appropriate time induces ovulation in a transient anovulatory state caused by progesterone. Progesterone also facilitates ovulation in the progesterone-induced anovulatory state when the second progesterone is administered at a critical time (1 to 5 p.m.) on the third day following the first day of the initial progesterone treatment. These alterations in ovulation time caused by exogenous steroids are not an hourly regulation but a daily one. However, a few hour advancement of preovulatory increase in progesterone secretion and of ovulation can be induced by a single subcutaneous injection of progesterone given on the morning of proestrus (around 11 a.m.). The site of action of progesterone facilitating ovulatory release of LH is in the median eminence-arcuate region of hypothalamus.
From these findings a causal relationship between ovulatory release of LH and ovarian steroid secretion in our 4-day cyclic rats may be explained as follows. Progesterone withdrawal in accordance with the degeneration of corpora lutea removes the suppression to gonadotropin secretion, and thus results in the increase of estrogen secretion. A certain level of circulating estrogen activates the neural mechanism concerning LH release. This estrogen activation is completed by the time 12 hrs. prior to the critical time of LH release for occurrence of ovulation. The activated neural mechanism for LH release is put into action only at the critical time which is fixed at 5 to 7 p.m. by our illuminating schedule of 12 hrs. light from 8 a.m. to 8 p.m. An initial part of the released LH stimulated the secretion of progesterone, which, in turn, facilitates further release of LH probably by lowering the threshold of neural process to drive at LH release. LH promotes cell differentiation of the follicles which results in a rapid depression of estrogen secreting ability of the ovary. Increased amount of circulating progesterone suppresses the secretion of LH probably by acting on the neural process. After ovulation, newly formed corpora lutea secret progesterone, which inhibits the secretion of gonadotropin, and thus keeps the estrogen secretion low during estrous and early diestrous phase.

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Patterns of urinary FSH and LH during the menstrual cycle have not been established, much less those of anovulatory women. We have investigated the effects of various ovulatory agents on urinary hormone excretion.
Urinary FSH of 77 anovulatory patients before treatment was determined by IgarashiMcCann' method and LH by OAAD method and radioimmunoassay.
Most of the patients with amenorrhea second grade showed hyper-FSH or hypo-FSH, and urinary FSH values of other anovulatory types were almost in normal range. The urinary LH values indicated the same tendency as FSH.
Urinary FSH of 30 anovulatory women treated with clomid almost increased after administration, regardless of ovulation. The urinary LH of those increased only in ovulated cases. Therefore, we agree with Jacobson et al. who reported the simultaneous increases of both plasma FSH and LH with clomid treatment, employing radioimmunoassay.
Urinary FSH and LH were also measured in 9 ovulated arid 14 failed cases of anovulatory patients during sexovid (F6066) therapy. FSH levels rose in all cases ovulated during or immediately following sexovid therapies. While, in six cases of fourteen, increased FSH excretion was noted in the absence of ovulation, later than the 20th day of administration. So it was postulated in failed cases that late rises in FSH levels could not sufficiently develop the follicles ready for ovulation, even if LH were simultaneously released. The significant LH peaks occured approximately on day of ovulation in all ovulatory cycles induced with sexovid, but LH levels were elevated in only four cases out of failed fourteen cases.
From the results above described, I believe that timely releases of FSH and then LH with such mode as reported by Fukushima et al. and recently by Stevens, might be indispensable for ovulation, even if it were induced.

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Patterns of urinary FSH and LH during the menstrual cycle have not been established, much less those of anovulatory women. We have investigated the effects of various ovulatory agents on urinary hormone excretion.
Urinary FSH of 77 anovulatory patients before treatment was determined by IgarashiMcCann' method and LH by OAAD method and radioimmunoassay.
Most of the patients with amenorrhea second grade showed hyper-FSH or hypo-FSH, and urinary FSH values of other anovulatory types were almost in normal range. The urinary LH values indicated the same tendency as FSH.
Urinary FSH of 30 anovulatory women treated with clomid almost increased after administration, regardless of ovulation. The urinary LH of those increased only in ovulated cases. Therefore, we agree with Jacobson et al. who reported the simultaneous increases of both plasma FSH and LH with clomid treatment, employing radioimmunoassay.
Urinary FSH and LH were also measured in 9 ovulated arid 14 failed cases of anovulatory patients during sexovid (F6066) therapy. FSH levels rose in all cases ovulated during or immediately following sexovid therapies. While, in six cases of fourteen, increased FSH excretion was noted in the absence of ovulation, later than the 20th day of administration. So it was postulated in failed cases that late rises in FSH levels could not sufficiently develop the follicles ready for ovulation, even if LH were simultaneously released. The significant LH peaks occured approximately on day of ovulation in all ovulatory cycles induced with sexovid, but LH levels were elevated in only four cases out of failed fourteen cases.
From the results above described, I believe that timely releases of FSH and then LH with such mode as reported by Fukushima et al. and recently by Stevens, might be indispensable for ovulation, even if it were induced.

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Patterns of urinary FSH and LH during the menstrual cycle have not been established, much less those of anovulatory women. We have investigated the effects of various ovulatory agents on urinary hormone excretion.
Urinary FSH of 77 anovulatory patients before treatment was determined by IgarashiMcCann' method and LH by OAAD method and radioimmunoassay.
Most of the patients with amenorrhea second grade showed hyper-FSH or hypo-FSH, and urinary FSH values of other anovulatory types were almost in normal range. The urinary LH values indicated the same tendency as FSH.
Urinary FSH of 30 anovulatory women treated with clomid almost increased after administration, regardless of ovulation. The urinary LH of those increased only in ovulated cases. Therefore, we agree with Jacobson et al. who reported the simultaneous increases of both plasma FSH and LH with clomid treatment, employing radioimmunoassay.
Urinary FSH and LH were also measured in 9 ovulated arid 14 failed cases of anovulatory patients during sexovid (F6066) therapy. FSH levels rose in all cases ovulated during or immediately following sexovid therapies. While, in six cases of fourteen, increased FSH excretion was noted in the absence of ovulation, later than the 20th day of administration. So it was postulated in failed cases that late rises in FSH levels could not sufficiently develop the follicles ready for ovulation, even if LH were simultaneously released. The significant LH peaks occured approximately on day of ovulation in all ovulatory cycles induced with sexovid, but LH levels were elevated in only four cases out of failed fourteen cases.
From the results above described, I believe that timely releases of FSH and then LH with such mode as reported by Fukushima et al. and recently by Stevens, might be indispensable for ovulation, even if it were induced.

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尿中LHを無処理のままradioimmunoassayし測定可能であつた.尿中LHのimmunological activityは酸性, 中性, アルカリ性のいずれでも室温で最低4日間は安定であつた.LHのurinary clearanceを35人について測定し0.30-2.75ml/min.の値を得た.LH urinasy clearaceとcreatinine clearanceは正の相関関係 (相関係数 : 0.551, P<0.01) があり, 腎機能低下によりLHの尿中排泄も低下すると考えられた.

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尿中Testosterone及びEpitestosteroneのGasliquid Chromatographyによる分離定量法の検討を行なつた.Steroid誘導体とColumn (OV-1, OV-17) との比較, 回収試験等を行なつた.正常男子の1日平均排泄量はTestosterone80.6μg (7月), 48.8μg (1月) 及びEpitestosterone45.3μg (7月), 22.8μg (1月) であつた.すなわち, Testosterone及びEpiteststeronいずれも冬期の値は夏期の値にくらべ有意に減少していた. (P<0.05)

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糖尿病の病態形成に “肝が一義的な意義をもつか, 末梢組織がより重要であるか” を追求するために, 健常者におけるブドウ糖経口負荷後と静脈内負荷後の血中メタボライトの変動パターンの差異を指標として, 糖尿病者におけるブドウ糖経口負荷後の血中メタボライトの変動を検索した.その成績より糖尿病者では重症度に応じ, 肝の糖処理機能が減退し, 末梢組織への依存度が亢進することをみとめた.

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摘出肝で認められるインスリンの早期効果には極めて高い門脈内インスリン濃度を必要とする.これは末梢組織よりの代謝情報が全く除外されている為と考え, 著者は更に生理的状態でインスリンの肝効果, 特に早期効果発現機序を追求する目的で特殊な肝-末梢組織標本を作製した.本標本の肝臓は肉眼的外観, 肝組織所見, 胆汁産生能, ATP産生能, 肝酵素活性の変動より, 正常の機能を営むことを確認し所期の目的を果すに足る充分な機能を保持することを認めた.

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McKenzie変法による甲状腺機能充進症未治療群の血中LATS陽性率は66.7%であつた.¹³¹I治療1年以後, 陽性率は徐々に低下する傾向を示した.同一症例の追跡結果でも活性率の低下ないし陰性化が見られた.抗甲状腺剤治療においても略々同様の傾向であつた.これに対し, T₃抑制試験では¹³¹I治療1年以後, 次第に平均抑制率の上昇するのが見られた.また非抑制例にLATS陽性の多いことを認め, 正常抑制反応の見られない理由はLATSによると推定される.しかし治療後明らかに抑制を示した2例にも, 軽度であるがLATS陽性が見られた.

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