In order to determine whether glucagon has a ketogenic effect through the activation of hepatic ketogenesis or not, 1mg of glucagon was injected intravenously in bolus in normal and in mild or severe (insulin-dependent) diabetics, and plasma levels of 3-hydroxybutyrate (3-OHBA) and free fatty acid (FFA) were measured.
The ketogenic effect of insulin-free glucagon was also tested in the diabetic rats. The effect of (+)-decanoylcarnitine, an inhibitor of hepatic fatty acid oxidation at a step catalyzed by carnitine palmitoyltransferase, upon the ketogenic action of glucagon was also studied in the diabetic rats.
In normal and in mild diabetics, glucagon had no effect on plasma 3-OHBA concentration, but a significant elevation (0.55m mole/l at 30min) was observed following glucagon in insulin-dependent diabetics. The hyperketonemic effect of glucagon was most marked (1.6m mole/l at 30 min) in those who exhibited mild ketonemia before the glucagon injection. No comparable rise of plasma FFA was observed in these subjects. In normal subjects, plasma FFA significantly decreased following glucagon, presumably due to the anti-lipolytic effect of released endogenous insulin.
In normal rats, insulin-free glucagon (0.5mg iv) produced a small but significant rise of plasma levels of FFA and 3-OHBA within 20 min. In diabetic rats, the greater rise of plasma 3-OHBA (1.4m mole/l at 20 min) following glucagon was observed without any rise of FFA. And this rise was abolished by the concomitant injection of (+)-decanoylcarnitine.
These results indicate that glucagon has ketogenic action through the activation of hepatic ketogenesis under conditions where insulinopenia and the absence of endogenous release of insulin coexist.

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Transitory changes in steroidogenesis of isolated rabbit follicles during the course of ovulation were investigated. Follicles of 1 to 2 mm in diameter were mechanically dissected from ovaries of mature virgin rabbits before and 1, 2, 3, 6, 9 and 12 hours after intravenous injection of 100IU/kg of human chorionic gonadotropin (hCG). Five to ten follicles from a rabbit were incubated with 100μCi of acetate-1-¹⁴C at a time and eighty follicles were taken for each time. Incorporation of acetate-14C into pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 20α-dihydroprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol-17β was assessed by the reverse dilution technique with recrystallization to constant specific activity. Overall incorporation of acetate-14C into the ten steroids was at its maximum 3 hours after hCG injection, decreased gradually up to 9 hours and diminished to its minimum level at 12 hours. The highest incorporation into C₂₁ and C₁₈ steroids was observed 2 hours after hCG injection, while that into C₁₉ steroids occurred 6 hours after it. Distribution patterns of incorporation among the individual steroids varied with time, although a preovulatory rise and fall in ¹⁴C incorporation was observed for all steroids analysed. Estradiol-17 β, testosterone and androstenedione were the major products in 0 hour follicles, while C₂₁ steroids were predominant at the first 3 hours with 17-hydroxyprogesterone and pregnenolone the major products. C₂₁ and C₁₉ steroids were actively synthesized between 6 and 9 hours, when pregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone and testosterone were the principal steroids. At the 12th hour after hCG injection, the three androgenic steroids were clearly the major products. It was noted that active androgen production occurred during the latter half of the preovulatory interval.

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This paper represents the results of survey of pituitary diseases in Japan during the 10-year period between 1965 and 1974. All patients who were examined or treated in Japanese general hospitals with more than 80 beds were studied by letters of inquiry. From the study, it was estimated that the total number of patients was as follows: 1130 cases of pituitary dwarfism, 1908 cases of hypopituitarism, 917 cases of acromegaly and gigantism, 745 cases of Cushing's disease (adrenal hyperplasia), 1668 cases of pituitary diabetes insipidus. Detailed information was obtained on about half of these patients.
Among patients with pituitary dwarfism, 84% were idiopathic. Idiopathic cases were observed far more frequently in male patients, while no sexual dominancy was observed in secondary cases. In idiopathic cases, the incidence in pathological conditions at the time of delivery was high. Among secondary cases, the predominant causes we crareniopharyngioma and pinealoma. In adult males with hypopituitarism, 42% were due to pituitary adenomas, 19% to craniopharyngiomas and 14% to pinealomas; in adult females, 42% were due to Sheehan's disease, 30% to pituitary adenomas, 12% to craniopharyngiomas and only 3% to pinealomas. In patients with acromegaly, the male to female ratio was 1.2: 1; histologically, 72% were acidophilic, 13% chromophobe and 15% mixed pituitary adenomas. In this survey of Cushing's disease, Cushing's syndrome due to adrenal tumor was 2: 1. The male to female ratio was 1: 3.3 in hyperplasia and 1: 3.9 in adrenal tumor. In patients with pituitary diabetes insipidus, 55% were secondary, 45% idiopathic and 2% familial. The sex ratio between males and females was 1.4: 1. As causes of secondary cases, 25% were due to pinealomas, 16% craniopharygiomas, 13% trauma and 11% other brain tumors.
It was assumed that most of the diagnosed patients were included in this survey; however, an unknown number of patients were escaped, either because they had been misdiagnosed as other diseases, or because they had not yet received a medical examination.

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The effect of chronic administration of sulpiride on serum human growth hormone (hGH), prolactin and thyroid stimulating hormone (TSH) was examined in 6 normal subjects. Sulpiride was given orally at a dose of 300 mg (t. i. d.) for 30 days. Sulpiride raised serum prolactin levels in all subjects examined. In addition, sulpiride suppressed hGH release induced by L-dopa, although the basal hGH level was not changed. Sulpiride treatment appeared to antagonize partially the inhibitory effect of L-dopa on prolactin release. Following thyrotropin-releasing hormone (TRH) injection, the percent increment in prolactin levels from the baseline in sulpiridetreated subjects was less than in controls without sulpiride. In contrast, both the basal and TRH-stimulated TSH levels were not influenced by sulpiride.
These observations suggest that sulpiride suppressses L-dopa-induced hGH release and stimulates prolactin release, presumably by acting against the dopaminergic mechanism, either on the hypothalamus or on the pituitary. The decreased prolactin response to TRH after sulpiride treatment may indicate a diminished reserve capacity in pituitary prolactin release.

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In order to elucidate the significance of PGs in human labor, PGE₁ and F_2α in biological fluid during human pregnancy and labor were measured by RIA newly developed.
Analytical studies demonstrated that the levels of PGF_2α in maternal plasma were 3.7±2.5ng/ml a few days before parturition, 2.0±0.9ng/ml in the first stage of labor and 1.9±1.4ng/ml at delivery. Thus the concentrations of PGF in maternal plasma showed no significant changes around parturition. On the other hand, the level of PGF_2α. in amniotic fluid represented a significant increase up to 44.27±32.81ng/ml at delivery from 1.45±0.76ng/ml before labor at 38-40 weeks of pregnancy (p<0.05), although it was uncertain whether this elevation was the cause or effect of uterine contraction.
The concentration of PGE₁ ranged from 2 to 14ng/ml around parturition. This indicates that there was little remarkable difference between the levels of PGE₁ in plasma and amniotic fluid during the last month of pregnancy and labor.
Possible involvement of prostaglandins (PGs) in human labor has been discussed.

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Effects of estradiol (E₂). estrone (E₁) and progesterone on serum LH concentrations were investigated in E₂-primed ovariectomized rats. The animal with sc single dose of 20μg E₂ or ‘primed’ animal exhibited 24-hour periodicity of LH secretion, that was low at noon and high in the evening. The second dose of E₂ given 72 hr afterwards potentiated the LH secretion approximately two and a half-folds higher 30hr after treatment. This LH peak was hampered in the rats their t rains conditioned with MPO-roof cut but was neither when the septum ablated. Nevertheless, E₁ injection sienificantly induced an serum LH increase in animals bearing MPO-roof cut. Both estrogen derivative implants in the suprachiasmatic (POSC) and periventricular (POP) portions in the preoptic area evidently induced an increase of serum LH even though the medial preoptic area (MFU) was recently reportea to oe irresponsible to E₂ implant. The present study suggested that the neuronal elements frnm which the transected fibers in the MPO-roof cut animals originated are the main positive feedback sites for E₂ for the induction of the ovulatory LH discharge. The main part of the MPO, the positive site for E₁ and the POSC and POP, the sites for E₂ and E₁ supplementary operate for the completeness of ovulatory LH release.
Proaesterone iniection in 20μg E₂-primed rats as well as progesterone implants in the POSC produced a statistical increase of serum LH.
For the far extent of the results obtained, the neuronal mechanisms concerning 24-hour periodicity of LH secretion and ovulatory LH surge during the estrous cycle are discussed.

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A simple radioreceptor assay for insulin using rat liver membranes as receptor sites, with sufficient specificity, precision, and sensitivity to detect 10ng or 276μU/ml of serum insulin, has been developed. In the presence of standard porcine insulin at the concentration of 1.0ng/tube, approximately 8% of ¹²⁵I-porcine insulin was bound to the plasma membranes and ninety-five per cent of this binding was inhibited by 1.0μg of standard insulin per tube. Four animal insulins inhibited the binding of ¹²⁵I-insulin while ACTH, glucagon, human growth hormone, and oxytocin were inert. Insulin values in dog pancreatic vein sera obtained during and after glucose loading and measured by the present radioreceptor assay agreed well with immunoreactive insulin. The ratio of IRI to the measurement by radioreceptor assay was 1.09±0.18 for the same sera.

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Electrolytic lesions were placed in the hypothalamus of two-day-old female rats. Destruction of the mediobasal part of the preoptic area resulted in persistent vaginal estrus starting on the day of vaginal opening, while lesions placed laterally in the preoptic-anterior hypothalamic area did not interfere with normal cycles. Therefore, the mediobasal hypothalamus is capable of undergoing maturation without any postnatal influence from at least the mediobasal part of the anterior hypothalamus. Destruction of the anterior wall of the third ventricle also caused persistent or prolonged vaginal estrus preceded by normal cycles. The relationship between the loci of lesions and the occurrence of sexual cyclicity was discussed.

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The pituitary basophils of rats were examined electronmicroscopically at various time courses of the following experiments: Acute, subacute and chronic administration or perfusion of TRH and LRH separately or in combination to normal male and ovariectomized female rats as well as thyroidectomy on male rats. The findings showed a sequential, ultrastructural transformation (type I to V) of the basophil which might perform its secretory cycle. The I-type cells represent immature basophils. The II-type cells (correspond to classical TSH-cells) are angular cells in a synthesizing and/or storing phase showing an abundance of secretory granules 100-150nm in diameter. The II/III-type cells come into two categories of cell type, presenting a peripheral vesiculation of the cytoplasm. The III-type cells (correspond to classical LH-cells) are round in shape and possess a number of vesicular structures and secretory granules of about 200nm in diameter throughout the cell body. The III/IV-type cells are characterized by numerous round large cisternae which are filled with fine granulated particles. Secretory granules in these cells are 200-250nm in diameter. The enlarged spherical IV-type cells (correspond to classical FSH-cells) are packed with irregularly expanded endoplasmic reticula. Secretory granules are about 250nm in size. The IV-type cells are presumably at the end stage of granular storage or at the initiation of granular secretion, since there is a transitional cell type (IV/II-type) in which secretory granules are reduced in size (100-150 nm in diameter) and in electron density. Vesicular endoplasmic reticula are infrequently found in the IV/II-type cells, which may be either at the end of the secreting phase or at the subsequent resting phase. The V-type cells appear even in the normal and numerously after repeated or prolonged administrations of TRH or LRH. They may be exhausted basophils. It was not, however, concluded that II-, III-and IVtype cells might correspond to TSH-, LH-and FSH-cells, respectively.
Based on a sequential appearance of the cells mentioned above, we propose a hypothesis: The II-type may transform into the III-type, and subsequently into the IV-type which may come back to the II-type.

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Synthetic thyrotropin-releasing hormone (TRH) tartrate monohydrate was administered by rapid intravenous injection to nine normal males. Plasma thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured before and at selected periods after TRH injection. The mean plasma TSH value immediately prior to TRH injection was 3.5μU/ml and the level 15 min after injection was 14.8μU/ml. The mean plasma LH value immediately prior to TRH injection was 8.0mIU/ml and the level 15 min after injection was 15.0 mIU/ ml. The latter elevation was statistically significant (p<0.01), although it was just above the upper normal range. The mean plasma FSH value immediately prior to TRH injection was 7.7 mIU/ml, and a significant difference was not observed after TRH administration. These results revealed that synthetic TRH tartrate monohydrate influenced the release of LH from the anterior pituitary.

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A 37-year-old woman with typical features of pseudohypoparathyroidism (chronic tetany, paresthesia, persistent hypocalcemia, round face, short stature, short metacarpals and metatarsals, cucutaneous calcification and lack of response to exogenous and endogenous parathyroid hormone as regards urinary phosphate and cyclic AMP excretion) was treated with oral administration of 2μg/day of 1αOH-vitamin D₃. Serum calcium started to rise within 3 days returning to the normal level with disappearance of symptoms referrable to hypocalcemia. Such a favorable effect of a small dose of 1αOH-vitamin D₃ in a patient with typical hypoparathyroidism suggests an important role of disturbance of 1 a-hydroxylation of vitamin D₃ by the kidney in the pathogenesis of calcium and phosphorus abnormality in this disease. Fortyfour cases of pseudohypoparathyroidism in the Japanese literature were briefly reviewed.

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Hypolipidemia caused by Simfibrate feeding for 3 weeks reduced responses of weight and nucleic acid contents to testosterone administration in the ventral and dorsolateral prostates of castrated rats. However, the effect of testosterone on the contents of citrate, fructose, zinc and the activity of testosterone 5α-reductase in the glands of castrated animals was not modified by Simfibrate feeding.

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The effect of methallibure on ovary of H. fossilis was studied. Intraperitoneal administration of methalibure (100μg/g body weight) once a week for 4 weeks was very effective in suppressing the gametogenic and endocrine activities of ovary. The regressed condition of ovary was also apparent in GSI (2.84 to 1.09) readings. This decreased state of activity was further confirmed by reduced ovarian ³²P uptake (28.00 to 18.10). The results obtained after the administration of the above compound on ovary were similar to those of surgical hypophysectomy.

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The serum samples of healthy and insulin-treated subjects were gel-filtrated before and after acid-alcohol extraction. The sera from insulin-treated diabetics were revealed to contain a variable amount of proinsulin-like components (PLC) which were compounded with insulin antibodies and accumulated in the circulation. These PLC-insulin antibody complexes were found to cross-react with C-peptide antiserum. In this study, we have determined serum C-peptide immunoreactivity (CPR) before and after the removal of PLC-insulin antibody complexes, and expressed as total CPR and free CPR, respectively.
The separation of PLC-insulin antibody complexes was performed by the addition of polyethylene glycol to the serum. The free and total CPR values in the subjects never on insulin (7 healthy subjects and 25 adult onset diabetics) were correlated well with each other. The ratios free CPR: total CPR (F/T) were 1.02±0.17 (fasting) and 1.00±0.08 (60min after glucose). In contrast, F/T in insulin-treated diabetics (adult onset 29 cases) were apparently lower than that of the former group ; 0.58± 0.23 (fasting), 0.67±0.22 (60min after glucose). These results provide further evidence that the total CPR values were reflected to a considerable extent by the PLC-insulin antibody complexes. Some cases of insulin-treated diabetics reavealed that over 50% of their serum CPR was attributed to PLC-insulin antibody complexes, and this may be responsible for the higher CPR levels of these cases.
Determination of free CPR may provide more accurate index to evaluate the endogenous insulin responses to various stimuli in some of the insulin-treated diabetics.

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Effects of gamma-aminobutyric acid (GABA) and gamma-amino-β-hydroxybutyric acid (GABOB) on growth hormone (GH) release were investigated in the urethaneanesthetized male rat.
An intraventricular injection of GABA and L-GABOB but not D-GABOB caused a significant increase in plasma GH. An intravenous injection of L-GABOB, at the dose which had no significant effect on basal plasma GH, remarkably enhanced plasma GH response to pentobarbital. These results suggest that GABA and L-GABOB stimulate GH release possibly via the central nervous system in the rat.

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