In order to study the response of pancreatic alpha cells to the change of blood glucose, plasma pancreatic glucagon levels were measured after glucose loading given orally (50g) or intravenously (25g) in twenty-two normal controls and eighty untreated diabetics. Basal plasma pancreatic glucagon levels did not differ significantly in the two groups. However, oral or intravenous glucose administration caused a decrease in plasma pancreatic glucagon in normal subjects but not in diabetics.
In “moderate” or “severe” diabetics, plasma pancreatic glucagon tended to increase paradoxically following oral glucose loading.
To evaluate the sensitivity of pancreatic alpha cells to glucose, we calculated the index, -ΣΔIRG/ΣΔBS, after oral glucose loading. It was 1.96±0.57 in normal subjects, and significantly higher than in “mild” (0.11±0.05), “moderate” (-0.002±0.06) and “severe” (-0.09±0.07) diabetics.
These results demonstrate the insensitivity of alpha cells to hyperglycemia in patients with diabetes mellitus as compared with normal subjects.

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Sixty-seven mongolian gerbils (Meriones unguiculatus), which seem to resemble the sand rats in the manifestation of diabetic syndrome, were used for observations on the development of diabetic process and on the effect of the long term administration of tolbutamide on it.
The mean blood glucose (158.2±14.7mg/100ml), mean serum NEFA (0.70±0.34mEq/l) and mean serum IRI (68.9±10.2μU/ml) in mongolian gerbils were relatively higher than those in rats.
Diabetes-like processes found in the pancreas of mongolian gerbils were roughly grouped into two main types;(1) the histopathological process in which the fibrosis, initially prominent at perivascular space, spread to the islets, finally producing the islet's cell degeneration, and (2) the process of diffuse islet's hyperplasia. These two processes were considered to differ from each other, the former being affected by tolbutamide and the latter remaining unaffected. After breeding on the diet containing 0.1-0.2% tolbutamide for 6 months, there was a general inclination of an increase of cases of severe pathological findings, and the distribution probabilities of the cases carrying the severe fibrotic process in heart, that is, the process from endothelial cell swelling, medial fibrosis and obliterative changes in cardiac arteries which was resulting in the focal degeneration of cardiac muscle, was significantly higher than in the non-treated group.
It was concluded that mongolian gerbil might be recommended as a model of experimental diabetes and that tolbutamide seemed to have some harmful effects on the diabetes-like process in mongolian gerbils.

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Development and differentiation of rat follicular cells were investigated by lightand electronmicroscopy. The cell-cords growing out from the anterior wall of Rathke's pouch at the 15th day of gestation gradually form the original anterior lobe. Thereafter, its agranular primordial cells spread throughout the gland. Most of them begin to granulate, while some others undergo only mitotic division. The latter tends to congregate and repeat the mitosis for the appointed duration. These cells surround a pseudolumen equipped with microvilli, constituting a cell-mass lacking the basement membrane at the 17, 18 and 20th day of gestation. They may lead to the follicular cells. Pituitary marginal cells resemble in fine structure the follicular cells. The former is a residue of the anterior wall of Rathke's pouch, while the latter is a cluster of the cells differentiating for the specific purpose from the cell-cords. Even in postnatal and infant rats, clusters of ungranulated follicular cells are preserved and may serve as the proliferating center of the gland, based on the frequent observation of mitosis there. After mitotic division, the intercellular spaces enter midway between two daughter cells, leading to the formation of a cluster consisting of small irregular cells. The follicular cells permanently keep their undifferentiated capacity for mitosis through the life course of rats (6-, 21-, 45-, 90-and 400-day-old). The follicular cells located at the periphery of a cluster spontaneously begin to granulate after completing their own mitosis, and finally transform into immature acidophils or basophils through the intermediary stage of ambiguous cells. With granulation, they move towards the outside of the cluster to intermingle among the cells which already have been grown. So-called folliculo-stellate cells, making a framework in the gland, seem to be analogous with the isolated follicular cells without cluster formation. Thyroidectomy and autotransplantation of pituitaries successfully gave rise to granulation and multiplication of the follicular cells, but all our experiments failed to completely disperse them. The follicular cells have two capabilities, cell proliferation and differentiation, both of which are interpreted to be intrinsically balanced. It may be hypothesized in references to our previous accumulated data reported elsewhere that the pituitary belongs to the “renewal cell system” and the follicular cells may be regarded as the “stem cells” of the pituitary.

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The sensitized effect of prestimulation with 16.7mM glucose on insulin release with a slow-rise glucose stimulation from the perifused rat islets of Langerhans was studied, together with the kinetic analysis of insulin release, and the interrelationship between the prestimulation time and the maximal rate of insulin release.
All dose-response relationships which were derived from the dynamics of insulin release from islets prestimulated over various time periods within 60min, showed sigmoidal profiles. Kinetic analyses were performed with Lineweaver-Burk's and Hill's equations. The 30-min prestimulation significantly reduced Hill's constant (n) from 6.2±0.7 of the control to 3.7±0.6 (p<0.05) and also enhanced the logarithmic equilibrium constant (log K) from-5.4±0.6mM^-n to -3.7±0.6mM^-n (p<0.05). However, the Km value was almost the same as that of the control (7.3±0.5mM). On the other hand, the 60-min prestimulation remarkably diminished the Km value and the maximal rate of insulin release to 5.3±0.4mM (p<0.05) and 0.6±0.08μU/ml/islet/min (p<0.005), respectively. The maximal rate of insulin release linearly increased in proportion to the prestimulation time within 30min.
In conclusion, these results suggested that there would be some regularity depending on the prestimulation time in the process of transmission of the insulin-releasing signal in the pancreatic B cell and the accumulation of insulin into the provisional pool such as the labile insulin.

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Eight maturity-onset diabetic patients who had no infections, liver diseases or other endocrine diseases which might affect carbohydrate metabolism were treated with monocomponent lente insulin, which is known to have little antigenicity, until blood sugar was controlled. The diurnal values of the blood sugar (BS) and immunoreactive insulin (IRI) were obtained before treatment and on the third day after the withdrawal of insulin treatment. One patient was dropped from the study because of insulin antibody formation. The total integrated IRI area in the diurnal profile was increased from 98.9±23.7 to 186.1±37.7μU·h/ml (p<0.05), while the total blood sugar area was decreased from 7, 500±1, 200 to 5, 510±1, 214mg·h%(p<0.05). Oral Glucose Tolerance Test on the fourth day after the withdrawal of insulin treatment showed increased IRI response compared to pretreatment.
It is concluded that endogenous insulin secretion could be increased in the diabetic patient by the metabolic control with exogenous insulin injections.

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Corticosterone formation was determined in the reconstructed rat adrenal system which consisted of the mitochondria and post-mitochondrial supernatant fraction (PM-fraction) supported by l-malate, and effect of ACTH and cycloheximide in vivo and cycloheximide, Ca⁺⁺ and sterol carrier protein (SCP) in vitro were examined. Mitochondria isolated from adrenals of rats which received ACTH 15min before sacrifice showed an elevated corticosterone formation. Cycloheximide administration 15min prior to ACTH injection completely blocked the effect of ACTH but in vitro addition of this drug to the incubation mixture did not modify the rate of corticosterone production even at higher concentrations. Since the PM-fraction isolated from adrenals of rats received ACTH or cycloheximide or both did not change the mitochondrial capacity for corticosterone formation, factor (s) which influenced by ACTH administration seemed to be localized in mitochondria. The SCP-bound cholesterol was utilized for corticosterone formation more efficiently than the free cholesterol when added to the incubation mixture, and this might be due to, at least in part, higher rate of binding to the mitochondrial inner membrane of the SCPbound cholesterol.

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Radioimmunoassay of rat luteinizing hormone (LH) in the sera and the anterior pituitaries of normal and castrated males and proestrous females employing different batches of and-LH sera gave the results suggesting heterogeneity of immunoreactive LH (IR-LH). Gel filtration analyses of anterior pituitary extract and pooled sera failed to give positive evidence for the heterogeneity. But when the extracts of normal rat anterior pituitaries were electrofocused and the fractions were assayed, the pituitary glycoprotein hormones, LH, FSH and TSH, were found to consist of several components with different isoelectric points. In electrofocusing patterns of IR-LH, distinct peaks were observed at pH 8.5 (component A), 8.8 (component B), 9.1 (component C) and 9.3-9.4 (component D), and less distinct peaks were observed at pH 7.9 (component A'), 9.6 (component E) and 9.8 (component F). There seemed to be some sexual difference in the relative amounts of these components. Orchiectomy caused marked changes in electrofocusing patterns of IR-LH, i.e., increase of components A', A, B, C and D. The blockade of LH release by estradiol benzoate and progesterone treatment in orchiectomized rats caused a marked increase of component A. At the proestrous LH surge, IR-LH components were evenly released. Radioimmunoassay of IR-LH components with multiple antisera indicated that these antisera had different affinities to these components.

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The effects of cholera enterotoxin (CET) on the male gonad was investigated using testis slices of the rat.
CET stimulated adenylate cyclase activity of the interstitial tissue of the rat testis, increased cyclic AMP (cAMP) production and testosterone release from the interstitial tissue in vitro, thus mimicking effects of LH and human chorionic gonadotropin (hCG). CET also stimulated adenylate cyclase activity of the seminiferous tubules and increased cAMP production, whereas hCG did not exhibit such an effect.
The stimulatory effect of CET on adenylate cyclase activity of the rat testis occurred with a lag time of about 30 min, reached the maximum level after 2-hr incubation and continued over 6 hr. Testosterone release by CET was observed within 1-to 2-hr incubation, when the increase in cAMP was already demonstrated.
The steroidogenic effect of CET was enhanced at low concentration (1 mM) of theophylline and inhibited at high concentration (20mM) of theophylline. Protein synthesis inhibitors (puromycin and cycloheximide) abolished these steroidogenic effect completely, but not cAMP production. Tracer studies of active site (s) of CET in testicular steroidogenesis revealed that the stimulation of testosterone synthesis by CET was, like hCG, due to the stimulation of the conversion of cholesterol to testosterone.
These results suggest that CET stimulates the adenylate cyclase/cAMP system of the interstitial tissue (probably of Leydig cells) and stimulates testosterone synthesis from cholesterol, and that once the adenylate cyclase of Leydig cells has been stimulated, the biosynthetic pathway leading to testosterone is quite similar to that caused by gonadotropins (LH and hCG), although the activation mechanism of adenylate cyclase seems to be different each other.

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The projection from the medial preoptic area to the median eminence of the cat was clarified by electron microscopy. After placing the electrolytic lesion in the preoptic area several kinds of degenerating neuronal processes and terminals were observed in the external layer of the median eminence. The one was dark shrunk terminals containing dense cored vesicles, the other was the dark ones containing myeline figure-like structure. The relationship between catecholamine-containing nerve endings and RH/IH-containing endings in the external layer of the median eminence was discussed.

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[6, 7-³H]-17β-Estradio1-3-glucosiduronate, [6, 7-³H]-estrone-3-glucosiduronate or [6, 7-³H]-estrone was administered intravenously into the rabbit, and analysis and identification of the urinary metabolites were carried out.
In either case, the major urinary metabolite was found to be a diconjugate. The sequential enzymic hydrolysis indicated that this diconjugate was glucosiduronate-Nacetylglucosaminide of 17α-estradiol.
From these results, the conversion of the estrogen glucosiduronate into a diconjugate was thought a rather universal phenomenon in the rabbit.

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In order to examine a possible role of adrenaline (AD) or noradrenaline (NA) in the control of lordosis behavior, lordosis quotient (LQ) was observed daily for 8 consecutive days in the ovariectomized rat given daily 1 or 2μg/0.1ml oil of estradiol benzoate (EB) alone or together with 100μg/0.1ml saline of AD or NA. AD but not NA treated together with EB caused a greater change in the daily LQ than the same dose of EB alone and the change in the daily LQ by daily treatment with both 1μg EB and 100μg AD was equivalent to that by daily treatment with 2μg EB alone. A half mg progesterone (P) could induce the lordosis behavior in the ovariectomized rat treated 48 hr prior with both 1μg EB and 50 or 100μg AD, but not in the one treated with 1μg EB alone. While 50, 100 or 200μg NA or 10μg AD had no effect, 50 or 100 pg AD pretreated together with 2 pg EB produced a markedly higher LQ after p than 2μg EB alone in the ovariectomized rat. This effect of AD on the induction of lordosis behavior was produced only when AD was pretreated simultaneously with EB and AD priming 24 or 43 hr after EB failed to elicit the effect. Therefore, it is suggested that a change of the brain target site in the estrogen sensitivity produced by AD plays a part in the control of lordosis behavior.

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Study on a diurnal rhythm of plasma aldosterone (PA) and plasma renin activity (PRA) was performed in 8 patients with congestive heart failure. All patients had been digitalized and received diuretics under mild sodium restriction. An obvious diurnal rhythm of PA similar to the normal subjects, with the lowest value in the evening and the highest value in the morning, was observed in 7 of 8 cases, while a diurnal rhythm of PRA was obscure except in one case. The PA generally did not run parallel with PRA. Although the reason of the absence of PRA diurnal rhythm in congestive heart failure was not clear, it was considered that reninangiotensin system did not play a significant role for the development of PA diurnal rhythm in congestive heart failure. The determined PA values were entirely within normal range except in 2 cases, although they were administered the potent diuretics chronically. A high PA value was observed only in early morning in one case, while all determined PA values were extremely high in another case with severe congestive heart failure involved in cardiac liver cirrhosis. The PRA values were relatively low in 2 cases, normal in 5 and high in one.

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Administration of 4-8 mg testosterone propionate significantly raised 25-hydroxycalciferol levels in the ultraviolet irradiated rats compared to the ultraviolet irradiated controls, but failed to influence serum 25-hydroxycalciferol levels in the non-irradiated animals. Estradiol benzoate and progesterone did not influence serum 25-hydroxycalciferol levels regardless of the ultraviolet irradiation. These findings implicate that testosterone enhances vitamin D biosynthesis induced by ultraviolet irradiation in rats, in accordance with the clinical observation that males often show higher levels of serum 25-hydroxycalciferol than females.

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