Although TSH is the major regulator of thyroid growth and function, the role of TSH in thyroid cell growth in vitro is controversial. Recent studies have shown that a number of growth factors, cytokines, vitamins, hormones and other reagents including iodide, lithium or retinoids modulate proliferation of cultured thyroid cells. Insulin-like growth factors (IGFs) stimulate growth of thyroid cells from a variety of species and also enhance expression of differentiated functions stimulated by TSH. Epidermal growth factor (EGF), fibroblast growth factor (FGF), and Transforming growth factor (TGF)-α are also mitogens to thyroid cells, but they are inhibitory to differentiated functions. In contrast, TGF-β is a potent inhibitor to thyroid cell growth and functions. Indirect evidence suggests that these growth factors are involved in growth regulation of normal and neoplastic thyroid cell growth in autocrine/paracrine manner.

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Cloning of the thyroid hormone receptor and its identification as a cellular counterpart of the viral oncogene v-erbA was a major breakthrough in the study of thyroid hormone action. However, contrary to our initial expectations, many astonishing findings which have accumulated since the receptor cloning, especially the presence of two receptor types, made the elucidation of the thyroid hormone action extremely complicated. In this paper, we mainly did a phylogenic comparison of the amino acid sequence between α-and β-type receptor from Xenopus laevis to humans, hoping to obtain some clue to clarify the functional differences between these receptors. There are several consistent amino acid differences between α-and β-receptor through species in the DNA binding domain, one of which is non-conservative and is located in the portion supposed to be critical to the protein-protein interaction. We believe that clarification of the physiological significance of the presence of two receptor types will facilitate the study of thyroid hormone action.

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A 43-year-old man was admitted to our hospital in January, 1991 for further examination of polydipsia, polyuria and hypertension. He had had a personal history of hypertension since 1976 and of diabetes mellitus since 1982. Physical examination and routine laboratory studies showed that the patient was characterized by asymptomatic hypertension in the presence of hypokalemia and increased urinary potassium excretion. Plasma aldosterone concentrations (PAC) were elevated and plasma renin activity (PRA) was suppressed, resulting in a considerable increase in the ratio of PAC to PRA. PAC was not normally suppressed by saline infusion (2 1/2h, iv). PRA remained suppressed and PAC did not rise after stimulation with iv injection of furosemide (40mg) in combination with walking for 60min. PAC was increased in response to ACTH injection (0.25mg, iv) but not suppressed by dexamethasone administration (2 and 8mg/day, po). PAC did not rise after iv infusion of angiotensin II (20ng/kg/min for 30min). Venous sampling showed that PAC was considerably elevated in the bilateral adrenal vein. CT and MRI demonstrated tumor mass in the bilateral adrenal gland and the remaining normal portion in the left adrenal gland. Scintigraphic imaging with ¹³³I-adosterol during dexamethasone suppression provided bilateral uptake in the adrenals. Oral administration of spironolactone (375mg/day) suppressed blood pressure and elevated PRA and serum potassium. Elevated PCA and PRA levels as well as hypertension were corrected by right-total and left-subtotal adrenalectomy performed in March, 1991. However, impaired glucose tolerance was not changed after surgery, and plasma glucose levels were well controlled with a small dose of insulin (9U/day). Pathological studies revealed adrenocortical adenoma cells of clear cell type with spironolactone bodies in the bilateral adrenal tumors. These findings indicate that this is a very rare case of primary aldosteronism due to bilateral functioning adrenocortical adenomas, which is accompanied by diabetes mellitus.

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Although various mediators such as platelet activating factor, anaphylatoxin and cytokines are considered to be involved in the pathology of endotoxin-induced shock, an endothelium-derived relaxing factor (EDRF), nitric oxide (NO) or its related substance, has recently been shown as a vasodilating factor that is produced from L-arginine. On the other hand, N^G-nitro-L-arginine (L-NNA) is shown to inhibit NO production from L-arginine. Thus, in order to examine a possible involvement of NO in the shock, the effect of L-NNA administration was studied on the hemodynamics and plasma hormone levels during endotoxin-induced shock in anesthetized dogs. Twenty-five mongrel dogs were divided into the following 5 groups;(1) In group C, only physiological saline was administered.(2) In group L, a bolus injection of L-NNA (4mg/kg B. W.) was followed by a continuous infusion of the agent (0.05mg/kg B. W./min) for 120min.(3) In group E, lipopolysaccharide (LPS) E. Coli 011: B4 2.625mg/kg body weight was administered.(4) In group LE, L-NNA administration (bolus and continuous) the same as in group L was started 5min before the injection of LPS.(5) In group EL, L-NNA administration (bolus and continuous) was started 5min after the injection of LPS.
In Group LE, MAP decreased to-45.9mmHg 5min after LPS injection and-33.0mmHg 120min from pre-level. The levels of MAP from 15 to 90min were significantly higher than those in Group E. In Group EL, MAP decreased to -61.4mmHg 5min after LPS injection and this low level (-59.5mmHg) continued for 120min. A protecting effect of L-NNA against LPS-induced hypotension was clearly observed only when administration of the agent was started before LPS injection. These results indicated that LPS induced shock could be produced by a possible increase of NO production in the vascular endothelial cells.
The other finding in the present experiment using anesthetized animals was that L-NNA had a stimulatory action on some endocrine systems such as the renin-aldosterone system and pituitary-adrenal axis, although the exact mechanism of this action of L-NNA on such systems was unclear.

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The functional assessment of GH receptor has been previously performed by GH-induced somatomedine (SM) generation test. There is a specific GH receptor on adipocytes, and GH induces lipolysis with an increment of plasma free fatty acid (FFA). In this report, we examined GH and FFA responses to GRF loading tests and GH-binding protein, which reflects the tissue GH-receptor concentration, in 30 short children, and we evaluated the lipolysis mediated by GH and GH-receptor axis. Following GRF administration, there was a definite increase in plasma FFA levels, which mainly consisted of palmitic acid and oleic acid on HPLC analysis. In the group of GH high responders, peak GH levels more than 30ng/ml, the increments of FFA were apparently more than those in the GH low responders, peak GH levels less than 30ng/ml. There was a significant correlation between the integrated GH secretion and the integrated FFA net In the GH low responders, the integrated FFA net-increments significantly correlated with their serum GH-binding protein activities. The net increments of FFA were also correlated with basal SM-C levels. In a case of GH-resistant dwarfism, in which GH-binding protein activity was markedly reduced, the patient's GH secretion to GRF as high as 51ng/ml did not induce any increment of FFA levels.
These results suggest that FFA responses to GRF loading depend on the integrated GH secretion and tissue GH-receptor content. FFA measurements in GRF test samples may be a simple and useful method for the functional assessment of GH and GH-receptor axis.

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The aim of this study was to determine the effect of angiotensin-converting-enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT) Ten patients (5 men and 5 women) with EHT (3 with mild diabetes and 2 with borderline glucose tolerance) participated. We measured insulin sensitivity using the two-hour euglycemic-hyperinsulinemic clamp technique and plasma glucose and insulin responses to a 75g oral glucose tolerance test (75gOGTT) before and after 6-8 weeks of treatment with alacepril (dose, 50mg/day). Glucose infusion rate (GIR) during the last 30min of the clamp study increased from 5.83±0.70 to 6.59±0.65mg per kilogram of body weight per minute (P<0.05) after treatment with alacepril. The insulin-sensitivity index, which was calculated by dividing the GIR by the mean insulin concentration during the same period of the clamp, also increased from 5.91±0.66 to 7.20±0.90 (P<0.05) after treatment with alacepril. Plasma glucose responses to a 75gOGTT were changed from diabetic pattern to borderline pattern in two patients and from borderline pattern to normal pattern in one patient after treatment with alacepril. Body weight did not significantly change throughout the study in any of the patients studied.
Our study demonstrated that alacepril significantly improves insulin sensitivity in patients with EHT.

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