Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GHreleasing hormone (GHRH), somatostatin (SRIF), GHreleasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GHsecretion are neural endogenousrhythm, sleep, stress, exercise, and nutritional and metabolic signals. GHdeficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GHdeficiency can be treated with recombinant humanGH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GHhypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GHcan be treated by transshenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GHsecretion in combination with or without the surgery. (Internal Medicine 41: 7-13, 2002)

These findings suggest that serum antibodies to 68, 49, 43 kD human anterior pituitary antigen are specific but not so frequently detected in autoimmune lymphocytic hypophysitis.

Abstract.Nitric oxide (NO) has divergent actions under physiological and pathological conditions. NO is rapidly decomposed to nitrite (NO2-) and nitrate (N03-).Since these metabolites are stable, they are good indices of NO production under various conditions. In the present study, we measured N02-and N03-concentrations in the urine collected from 62 hospital controls and 504 healthy subjects by means of a new HPLC system combined with Griess reaction.NOx was the sum of N02-and N03 There was no considerable inter-day variation in urinary NO metabolite levels, and there was close correlation between N02-, N03-and NOx values in spot urine obtained in the early morning and those in 24-h stored urine in hospital controls.Urinary NO metabolite levels, which were corrected by creatinine (Cr) excretion and expressed on a logarithmic scale, showed normal distribution and were independent of sex and age in healthy subjects. The normal ranges of urinary NO2-, N03-and NOx levels were estimated as 17-72 pmol/g Cr,1,023-2,818 pmol/g Cr, and 1,071-2,951pmol/g Cr, respectively. We also found that urinary NO metabolite levels were lower than normal range in patients with various diseases. Key words:Nitric oxide (NO), Nitrite (N02-), Nitrate (N03-), Urine, Healthy subjects (Endocrine Journal 46: 421-428, 1999) NITRIC oxide (NO) is known to have diverse biological effects in vivo. NO acts as a signal messenger or a cytotoxic agent in various tissues [1, 2]. As a signal messenger, NO induces vasodilatation, synaptic plasticity, or neuronal, endocrine and exocrine secretion [3][4][5]. As a cytotoxic agent, NO is involved in the immune response mediated by macrophages and neutrophils [6][7][8][9]. NO is therefore assumed to play a critical role under physiological and pathological conditions [1 , 2, 4].NO is biosynthesized from the terminal guanidine nitrogen of L-arginine in the body [10]. Since NO has an extremely short half life, its direct detection in vivo is hardly possible [11]. NO2-and NO3-are metabolic end products derived from oxidation of NO in aqueous media such as plasma, which are subsequently excreted into urine [12] . Thus the measurement of urinary N02-and N03-levels allows the repeated and non-invasive estimation of systemic NO production in vivo under various conditions. Some previous studies indicated that urinary excretion of NO metabolites was varied by a number of physiological factors [13][14][15][16] or several diseases and experimental conditions [17][18][19][20][21][22][23], but the normal range of urinary NO metabolite levels was not fully elucidated in a general population.In the present study, we measured urinary N02 and NO3-levels in 504 healthy subjects and estimated the normal range of urinary NO metabolites. Drugs Experimental ProceduresSodium azide, sodium nitrite and sodium nitrate were purchased from Nacalai Tesque, Kyoto, Japan.

Insulin resistance is closely related to developing type 2 diabetes mellitus. Visceral fat accumulation is associated with insulin resistance, which affects the free fatty acid (FFA) metabolism. We investigated the interactions among visceral fat accumulation, FFA metabolism and insulin resistance in 20 patients with type 2 diabetes mellitus, including 11 obese and 9 non-obese subjects. Body fat distribution was estimated by measuring the areas of both subcutaneous and visceral fat mass on abdominal computed tomography at the umbilical level. Glucose infusion rate (GIR) and plasma FFA responses to insulin were determined as an index of insulin resistance and anti-lipolytic action, respectively, in a euglycemic hyperinsulinemic clamp study. There was an inverse correlation between GIR and insulin-induced decrease in plasma FFA in all diabetic patients (r = -0.652, P < 0.01). Visceral fat mass area was well correlated with GIR (r = -0.583, P < 0.01) and insulin-induced decrease in plasma FFA (r = 0.724, P < 0.001), whereas subcutaneous fat mass area was not correlated either with GIR or plasma FFA decrease. These findings suggest that visceral fat accumulation results in increasing the resistance against the anti-lipolytic action of insulin, and that FFA metabolism is closely related with glucose utilization in patients with type 2 diabetes mellitus.

Abstract.We studied the possible relationship between nitric oxide (NO) production and insulin resistance in patients with type 2 diabetes mellitus. Urine NO metabolites (NOx) were measured as an index for NO production by HPLC combined with a Cd column, Griess reaction and a spectrophotometer in 403 healthy control subjects and 102 hospitalized patients with type 2 diabetes. Glucose infusion rate (GIR) was measured as a reverse index for insulin resistance by euglycemic glucose clamp study using an artificial pancreas in 20 of 102 diabetic patients. Urine NOx was lower in the patients with type 2 diabetes than in healthy control subjects (mean±SE: 3.18±0.02 versus 3.25±0.01 log[pmol/gCr], p<0.01).Urine NOx was correlated with body mass index (BMI) in 102 diabetic patients (r= -0.372, p <0.00l), but not related to either age, sex, fasting plasma glucose, HbAI~ or blood pressure. Urine NOx was correlated with GIR independent of BMI in 20 diabetic patients (r=0.774, P<0.0001).These findings suggest that NO production is closely related with insulin resistance in patients with type 2 diabetes.