One hundred and twenty-four cases of lymphocytic adenohypophysitis have been reported since 1962. Nearly 60% of the cases in women involved onset of the disease in relation to pregnancy. Headache and visual field defects were the most frequent symptoms. Most patients showed signs of either isolated or multiple anterior pituitary hormone deficiency. ACTH secretion was impaired the most frequently, followed by TSH, gonadotropins, GH and PRL secretion. One third of the cases involved hyperprolactinemia. Tissue from patients with lymphocytic infundibuloneurohypophysitis, also suffering from DI, revealed lymphocytic inflammation limited to the infundibulum, stalk, and neurohypophysis. Twenty of these 124 lymphocytic adenohypophysitis patients developed DI before treatment, and neuroimaging studies revealed thickening of the pituitary stalk in some. At least in a few cases, chronic lymphocytic infiltration occurred in both the infundibuloneurohypophysis and adenohypophysis. Although both lymphocytic adenohypophysitis and infundibuloneurohypophysitis may be caused by autoimmune disorders, the antigens involved may differ.

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PRL surges in female rats have dual effects of luteal function: either inducing luteolysis during the estrous cycle or rescuing and maintaining luteal function during pseudopregnancy. We analyzed these apparent contradictory effects in relation to apoptosis. The detection of fragmented DNA and in situ 3'-end labeling studies were done on corpora lutea (CL) collected from cycling rats at proestrus 1800 h (P1800 specimen) or pseudopregnant rats on day 6 (psp 6). Distinct DNA ladders were observed in P1800 samples as we previously reported, but only slight ones were found in psp 6 specimen. The effect of PRL on the induction of apoptosis was evaluated in vitro with dispersed luteal tissue. CL from cycling rats were exempted from a PRL surge by pre-treating donors with a dopamine agonist. The extent of apoptotic reaction in P1800 specimen depended on the doses of PRL added to the culture medium. In psp 6 specimen, in contrast, PRL suppressed the apoptotic reaction, increased the cell survival rate (MTT assay), and decreased the cell death rate (LDH assay). Furthermore, PRL enhanced 20α-hydroxysteroid dehydrogenase activity in P1800 specimen but suppressed it in psp 6 specimen. In summary, PRL in rats is either an apoptosis-inducer or- suppressor, depending on the functional state of luteal cells.

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We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological changes that occur in the pancreas vs. those in control patients. The mean age was 39.7±13.9 (mean±SD) years, and the duration of IDDM from clinical onset was 13.1±6.5 years. Causes of death included renal complications, infections, acute diabetic complications such as ketoacidosis or hyper- or hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable decreases in the islet area and beta cell area, and a slight decreases in the alpha cell area and preservation of the number of islets. Insulitis was found in only 1 case, representing 25% of the cases with a duration of IDDM of one year or less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and macrophages. Fibrosis, fatty change and atrophy were also found. Although this is not a strictly age- and sex-matched study, the high incidence of lymphocytic infiltration of the exocrine pancreas indicates that the exocrine tissue as well as beta cells is the target of immune reactions in Japanese patients with IDDM.

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Inhibins (α-β_A and α-β_B) and activins (β_A-β_A, β_A-β_B and β_B-β_B) were originally isolated from ovarian follicular fluids as FSH secretion modifiers. Inhibin/activin subunits, α, β_A and β_B, are widely distributed in several tissues, including gonads and brain, and inhibins and activins have been reported to be involved in ovarian or hypothalamic functions. In this study, we established and employed a competitive RT-PCR assay system for rat inhibin/activin subunits by capillary electrophoresis to determine rat hypothalamic and ovarian inhibin/activin subunit mRNA levels during the estrous cycle. Linearity of standards for α, β_A, and β_B subunit assays were between 0.01-0.3amol, 0.003-0.09amol and 0.002-0.02amol of each fragment DNA as a standard, respectively. Hypothalamic β_A subunit mRNA during the estrous morning (1000h) tended to be increased compared with that of the proestrous evening (1700h), although they were not significantly different. Ovarian α subunit mRNA levels tended to be increased during the proestrous morning (1000h) and were significantly increased in the proestrous evening (1700h), compared with diestrus and estrus (P<0.05). Ovarian β_A subunit mRNA was also significantly higher in the proestrous evening, compared with diestrus and estrus (P<0.05), but in the case of β_B subunit mRNA there was no difference among diestrus, proestrus and estrus. We thus established a sensitive competitive RT-PCR system for the measurement of inhibin/activin α, β_A and β_B subunits, and this assay system would be helpful for the study of inhibin/activin action in brain and other tissues where these factors are expressed at low levels.

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To clarify whether glutamic acid decarboxylase65 antibodies (GAD65 Ab) and insulin autoantibodies (IAA) are good predictive markers for insulin-dependency in NIDDM, we studied GAD65 Ab and IAA in NIDDM patients treated with diet alone or in combination with oral hypoglycemic agents. GAD65 Ab were found in 12 of 229 (5.2%, P=0.079 vs. control) NIDDM patients and IAA in 8 of 229 (3.5%). The frequency of GAD65 Ab and IAA positivity in NIDDM did not differ significantly from those of healthy controls (2/150, 1.3%, 2/150, 1.3%, respectively), but the frequency of patients who were positive for either GAD65 Ab or IAA, or both, was significantly higher than that of normal controls (17/229, 7.4% and 4/150, 2.7%, respectively, P<0.05). In addition, the prevalences of GAD65 Ab and of IAA in those patients whose disease durations, since the diagnosis of diabetes, were less than one year were significantly higher than those of controls (4/30, 13.3%, P<0.05, 4/30, 13.3%, P<0.05, respectively). We found no differences between GAD65 Ab positive- and negative-patients in either BMI or serum C-peptide levels. Over a one to five year follow-up period (mean 2.0yrs), serum C- peptide levels gradually decreased necessitating insulin treatment in three of the patients positive for GAD65 Ab and/or IAA (3/17, 17.6%; two were positive for both GAD65 Ab and IAA and one was positive for GAD65 Ab only). In contrast, only five patients negative for the two antibodies developed insulin requirement (5/212, 2.4%, P<0.01). These results suggest that GAD65 Ab and IAA are good markers for predicting the development of insulin dependency in NIDDM patients and that the predictive value for insulin-dependency in NIDDM is enhanced by measuring both antibodies.

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The purpose of this research was to examine the hormonal regulation of the PRL receptor (PRL-R) gene expression in the mammary gland of early pregnant mouse. Following reversetranscription, the quantity of PRL-R mRNA was determined by the competitive polymerase chain reaction. The level of long form PRL-R (PRL-R_L) mRNA changed cyclically with the highest at estrus and the lowest at diestrus II. PRL-R_L mRNA was maintained at high levels for the first 3 days of pregnancy but declined to lower levels on day 5. Mice ovariectomized on day 2 of pregnancy maintained the same level of PRL-R_L mRNA during the 24h-period. The level of PRL-R mRNA increased more than 2- and 2.7-fold with 17β-estradiol and PRL, respectively, and the progesterone concentration decreased its levels to 71% of the vehicle-injected control. The increasing action with 17β- estradiol and PRL was suppressed by administration of progesterone. Mice ovariectomized on day 3 had a 1.8-fold higher level than that of the sham-operated control. The short form of PRL-R remained at low levels throughout the experiments. The results suggested that the expression of the PRL-R gene was suppressed when serum progesterone increased during early pregnancy.

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The clinical features of the first case of a patient with sitosterolemia and generalized eruptive xanthomatosis are described. A six-year-old girl with generalized eruption was referred to the lipid clinic because of the high plasma cholesterol levels determined by the enzymatic method. Neither clinical signs nor results of laboratory examinations appeared to be abnormal, except for the eruption and the increase in the plasma cholesterol concentration. A family survey revealed high plasma cholesterol concentrations in the mother and one of two other siblings. Histological examination showed the eruption to be a xanthoma. Plasma sterol analysis by high-performance liquid chromatography revealed a noticeable increase in plasma plant sterol as well as cholestanol concentrations in the proband and the hypercholesterolemic sibling. The other family members had slightly high plasma sterol concentrations. This is the first case of a sitosterolemic patient with eruptive xanthomatosis. The case indicates that the clinical features of the xanthoma in sitosterolemia are not only tuberous or tendon but also eruptive, and also suggests that sitosterolemia should be considered in the differential diagnosis of hypercholesterolemia in almost every case with tuberous or eruptive xanthoma. The diagnosis is clinically important, since the disease can be treated successfully by diet therapy and bile acid binding resins.

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We report clinical findings and steroidogenic activities in adrenal tissues in 2 cases of AIMAH. Endocrine studies revealed an undetectable level of plasma ACTH and a diminished circadian rhythm of plasma cortisol. A significant increase in plasma cortisol levels in response to ACTH stimulation was observed in both cases. After the administration of metyrapone in one case, urinary excretion of 17- hydroxycorticosteroid (17-OHCS) significantly increased, although the plasma ACTH level did not respond. Computed tomography showed large masses in both adrenal glands, and bilateral uptake was identified on adrenal scintigraphy. The totals for the bilateral adrenal glands were 98g and 105g, respectively, and the left adrenal was larger than the right in both cases. Steroid content in the nodules easured by high performance liquid chromatography (HPLC) showed that the cortisol content was definitely lower than that in cortisol-producing adenoma (CPA) and even in normal adrenals. The activities of cytochrome P450c17, P450c21 and P450c11 were evaluated in one case, and all of them were reduced in the nodules. Especially that of P450c17 was remarkably reduced. These data suggest that cortisol production in AIMAH is inefficient, and that the cause of Cushing's syndrome may be related to the marked increase in the number of cells or bulk of the tumor.

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Noradrenaline (NA) is one of the most important neurotransmitters involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion. In this study, the effects of NA on GnRH secretion, intracellular Ca²⁺ concentrations ([Ca²⁺]i), and membrane potentials were investigated in immortalized hypothalamic neurons (GT1-7) to determine the direct effects of NA on GnRH cells. Cells were perfused in a plastic minicolumn, and GnRH concentrations of the effluents were measured. NA increased the release of GnRH in a dose-dependent manner. Cells were loaded with 4μM Fura 2-AM, and the ratio of the intensities of fluorescent emission at 510nm with excitation at 340 and 380nm was calculated at 100-ms intervals. NA increased the [Ca²⁺]i responses of single GnRH cells dose- dependently. The NA-induced [Ca²⁺]i increase was attenuated in the absence of extracellular calcium and was blocked by the β-adrenergic antagonist propranolol, but not by the α-adrenergic antagonist phentolamine. The cell membrane potential was recorded with a whole-cell patch clamp amplifier with glass-electrodes. NA induced membrane depolarization under current-clamp conditions. The depolarization was also inhibited by propranolol, but not by phentolamine. The results show that NA directly affects the membrane potential of GT1-7 cells via β-adrenergic receptors and induces Ca²⁺ mobilization; these effects stimulate GnRH secretion.

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Gonadotropic activity is present in the placenta of various mammals including humans. Human and equine chorionic gonadotropin (CG) are well characterized and known to be glycoproteinhormones, as are pituitary LH, TSH and FSH. In the rat, however, the placental gonadotropin molecule has not been identified, and in fact the existence of CG in the rodent is still controversial. In the present study, the placental expression of mRNA for CG-like molecules was investigated by PCR with mixed primers designed for the CG-β subunit based on the amino acid sequences common to the rat LH-β, human LH-β, equine LH-β and human CG-β subunits and for the α subunit designed from the rat LH-α subunit. PCR with mRNA extracted from the placenta (day 10 of pregnancy) amplified several bands including cDNA identical to part of rat LH-α and -β. Furthermore, expression of these genes was confirmed in the placenta on days 10, 12, 14, 16, 18 and 20 of pregnancy by PCR with another set of primers specific to rat LH-α and -β and by Southern hybridization with ³²P-labeled cDNAs for LH-α and -β. The specific bands for these subunit mRNAs were amplified in the placenta, as well as in the positive control i.e. the anterior pituitary gland, but were not detected in other tissues including decidual tissue, liver, spleen, intestine, brain and kidney. Expression of the mRNAs was observed in both the junctional and labyrinth zones of the placental tissue. The rat choriocarcinoma cell line Rcho-1 also expressed LH-α but not LH-β regardless of the stage of differentiation in vitro. Here we show the expression of LH-α and -β mRNAs in the rat placenta.

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The causes of hyperprolactinemia, the correlation between serum levels of PRL and thyroid function and magnetic resonance imaging (MRI) of the pituitary were studied in patients with chronic thyroiditis. Seventy-four female patients and 15 normal control women participated in this clinical survey. Fourteen of 74 patients with various thyroid conditions had increased serum PRL. The incidence of hyperprolactinemia in the overt primary hypothyroid group was 42.4% and was significantly higher than in any other group with normal serum thyroxine. There was a close association between the increment in serum PRL and of free triiodothyronine above the basal level after TRH administration. There were 14 patients with hyperprolactinemia in three of which serum PRL was over 60μg/L. PRL producing tumor, severe primary hypothyroidism and liver cirrhosis were detected in these three patients, respectively. These results indicate that the pathogenesis of increased serum PRL was not uniform in patients with Hashimoto's thyroiditis, although there was a correlation between hyperprolactinemia and impaired thyroid function. It is proposed, therefore, to measure and follow serum levels of PRL and MRI of the pituitary in patients with chronic thyroiditis, especially with impaired thyroid function.

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The purpose of this study was to review the phenotypic and endocrine features of a series of patients with ambiguous genitalia or sex-reversal due to gonadal dysgenesis (GD) and to analyse the impact of these on the decision about sex of rearing. This study is a retrospective analysis of 22 patients with GD treated between 1964 and 1994. We assessed external genitalia, internal genital structures, gonadal morphology (n=22), basal and human CG (hCG) stimulated serum testosterone levels (n=11) and serum gonadotropin levels (n=13) in patients with GD. Basal and hCG stimulated testosterone levels were also measured for 43 control patients. There were no significant associations or correlations between internal or external genital phenotype, endocrine function and gonadal morphology. There was a significant association between sex of rearing and external genitalia (P=0.03). Patients with gonadal dysgenesis had significantly lower stimulated/basal testosterone levels than the controls (P=0.0001). Given that the clinical features of various forms of GD overlap considerably, gonadal biopsy should remain the investigation of choice when attempting to define the pathology.

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We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I°HPT) remains unknown. Although the co-existence of MM and I°HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.

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Fetal growth is thought to be independent of the concentration of GH, although circulating levels of GH are high in the human fetus. To elucidate the role of GH in fetal development, levels of GH-binding protein (GHBP) were measured in the serum of nonpregnant and pregnant women and neonates as well as in amniotic fluid obtained at various stages of gestation. Total GHBP (the sum of free GHBP and GHBP bound to GH) is measured by a ligand-mediated immunofunctional assay. GHBP concentrations in adult serum were not changed by pregnancy or the stage of gestation. A significant correlation was observed between the concentration of GHBP in the umbilical artery and vein. No correlation were observed between the GHBP concentration and such measures of fetal growth as fetal weight and fetal age. Although the neonatal concentrations of GHBP were significantly lower than those of pregnant women, no correlation was observed between them. GHBP was also present in the amniotic fluid from early to late gestation at concentrations higher than in the cord serum of the neonate. The amniotic GHBP concentration in late gestation was significantly higher than in early gestation. GHBP appears to be derived from GH receptors of fetal organs (most probably fetal liver). The low level of GHBP in fetal serum may be the result of a decrease in GH receptors caused by high levels of circulating GH. GHBP levels in amniotic fluids may be related to the development or maturation of the fetus.

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Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause infertility. We report a 28-year-old pregnant woman with untreated acromegaly, who was followed up from early pregnancy to delivery. Her pregnancy was uneventful, and she went into spontaneous labor at 38 weeks and delivered a normal infant. Her serum GH levels were further increased in late pregnancy, followed by decreased in postpartum periods, which may be associated with enlargement of pituitary adenoma during pregnancy. In contrast with serum GH, her serum insulin-like growth factor-1 (IGF-1) levels were dissociated with her serum GH levels during late pregnant and postpartum period. Her serum GH and IGF-1 levels in late pregnancy were different from the levels in pregnant women with acromegaly reported previously.

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A 40-year-old woman with adrenal insufficiency was clinically diagnosed and examined with human corticotropin releasing hormone (CRH). This patient with secondary hypo-adrenalism has shown a normal serum cortisol response to exogenous ACTH administration and has been examined with CRH, lysine-vasopressin (LVP) and insulin tolerance test (ITT), respectively. Success in secreting ACTH in response to both CRH and LVP tests, but not ITT, suggests that this disorder was possibly due to a hypothalamic CRH deficiency rather than pituitary corticotroph dysfunction. A combination of the CRH test and ITT has come to play an increasingly significant role in the diagnosis and differential diagnosis of isolated ACTH deficiency syndrome.

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The difference between in vivo and in vitro inhibitory effects on epididymal 5α-reductase was investigated by using epididymides obtained from patients treated with chlormadinone acetate (6- chloro-3, 20-dioxo-4, 6-pregnadien-17-yl acetate, CMA) or ethinylestradiol (17α-ethynyl-1, 3, 5 (10)-estratriene-3, 17β-diol, EE₂). In the in vitro study CMA exhibited competitive inhibition, whereas EE₂ was a noncompetitive inhibitor of human epididymal 5α-reductase. Their in vitro inhibitory effects were weak compared with the effect of finasteride ((-)-N-tert-butyl-3-oxo-4-aza-5α-androst-1-ene-17β carboxamide), a steroidal 5α-reductase inhibitor. The Ki values for CMA, EE₂, and finasteride were 1.4× 10^-5M, 1.5×10^-5M, and 1.3×10^-9M, respectively. Despite their weak in vitro inhibitory potency, CMA and EE₂ strongly inhibited testosterone 5α-reductase in vivo. There were regional differences in inhibitions by CMA and EE₂ on human epididymal 5α-reductase activity depending on the site of the epididymis; the efferent ductules, the head, the body or the tail. In vivo administration of CMA reduced epididymal 5α-reductase activity by 49.7% to 89.4%. In vivo administration of EE₂ reduced epididymal 5α-reductase activity by 82.7% to 96.3%. The apparent Km values for the enzyme in patients treated with CMA or EE₂ and untreated patients did not differ significantly. The Vmax values were significantly decreased in treated patients. These findings suggest that the marked in vivo inhibition of 5α-reductase induced by CMA and EE₂ was not related to the direct action of these compounds, but resulted from a reduction in the amount of the enzyme.

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A VFA mixture solution containing acetate, propionate and butyrate (the molar ratio of acetate, propionate and n-butyrate =61.7:24.3:14.0) was infused into the rumen at various rates (53.5, 107 and 214μmol kg^-1 min^-1) over 6h to examine the effects on basal and growth hormone-releasing factor (GRF, 0.25μg kg^-1)-induced increase in secretion of GH, insulin, glucagon and somatostatin (SRIF) in five castrated male sheep. Intraruminal infusion of the VFA mixture into the 18-h-fasted animals at the rates of 53.5, 107 and 214μmol kg^-1 min^-1 finally raised the total intraruminal VFA concentration from 91.4 to 100.2 (P>0.05), 175.9 (P<0.05) and 234.5 (P<0.05) mmoll^-1, respectively. A preliminary experiment showed that an infusion rate of 107μmol kg^-1 min^-1 mimics the postprandial increase in ruminal VFA. The basal plasma GH concentrations (2 to 4h after the start of VFA infusion) and the area under the profiles for GH release in response to the intravenous GRF injection, which was done 4h after the start of VFA infusion, were significantly decreased by the VFA infusion rates of 107 and 214μmol kg^-1 min^-1. Furthermore, the VFA infusion noticeably increased basal plasma concentrations of insulin, but it scarcely changed the basal levels of glucagon, SRIF and glucose. From these results we conclude that an increase in the ruminal VFA concentration, even within the physiological range, would suppress GH secretion from the ovine anterior pituitary, and that the postprandial rise in the ruminal VFA concentration may be one of the factors normally suppressing GH secretion in sheep.

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Bacterial endotoxin lipopolysaccharide (LPS) is known to suppress gonadotropin secretion and this effect is assumed to be mediated by cytokines. In the present study, we examined whether LPS affected hypothalamic electrical activity associated with LH pulses, and whether tumor necrosis factor-α (TNF-α), a major cytokine induced by LPS, was involved in this process. Ovariectomized rats were fitted with chronically implanted electrode arrays in the mediobasal hypothalamus, and multiunit activity (MUA) was recorded under conscious, unrestrained conditions. Blood samples were withdrawn every 6min through an indwelling atrial catheter for determining serum LH concentrations. Intravenous (iv) injection of LPS (1μg) suppressed characteristic increases (volleys) in MUA associated with LH pulses throughout the experimental period up to 5h. This suppressive effect of LPS on MUA volleys was significantly attenuated by simultaneous intracerebroventricular (icy) injection of the antibody (50ng) to TNF-α through an indwelling cannula in the lateral ventricle. These changes in MUA were faithfully reflected in the LH secretory pattern. Further, either iv (0.4-2μg) or icy (20-250 ng) injection of TNF-α suppressed the frequency of MUA volleys and associated LH pulses in a dose-dependent manner. These results suggest that LPS leads to the suppression of gonadotropin-releasing hormone pulse generator activity through a mechanism involving TNF-α.

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We carried out screening for mutations in the GH-1 gene in 29 sporadic Japanese subjects with severe Isolated Growth Hormone Deficiency (IGHD) by dideoxy fingerprinting (ddF). Three of 29 (- 10%) were heterozygous for each of the following GH-1 gene mutations including: 1) an G→A transition in the third codon of the GH-1 signal peptide of exon 1 resulting in a Threonine to Alanine substitution, 2) a G→A transition in the first base of the donor splice site of IVS 3 (+1G→A) and 3) a G→A transition in the 183rd codon of the GH-1 mature peptide of exon 5 resulting in an Arginine to Histidine substitution. One of three was heterozygous for both mutations of 1) and 2). The IVS 3 (+1G→A)mutation has been previously reported in affected individuals from three unrelated families with IGHD type II (autosomal dominant form). This mutation destroys the GH IVS 3 donor splice site, causing skipping of exon 3 and loss of the codons for amino acids 32-71 of the mature GH peptide. Our findings indicate that 1) ddF screening of genomic DNAs provides a practical tool to detect GH gene mutations and 2) some sporadic cases of IGHD may be caused by GH gene alternations.

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To examine the existence of PRL messenger ribonucleic acid (mRNA) in the mouse placenta during late pregnancy, reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis were carried out followed by nucleotide sequence analysis of cDNA. Total RNA extracted from each tissue was reverse-transcribed, followed by PCR with two oligonucleotide primers specific for a part of mouse PRL (mPRL) cDNA. An amplified RT-PCR product of predicted size was detected in all samples from the placenta of days 16 and 18 pregnant mice. This product was specifically hybridized with a probe overlapping an entire sequence of mPRL cDNA in Southern blot analysis. Nucleotide sequence analysis also provided evidence that the amplified cDNA had a nucleotide sequence completely identical to the mPRL cDNA sequence reported previously. Furthermore, mPRL with a slightly bigger molecular weight than that of pituitary PRL was detected in the placenta of days 12, 14, 16 and 18 pregnancy by immunoblot analysis. These results suggest that PRL mRNA and its translation product are synthesized in mouse placenta during late pregnancy.

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Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important for fetal and postnatal development, but the regulation of circulating IGFs and IGFBPs has not been as thoroughly investigated in the maternal/fetal unit as in the adult animal where nutrition status plays a regulatory role. We used the chronically-catheterized, late-gestation ovine model and compared circulating IGFs and IGFBPs levels, and hepatic IGF-I mRNA levels. Following a five-day maternal fast, both IGF-I and IGF-II levels were decreased in the maternal and fetal circulation (P<0.05), accompanied by a decrease in fetal hepatic IGF-I mRNA levels, but the IGFBP2 level was increased and the IGFBP3 level was decreased in maternal circulation, whereas the IGFBPI level was increased in fetal circulation. In both fed and fasting states, the infusion of glucose (150% of baseline) did not alter IGFs or IGFBPs in either maternal or fetal circulation. To understand the regulation of the endogenous IGF system, rKIGF-I was infused (6.7nmol/kg fetus/h) into the fetal circulation. While maternal IGFs or IGFBPs remained unchanged, IGF-I infusion into fetal circulation resulted in an increase in IGF-I, a decrease in IGF-II, and an overall increase in the IGFBPs (P<0.05). Taken together, circulating IGFs and IGFBPs in the ovine fetus are more sensitive to prolonged nutrient deficit than to a brief glucose increase. The nutrition status therefore regulates the IGF system in maternal and fetal circulation which, in turn, may regulate the nutrient utilization for fetal growth.

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The mutations of the preproparathyroid hormone (preproPTH) gene have been reported to cause some cases of familial isolated hypoparathyroidism (FIH). We investigated the preproPTH gene of five affected subjects of three Japanese kindreds with FIH. The mode of inheritance in FIH of two families was thought to be autosomal dominant, and the FIH of the other was probably inherited in an autosomal recessive manner. Exons 1, 2 and 3 of the preproPTH gene and its exon-intron boundaries were analyzed with either polymerase chain reaction and single strand conformational polymorphism, or direct sequencing of the amplified DNA. We did not detect any mutations in the amplified regions of the preproPTH gene, but an A to G transition in intron 1 was identified in all of the affected subjects. Among them, four were heterozygote, and the other was homozygote. This transition was considered to be a polymorphism, which was the same as reported previously. These results indicate that the preproPTH gene abnormalities are not responsible for FIH in these families. Further studies are required to elucidate whether genes coding for other molecules, such as calcium-sensing receptor, are involved in FIH.

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To clarify whether β₃-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316, 243, a highly specific β₃-adrenoceptor agonist (relative selectivities of 0, 1 and 100, 000 for β₁-, β₂- and β₃-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific β- adrenoceptor agonist, isoproterenol, and by the β₃-specific adrenoceptor agonist, CL316, 243, but the lipolytic sensitivity to CL316, 243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316, 243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD₂ value [-log mol 1^-1 for EC₅₀ (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316, 243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316, 243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.

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To determine the diagnostic implications of measuring the serum thyroglobulin level in patients with a solitary follicular thyroid tumor, a retrospective study was conducted on 122 consecutive patients with a solitary follicular thyroid nodule who underwent thyroidectomy. Data for eight variables were collected: the serum thyroglobulin (Tg) level (μg/l), age, maximum diameter of the nodule, gender, histopathologic type, presence or absence of metastases, macroscopic characteristics of the cut surface of the resected tumor, and smoking habit. Multiple regression analyses were used to investigate the relationships between the serum Tg level and the seven other variables. The diagnostic value of serum Tg was examined by means of receiver operating characteristic (ROC) curves. There were significant correlations between the serum Tg level and the maximum diameter of the nodule, the macroscopic characteristics, and the smoking habit. The sensitivity and specificity of the serum Tg level with a cut-off value of 1, 000μg/l were 57% and 86%, respectively. The likelihood ratio favouring follicular carcinoma associated with the serum Tg>1, 000μg/l was 4.41. Measuring the level of serum Tg may be useful in discriminating follicular carcinoma from follicular adenoma, but since there may be some biases in this retrospective study, the results are less definitive. Further research activities are mandatory to obtain valid evidence.

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We developed an enzyme immunoassay (EIA) for bovine GH (bGH) which is based on indirect competitive immunoassay in culture medium from a bovine pituitary cell culture. 40μl cell culture samples (or bGH standard) and bGH antibody (rabbit anti-bGH) were added to the 96 well microplate coated with secondary antibody (Goat anti-rabbit IgG), and incubated for 24h at 37°C. Biotin-label bGH was added and incubated further for 24h at 37°C, and biotinylated bGH was linked with streptoavidin-peroxidase. Substrates for peroxidase were added to the plate and incubated for 1h at 4°C. The enzyme reaction was stopped with 4N H₂SO₄, and the absorbency at 450nm was measured with an ELISA Reader. The coefficients of intra-assay and inter-assay variations were 4.13-7.59% and 3.71-8.27%, respectively. The regression equation and correlation coefficients with the radioimmunoassay (RIA) were y(RIA)=1.9986×(ETA)-1.3921 and 0.9701(n=27), respectively. Collectively, the present assay provides a reliable alternative to RIA and offers the major advantage of eliminating radioactive reagents and counting equipment.

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We report an unusual case of non-Hodgkin's lymphoma involving both the thyroid and adrenal glands. Malignant infiltration of the glands by B-cell immunoblastic type lymphoma were demonstrated by cytologic findings in needle biopsy. Staging studies showed minor nodal involvement. The patient was treated with combination chemotherapy. Simultaneous involvement of the thyroid and adrenal glands with non-Hodgkin's lymphoma is very rare. In this report, while presenting this rare coexistance, we also want to emphasize that fine-needle aspiration biopsy was useful in the diagnosis.

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