Search PubMed⌕ Search

Biomedical subjects

J G Won

Publications and source records attributed to J G Won.

18 recordsLinked to original sources
PubMed2001

The stimulatory effect of vasoactive intestinal peptides on the cortisol production of guinea pig Zona fasciculata cells: an extra-ACTH regulatory model of the adrenocortical function.

The effect of vasoactive intestinal peptide (VIP) on cortisol production was studied in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells. In ZF cells, VIP stimulates cortisol secretion and enhances the steroidogenic action of ACTH. Compared to ACTH on an equal molar basis, the cortisol-stimulatory effect of VIP is at least 10-fold less potent. As VIP exhibits a wide range of biological actions with widespread distribution in the body, the steroidogenic action of VIP on the adrenal glands is not tissue-specific. There are VIP receptors in ZF cells. With the aid of a VIP receptor antagonist, we found that ACTH and VIP mutually bind each other's receptors with an affinity-ranking order of ACTH > VIP receptor antagonist > VIP. VIP stimulates cortisol production most likely through the cyclic AMP (cAMP) signaling pathway. Both ACTH receptors and the VIP receptors bind VIP receptor antagonist more avidly than VIP, but the bindings do not lead to a consequential effect on cAMP production and cortisol secretion. However, the VIP receptor antagonist counteracted ACTH and VIP to lower both cAMP and cortisol production. In addition, ASIF and BNP-32, which are the proven ACTH receptor antagonists, reduced the cortisol-stimulatory effect of ACTH and VIP. These results suggest that besides ACTH, VIP be an important factor in regulating the cortisol secretion from the adrenal cortex at the site of ACTH receptors. In cases with hypercortisolemia being detected concomitantly with normal or low ACTH levels, we may need to investigate the influential role of VIP.

Adrenal Cortex↗
PubMed2000

Further study of aldosterone secretion-inhibitory factor and brain natriuretic peptide on cortisol production of guinea pig zona fasciculata cells.

The suppressive effect of aldosterone secretion-inhibitory factor (ASIF) and brain natriuretic peptide (BNP-32) on the basal and ACTH-stimulated cortisol production in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells was further studied. The binding of 125I-labeled ACTH(1-24) and ASIF to ZF cells was found to be displaced by ACTH(1-24), [Phe2, Nle4 and Ala24]-ACTH(1-24), ASIF, and BNP in a concentration-dependent manner. The binding of 125I-labeled [Phe2, Nle4 and Ala24]-ACTH(1-24) to two transformed clones of mammalian cells expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF and BNP. ASIF and BNP significantly suppressed ACTH-stimulated cAMP production in ZF cells. The 10- and 30-min cellular changes in cAMP induced by ASIF and BNP did not correlate in the rank order with the ultimate magnitude of cortisol suppression observed in ZF cells after a 24-hour treatment with these peptides. Nevertheless, the results did conform to the signaling mechanism of their action. Overall, the findings clearly demonstrated that ASIF and BNP suppressed the adrenocortical function and inhibited ACTH for their antagonistic action against ACTH primarily at the ACTH receptor site. These results support the notion that a physiological role of adrenal medulla in regulating the adrenocortical function may be mediated by the neuropeptides through a paracrine pathway.

Animals↗
PubMed1999

Hürthle cell carcinoma of the thyroid gland with extensive tumor necrosis: a case report.

Hürthle cell neoplasm of the thyroid gland is rarely associated with tumor necrosis. We report a case of Hürthle cell carcinoma of the thyroid gland with extensive necrosis. An 82-year-old man had had a right neck mass for more than 10 years. Approximately two to three weeks before he was hospitalized, this neck mass became progressively enlarged. An 131I scan could not demonstrate the right lobe of the thyroid gland, while the contralateral lobe was unremarkable. A 99mTc-sestamibi scan showed increased uptake on the lesion side. Fine needle aspiration cytology showed necrosis with macrophages in the initial aspirate, and the secondary aspirate appeared suspicious for a Hürthle cell tumor. The patient had a total thyroidectomy, and the pathology proved to be Hürthle cell carcinoma with tumor necrosis.

Adenocarcinoma↗
PubMed1998

Genitourinary tuberculosis complicated with adrenal involvement and primary adrenocortical insufficiency: a case report.

Genitourinary tuberculosis (TB) rarely involves the adrenal gland. A 67-year-old man presented with progressively hyperpigmented skin and an enlarged mass over both testes. Early morning plasma cortisol concentration was low and adrenocorticotropic hormone (ACTH) concentration was high. A rapid ACTH stimulation test revealed the absence of plasma cortisol response and confirmed a diagnosis of primary adrenocortical insufficiency. An abdomen computed tomography (CT) scan disclosed enlargement of the right adrenal gland and punctuate calcification over the left one. This is compatible with tuberculous adrenalitis. Currettage biopsy of the prostate demonstrated chronic granulomatous inflammation with Langerhan's giant cells, but without TB bacilli. Anti-TB treatment, in addition to glucocorticoid and mineralocorticoid replacement, was administered. The testicular mass decreased progressively though the results of a subsequent ACTH stimulation test, six months later, disclosed no significant change. A follow-up CT scan, one and a half years later, showed a decrease in the size of the right adrenal mass.

Addison Disease↗
PubMed1997

Selective intra-arterial calcium injection in the investigation of adult nesidioblastosis: a case report.

A 69-year-old man with recurrent hypoglycaemia had inappropriately elevated plasma insulin level during a symptomatic hypoglycaemia, but had a negative prolonged fast. Computerized tomography (CT) of the abdomen revealed a nodular lesion over the body of pancreas, whereas pancreatic arteriography failed to show tumour blush. Hence, arterial stimulation (with calcium) and venous sampling (ASVS) was performed and a brisk response of plasma insulin level was found when calcium was injected both into the splenic and the superior mesenteric arteries. Since no tumour was found during the operation, the patient received subtotal distal pancreatectomy. Pathological examination of the resected tissue disclosed a typical finding of nesidioblastosis. We suggest that selective intra-arterial calcium injection with hepatic venous sampling for insulin gradients is useful for the diagnosis of adult nesidioblastosis.

Aged↗
PubMed1995

Role of inositol trisphosphate-sensitive calcium stores in the regulation of adrenocorticotropin secretion by perifused rat anterior pituitary cells.

Intracellular Ca2+ (Cai2+) stores contribute significantly to Ca2+ signaling in many types of cells. We studied the role of inositol trisphosphate (InsP3)-sensitive Ca2+ stores, a principal Cai2+ store that presumably is within the endoplasmic reticulum (ER), in cell signaling by examining the effect of thapsigargin (Tg), an ER Ca2+ pump inhibitor that depletes the ER Ca2+ pool, on ACTH secretion. Preincubation for 6-24 h with 2-20 nM Tg had no effect on the resting cytosolic free Ca2+ concentrations ([Cai2+]) but inhibited the ionomycin-stimulated spike-type increase in [Cai2+], which is mediated by InsP3-independent Cai2+ release from the ER, in a dose-dependent (IC50, 4 nM) and time-dependent manner. In ER Cai(2+)-depleted cells, the spike phase (initial 5 min) of the ACTH secretory response to arginine vasopressin (AVP), which is mediated by InsP3-induced Cai2+ release, was also attenuated (IC50, 7.3 nM). However, the spike phase of the ACTH secretory response to AVP was inhibited to a much greater degree than the spike-type response to ionomycin, suggesting that ER Cai2+ stores might have functions other than simply providing Ca2+ for InsP3-stimulated Cai2+ release. Tg pretreatment (IC50, 12 nM) also markedly inhibited the sustained plateau (final 15-min) phase of the ACTH secretory response to AVP, which is mediated by diacylglycerol-induced activation of protein kinase C and subsequent influx of extracellular Ca2+ via L-type voltage-sensitive Ca2+ channels (VSCC), but had no effect on the sustained (full 20 min) response to dioctanoylglycerol that directly activates protein kinase C. Tg had no effect on specific cell binding of [125I]AVP or on specific cell binding of [3H]phorbol 12,13-dibutyrate (except at 20 nM Tg), an index of protein kinase C concentration, or on protein kinase C activity. AVP significantly stimulated inositol trisphosphate accumulation, but pretreatment with Tg completely abolished this effect of AVP, whereas [3H]myoinositol incorporation into membrane-associated inositol lipids and inositol phosphates was unaffected. Thus, Tg-induced depletion of ER Cai2+ stores inhibited both the spike and plateau phases of the ACTH secretory response to AVP, presumably by inhibiting phospholipase C activity and the resulting generation of InsP3 and diacylglycerol. Preincubation with Tg inhibited, in a dose-dependent (IC50, 13 nM) and time-dependent manner, the sustained ACTH secretory response to corticotropin-releasing hormone (CRH) that is mediated by cAMP-induced activation of protein kinase A and Cae2+ influx via L-type VSCC, and the sustained response to forskolin, which directly activates adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Role of lipoxygenase metabolites of arachidonic acid in the regulation of adrenocorticotropin secretion by perifused rat anterior pituitary cells.

Arachidonic acid metabolites have been implicated in the regulation of ACTH secretion. To define further which eicosanoid(s) is primarily involved, we examined the effects of both inhibitors of the three arachidonate metabolic pathways (cyclooxygenase, lipoxygenase, and epoxygenase) and specific eicosanoid products on ACTH secretion by rat pituitary corticotrophs in a microperifusion system. CRF stimulates sustained ACTH release that is mediated by protein kinase-A-induced extracellular Ca2+ (Cae2+) influx via L-type voltage-sensitive calcium channels (VSCC). Arginine vasopressin (AVP) stimulates an initial spike phase of ACTH release that presumably is mediated by inositol 1,4,5-trisphosphate-induced intracellular Ca2+ (Cai2+) release, followed by a sustained plateau phase of ACTH release that is mediated by protein kinase-C-induced Cae2+ influx via L-type VSCC. Pretreatment for 15 min with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 50 microM), but not the cyclooxygenase inhibitor indomethacin (10 microM) or the epoxygenase inhibitor SKF525A (100 microM) inhibited the sustained response to CRF by 48% and the initial spike response to AVP by 38%. NDGA-induced inhibition was not reversed by indomethacin or SKF525A, alone or in combination, precluding arachidonate shunting into other pathways. However, the results suggested that epoxygenase metabolites may have a minor stimulatory and cyclooxygenase metabolites may have a minor inhibitory effect on ACTH secretion. Preexposure to NDGA suppressed by 43% the sustained response to 8-bromo-cAMP, which directly activates protein kinase-A; by 57% the sustained response to dioctanolglycerol, which directly activates protein kinase-C; and by 59% the spike-type response to ionomycin, which releases Cai2+ by an inositol 1,4,5-trisphosphate-independent mechanism. These results suggest that NDGA either inhibits the production of a lipoxygenase metabolite involved in Cae2+ influx and/or Cai2+ release or acts other than by inhibiting lipoxygenase, such as by directly blocking membrane transport of Cae2+. The three major lipoxygenase metabolites tested, 5(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acid (HETE), all stimulated sustained ACTH release in a dose-dependent manner. At a concentration of 2 microM, 12(S)-HETE was 4.7 and 2.5 times more potent than 5(S)- and 15(S)-HETE, respectively, and completely reversed NDGA inhibition of both CRF- and AVP-stimulated ACTH secretion. The ACTH-releasing activity of 12(S)-HETE was inhibited 26% by removing Cae2+ and 54% by both removing Cae2+ and depleting Cai2+, indicating either that 12(S)-HETE facilitates transmembrane Ca2+ transfer or that increased cytosolic Ca2+ is necessary for 12(S)-HETE's action.(ABSTRACT TRUNCATED AT 400 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Effect of protein kinase-C depletion on inositol trisphosphate-mediated and cyclic adenosine 3',5'-monophosphate-dependent protein kinase-mediated adrenocorticotropin secretion.

We studied the effect of Ca2+/phospholipid-dependent protein kinase-C (protein kinase-C) down-regulation by chronic exposure to phorbol 12-myristate 13-acetate (PMA) on ACTH secretion by dispersed male rat anterior pituitary cells in a microperifusion system. Preincubation for 24 h and preperifusion for 3 h with 0.1 and 1 microM PMA significantly inhibited (by 85% and 91%, respectively) the specific cell binding of [3H]phorbol 12,13-dibutyrate, an index of protein kinase-C concentration, and significantly reduced (by 101% and 20%, respectively) the sustained plateau (final 15-min) phase of the ACTH response to arginine vasopressin (AVP) and (by 56% and 54%, respectively) the sustained (full 20-min) response to dioctanoylglycerol (DOG), both of which are mediated by protein kinase-C activation. In contrast, the spike (initial 5-min) phase of the response to AVP, which is mediated by intracellular Ca2+ release from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores, was significantly increased (by 112% and 99%, respectively), but the spike-type response to ionomycin, which releases intracellular Ca2+ by an InsP3-independent mechanism, was unaffected. AVP significantly stimulated inositol bisphosphate and InsP3, but not inositol monophosphate, accumulation, and PMA pretreatment significantly enhanced their AVP-stimulated accumulation (by 86%, 34%, and 78%, respectively), an effect that was abolished by simultaneous preperifusion with PMA and cycloheximide to inhibit new protein synthesis. Enhancement of the spike phase response to AVP and AVP-stimulated InsP3 accumulation were lost within 1 h of PMA removal, but [3H]phorbol 12,13-dibutyrate binding and the sustained responses to AVP and DOG remained suppressed after 3 h. Pretreatment with 0.1 and 1 microM PMA slightly reduced the sustained responses to CRF (by 29% and 16%, respectively) and 8-bromo-cAMP (by 8% and 12%, respectively), which are mediated by protein kinase-A activation and extracellular Ca2+ influx via L-type voltage-sensitive Ca2+ channels, but not the response to KCl, which is mediated by extracellular Ca2+ influx via all types of voltage-sensitive Ca2+ channels. The sustained response to CRF was still suppressed 1 h after PMA removal, but returned to the control level by 3 h. When new protein synthesis was inhibited by preperifusion with cycloheximide alone for 3 h after 24-h PMA pretreatment, recovery from the effects of PMA was abolished. Three-hour exposure to cycloheximide without PMA pretreatment inhibited the sustained responses to CRF, AVP, and DOG, but not the spite response to AVP.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

The establishment of radioimmunoassay of cyclic AMP.

Succinyl cyclic AMP, coupled with human albumin, was injected into rabbit to elicit antibodies to the cyclic nucleotide hapten. The succinyl cyclic nucleotides were conjugated to human albumin through a carbodiimide coupling procedure. The radioligand was prepared essentially by the modified method of Hunter and Greenwood. The resulting radiolabeled 125-ScAMP-TME was subsequently purified by reverse phase chromatography on Seppak C18 cartridge and used as tracers. Free and bound form of labeled antigens in the assay system were separated according to their differences in adsorption to solid material, i.e., charcoal. The antisera in routine use had 8% cross-reactivity with cyclic GMP, but had no cross-reactivity with ADP, 5'-AMP or ATP. The sensitivity of the assay in standard was around 0.05 pmol/ml. The sequential saturation analysis system was superior to the equilibrium study in terms of its sensitivity in standard curve determination. The media dilution and recovery studies showed good parallelism with the standard curve. The intra-assay and inter-assay coefficient variations were 5% and 7%, respectively. It showed that a significant increase in tracer binding to the antibodies in equilibrium incubating system was obtained when they were incubated at 4 degrees C for up to 72 hours. When the standard curve was derived for Scatchard plot analysis, Kd of the curve decreased inversely with the increase of the antibodies diluted, the total binding capacity of the antibody would not alter. A thyroid-stimulating hormone produced a normal response of cyclic AMP concentrations in FRTL-5 tissue cultures.

Animals↗
PubMed1991

Insulin treatment improved glucose-induced insulin release in elderly non-insulin-dependent diabetes mellitus, secondary failure to oral hypoglycemic agents.

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.

Administration, Oral↗
PubMed1990

Roles of intracellular and extracellular calcium in the kinetic profile of adrenocorticotropin secretion by perifused rat anterior pituitary cells. I. Corticotropin-releasing factor stimulation.

We examined the effects of removing extracellular Ca2+ (Ca2+e), depleting intracellular Ca2+ (Ca2+i), inhibiting Ca2(+)-dependent calmodulin, blocking voltage-sensitive Ca2+ channels, and combining Ca2+i depletion with exposure to glucocorticoid on the secretion of ACTH by perifused dispersed rat anterior pituitary cells stimulated with ovine CRF and 8-bromo-cAMP (8-Br-cAMP). A time-course analysis of the effect of perifusing the cells for 60 min with Ca2(+)-free medium on 10 nM CRF-stimulated ACTH release revealed that inhibition required about 3 min to begin and about 40 min to reach maximal effect. Within 2 min of restoring Ca2+ to the medium, ACTH secretion rebounded for about 5 min before falling to the pre-Ca2+e removal rate. A similar pattern and time course were observed when Ca2+e was more completely removed by perifusing the cells with Ca2(+)-free medium containing 2 mM EGTA, except that greater suppression was observed. Removing Ca2+e reduced CRF- and 5 mM 8-Br-cAMP-induced ACTH release by 54% and 49%, respectively, and delayed by 1 min the response to 8-Br-cAMP, but not that to CRF. Perifusing 0.2 mM nimodipine, a dihydropyridine Ca2+ channel blocker, before and after restoration of Ca2+ to the Ca2(+)-free medium inhibited ACTH release by 40-48%, and the blockade persisted for at least 70 min after nimodipine was removed from the medium. When intracellular Ca2+ was depleted by perifusing the cells with Ca2(+)-free/EGTA medium containing the Ca2+ ionophore A23187 to facilitate the efflux of Ca2+i, CRF- and 8-Br-cAMP-stimulated ACTH release were reduced by 70% and 71%, respectively, and the responses to both agents were delayed by 1 min. Preperifusion of the cells with 5 microM penfluridol, a calmodulin inhibitor, reduced CRF- and 8-Br-cAMP-induced ACTH release by 54% and 41%, respectively. The combination of Ca2+i depletion and perifusion with 100 nM dexamethasone, a maximally inhibitory concentration, inhibited CRF- and 8-Br-cAMP-stimulated ACTH release by 82% and 83%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Roles of intracellular and extracellular calcium in the kinetic profile of adrenocorticotropin secretion by perifused rat anterior pituitary cells. II. Arginine vasopressin, oxytocin, and angiotensin-II stimulation.

We examined the effects of removing extracellular Ca2+ (Ca2+e), depleting intracellular Ca2+ (Ca2+i), inhibiting cAMP-dependent calmodulin, and blocking voltage-sensitive Ca2+ channels on the secretion of ACTH by perifused dispersed rat anterior pituitary cells. The cells were stimulated with synthetic arginine vasopressin (AVP), oxytocin (OT), and angiotensin-II (AII), all of which are thought to act via the Ca2+/inositol phosphate-dependent protein kinase-C pathway, with synthetic ovine CRF, which acts via the cAMP-dependent protein kinase-A pathway, and with dioctanoylglycerol, which directly activates protein kinase-C. All three secretagogues elicited an initial spike phase ACTH secretory response that peaked within 1 or 2 min and ended within 6 min. AVP and OT also elicited a sustained plateau phase response that lasted for as long as the cells were exposed to the secretagogue, but AII did not. Removal of Ca2+e diminished the initial spike phase by 30-50%, but depletion of Ca2+i virtually abolished it. In contrast, the sustained phase of the response to AVP and OT was abolished by removal of Ca2+e. The effect of dioctanoylglycerol, which elicits a sustained progressive increase in ACTH release, but no initial spike phase, was also greatly inhibited by Ca2+e removal; no greater effect was observed when Ca2+i was depleted. Blockade of L-type voltage-sensitive Ca2+ channels with nimodipine, a dihydropyridine drug, had the same effect as Ca2+e removal on both the initial spike and sustained plateau phases of the response to AVP. Inhibiting cAMP-dependent calmodulin with penfluridol had no effect on the initial spike phase, but reduced the sustained plateau phase of the response to AVP. Removal of Ca2+e or depletion of Ca2+i did not abolish the synergistic ACTH secretory response to the combination of AVP and CRF.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

Intractable diabetic ketoacidosis due to insulin antibody--response to steroid therapy.

To examine the effect of steroid therapy on insulin antibody titer in insulin-dependent diabetes mellitus, we studied a 58 year-old gentleman with recurrent diabetic ketoacidosis. No any overt precipitating factors could be accounted for, except limited pancreatic beta cell reserve and high titers of anti insulin antibodies. Despite the persistence of high titers of plasma antiinsulin antibodies, the clinical manifestations of diabetic ketoacidosis improved greatly by the administration of steroid. Nevertheless, the patient still showed the great excursion of plasma glucose concentration.

Diabetes Mellitus, Type 1↗
PubMed1990

Coexisting hyperthyroidism and hyperparathyroidism: two cases report.

To examine the biochemical changes in coexisting hyperthyroidism and hyperparathyroidism, we have studied two female cases in our medical center. Both patients received biochemistry study, thyroid function test, thyroid autoantibody determination, parathyroid function tests and thyroid scan. They all had increased thyroid function. The concentration of parathyroid hormone was found to elevate in both cases. After thyroid function turned normal, hypercalcemia was still present. Both patients underwent neck operation. Parathyroid adenoma was found in both cases. The pictures of thyroid pathology showed diffuse hyperplasia in one case and lymphocytic thyroiditis in the other case.

Adenoma↗
PubMed1989

Insulin secretion and sensitivity in hyperthyroidism.

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.

Administration, Oral↗
PubMed1987

Modulatory effects of corticotropin-releasing factor on the delayed corticosteroid feedback in humans: implications of feedback sites.

We recently demonstrated the presence of a delayed phase of glucocorticoid feedback on nonstress-induced ACTH secretion in normal volunteers. In this study, we investigate the effects of corticotropin-releasing factor (CRF) on that delayed feedback pathway with an attempt to determine the sites on which glucocorticoid exerts its delayed feedback effects. Thirty normal subjects were subjected to study and each subject received a single midnight dosage of 30 mg/kg BW metyrapone before each test. The whole experiment was divided into two studies. In study I, we found that ovine CRF (oCRF) 1 microgram/kg BW alone as an IV bolus injection caused an increase in the plasma ACTH level, which persisted for at least 120 minutes. Continuous infusion of cortisol 25 mg/h alone for two hours produced a significant decrease in the plasma ACTH level; this fall of ACTH began 30 minutes after the onset of cortisol administration. When IV bolus injection of oCRF 1 microgram/kg BW and the continuous infusion of cortisol 25 mg/h for two hours were both given, the plasma ACTH level increased firstly and then decreased 60 minutes after the onset of cortisol administration, progressing thereafter to the end of the study. Study II showed in those who received the IV bolus injection of human CRF (hCRF) 100 micrograms and the continuous infusion of cortisol 25 mg/h for two hours, the plasma ACTH level increased firstly and began to decline 45 minutes after the onset of cortisol administration, progressing thereafter to the end of the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Evidence for a delayed, integral, and proportional phase of glucocorticoid feedback on ACTH secretion in normal human volunteers.

To investigate the mechanisms responsible for glucocorticoid feedback on nonstress-induced ACTH secretion in normal subjects, 24 volunteer subjects (14 males and 10 females, 21 to 43 years) were divided into six groups in a randomized fashion and studied. Each subject received a single midnight dose of 30 mg/kg per body weight of metyrapone and then cortisol was administered according to different protocols in the next morning to provide extreme variations of the input signal. It was found that no obvious inhibition in plasma ACTH levels was shown during the first 15 min despite the fact that cortisol was given at rather larger doses and short time intervals. However, a significant suppression in plasma ACTH levels began to manifest approximately 30 min after cortisol administration in each study group and it became apparent that the degree of inhibition of ACTH level at 75 min correlated with the plasma cortisol concentrations at the same moment (r = 0.97, P less than 0.01) as well as with the dosage of cortisol during this time, whatever administered (r = 0.99, P less than 0.01). In summary, our data provided evidence for a delayed, proportional, and integral phase of glucocorticoid feedback on nonstress-induced ACTH secretion in normal human volunteers.

Adrenocorticotropic Hormone↗