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V S Fang

Publications and source records attributed to V S Fang.

At least 37 records · Page 2Linked to original sources
PubMed1993

A primary cell-culture system for physiological studies of adrenocortical function.

We used guinea-pig adrenal tissue to develop a primary culture, enriched with zona fasciculata (ZF) cells. In a continuous culture up to 2 weeks, the cells maintained the characteristic of glucocortical function by producing cortisol as the final steroidogenic product and secreting it into culture medium. When culture medium, which was replaced at 24-hr intervals, was assayed for cortisol, the basal steroidogenic function peaked on day 5 and then declined. In response to 24-hr treatment with the bioactive adrenocorticotropic hormones (ACTH) on day 4, production of cortisol was stimulated and prolonged, and also cells were morphologically hypertrophic. This in vitro system provides a convenient laboratory method which can be used for studying adrenocortical function under a possibly physiological condition.

Adrenal Cortex↗
PubMed1992

Recovery of responses to ovine corticotropin-releasing hormone after withdrawal of a short course of glucocorticoid.

To characterize the recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term glucocorticoid treatment, we examined the responses to ovine CRH (oCRH) before and after prednisolone administration. Eight normal male volunteers were studied before (control) and after administration of 25 mg prednisolone twice daily orally for 14 days. Data are mean +/- SEM. The ACTH basal level was suppressed 24 h after prednisolone withdrawal (1.7 +/- 0.4 pmol/L vs. control, 3.5 +/- 0.6, P less than 0.02), but the ACTH response to oCRH was not significantly different from control (peak 12.8 +/- 2.0 pmol/L vs. 13.5 +/- 12.1, respectively). Seventy-two h post prednisolone basal ACTH levels had recovered to pretreatment values. Cortisol levels, both basal and in response to oCRH, were significantly suppressed 24 h post prednisolone (P less than 0.001). By 72 h post prednisolone, both basal and oCRH-stimulated cortisol had recovered to pretreatment levels. Dehydroepiandrosterone (DHEA), both basal and stimulated, was significantly suppressed 24 h post prednisolone (P less than 0.001). In contrast to cortisol, basal and peak DHEA remained suppressed 72 h post prednisolone (basal DHEA 9.1 +/- 1.1 nmol/L, P less than 0.05 vs. control; peak DHEA 20.0 +/- 3.3 nmol/L, P less than 0.01 vs. control). When expressed as percent rise, however, the DHEA response to oCRH was not significantly different from control. DHEA sulfate (DHEAS) was significantly lower than control at both 24 and 72 h post prednisolone (1.8 +/- 0.3 and 3.3 +/- 0.4 mumol/L respectively; control 7.2 +/- 0.7 mumol/L; P less than 0.001). The ratio of basal DHEA to DHEAS was significantly higher than control 72 h post prednisolone, indicating that DHEAS was more profoundly suppressed than DHEA. We conclude that after a short course of prednisolone pituitary ACTH secretion is the first parameter of the hypothalamic-pituitary-adrenal axis to recover. Hypothalamic secretion of CRH recovers next, followed by recovery of cortisol secretion. Secretion of DHEA and DHEAS remain suppressed after recovery of cortisol. This suppression may be caused by inhibition of sulfokinase activity by glucocorticoid.

Adrenocorticotropic Hormone↗
PubMed1991

Radioimmunoassay of epidermal growth factor in human lenses at various stages of development of cataract.

By using a highly specific and sensitive homologous radioimmunoassay, we found that the content of epidermal growth factor (EGF) in the lateral one-third of whole cataractous human lenses (age range 45-85 yr) extracted at elective intracapsular lens surgery, varied from undetectable to 106.25 pg mg-1 water soluble protein (WSP) (mean +/- S.D. = 39.70 +/- 38.90). When the lenses were grouped according to the stage of the cataract, i.e. immature (n = 3), mature (n = 4), and hypermature (n = 3), the means +/- S.D. were 92.56 +/- 26.23, 23.89 +/- 7.71, and 7.92 +/- 2.00 pg mg-1 WSP, respectively. In ten age-matched whole 'normal' lenses that we removed within 2-12 hr after death, the values in EGF of the lateral one-third of the lenses ranged from 2.91 to 36.40 pg mg-1 WSP (19.39 +/- 13.65). No correlation between the age of the lenses and the content of EGF could be demonstrated at the 95% confidence interval for the cataractous and 'normal' lenses. The quantity of endogenous EGF correlated significantly (P less than 0.01) with the clinical stage of the cataract and is probably related to the mitotic activity of the equatorial proliferative zone. We discuss the importance of EGF in normal and cataractous lenses and postulate that EGF in the lens is endogenous in origin.

Aged↗
PubMed1991

Sleep deprivation in the rat: XIII. The effect of hypothyroidism on sleep deprivation symptoms.

Previous studies of rats subjected to total sleep deprivation by the disk-over-water method had shown a large increase in energy expenditure (EE) and an initial increase followed by a later decrease in body temperature (Tb). It had been proposed that the increase in Tb resulted from regulation toward a higher temperature or setpoint, that the later decline in Tb resulted from excessive heat loss, and that the increase in EE supported both of these thermoregulatory changes. To evaluate this proposed role of the increase in EE, we examined whether blunting the EE rise in sleep-deprived rats by making them hypothyroid attenuated and/or shortened the initial increase in Tb and accelerated the later decline in Tb. Rats made hypothyroid by propylthiouracil administration (TxD rats) were totally sleep deprived and compared to hypothyroid yoked control (TxC) rats and to previously studied, untreated, totally sleep-deprived (TSD) rats. Neither TxD nor TxC rats showed large increases in EE like those of TSD rats. TxD rats did not initially increase Tb, as TSD rats had. Presumably, TSD rats had been able to support an initially elevated Tb, in spite of excessive heat loss, by large increases in EE, although even these increases were eventually insufficient. TxD rats showed much earlier and greater declines in Tb than TxC and TSD rats, eventually becoming severely hypothermic. These results support the interpretation that the large increase in EE previously seen in TSD rats had been compensatory for deprivation-induced thermoregulatory deficits. TxD rats survived an average of 17.1 days, which was not significantly different from survival time in TSD rats. However, there were differences in mortal processes between the two groups. TxD rats died or were sacrificed after chronic, severe hypothermia without observable signs of other morbid pathology. TSD rats had not shown similarly low Tb until just prior to death, but had shown signs of severe pathology, including severely debilitated appearance, disheveled fur, and severe lesions on their tails and on the plantar surfaces of their paws. These signs were diminished or absent in TxD rats, possibly due to blunted EE, lower Tb, or other effects of hypothyroidism. Because the skin changes seen in TSD rats were minimal in TxD rats, they could not have been responsible for the excessive heat loss.

Adipose Tissue, Brown↗
PubMed1990

Sleep deprivation in the rat: XI. The effect of guanethidine-induced sympathetic blockade on the sleep deprivation syndrome.

In earlier studies, rats totally deprived of sleep by a disk-over-water apparatus (TSD rats) had shown an increase in energy expenditure (EE) that could not be explained by increased motor activity or the metabolic expense of wakefulness. Excessive activation of a calorigenic mediator was a possibility, and norepinephrine-mediated sympathetic activation was the most likely candidate, because plasma norepinephrine (NE) levels had risen sharply in TSD rats. To determine whether this activation was necessary for increased EE in sleep deprived rats, the peripheral sympathetic blocking agent guanethidine (GU) was administered to six sleep-deprived (GD) rats and their yoked control (GC) rats. GU attenuated the increase in NE previously seen in TSD rats, but the increase in EE was not attenuated. Apparently, NE-mediated sympathetic activation was not critical for increased EE in sleep-deprived rats. On the other hand, plasma epinephrine (EPI) levels were significantly increased in GD (but not in GC) rats above those previously seen in TSD rats, suggesting the substitution of one calorigenic mediator for another in response to an abnormally elevated need for EE. Temperature data suggest that increased need for EE could arise from an elevated temperature setpoint and an inability to retain body heat. GD (but not GC) rats also showed other effects previously seen in TSD rats, including debilitated appearance; severe ulcerative and hyperkeratotic lesions on the tails and plantar surfaces; initially increased and later decreased body temperature; decreased plasma thyroxine; increased triiodothyronine-thyroxine ratio; and eventual death. Evidently, NE-mediated sympathetic activation was not critical to any of these effects, although a role for catecholamines cannot be ruled out.

Animals↗
PubMed1989

Sleep deprivation in the rat: V. Energy use and mediation.

We investigated the use and possible mechanisms mediating the increased energy expenditure (EE) previously described for rats subjected to total or paradoxical sleep deprivation. Bomb calorimetry of wastes showed that during deprivation the efficiency of energy utilization was not reduced. Estimates of CO2 production by the doubly labelled water method of indirect calorimetry correlated with EE estimated from the caloric value of food, weight change, and wastes and confirmed an increase in EE during deprivation. Core temperatures decreased during the later stages of deprivation, suggesting the hypothesis that excessive heat loss may have required increased EE to protect body temperature. The increased EE could not be explained by the metabolic cost of increase wakefulness, water exposure, or motor activity; an increase in resting EE was indicated. The contribution of the hypothalamic-pituitary-adrenal axis, thyroid gland, and sympathoadrenal system to the mediation of the EE increases was evaluated by measuring the plasma levels of their hormones. Results appear to rule out the first as a mediator. Evidence for the other two was equivocal.

Adrenal Cortex Hormones↗
PubMed1989

Delirium and neuromuscular symptoms in an elderly man with isolated corticotroph-deficiency syndrome completely reversed with glucocorticoid replacement.

A 68-yr-old man had developed intractable vomiting soon after recovering from a flu-like illness. The use of Compazine as an antiemetic produced classic dystonic manifestations which resolved rapidly after discontinuation and treatment with Artane. However, he later developed a variety of neurobehavioral disturbances which led to his admission to the hospital. Extensive diagnostic procedures failed to identify any gastrointestinal or neurological causes. His condition unceasingly worsened until hypocortisolemia was serendipitously discovered, and all of his symptoms disappeared rapidly and completely with glucocorticoid replacement. Over the course of hospitalization, other than a single episode of orthostatic hypotension, the patient did not manifest any signs of adrenal insufficiency or endocrinopathy. Although detectable, his plasma ACTH level was markedly low in the presence of hypocortisolemia. His adrenal function was subnormal in the cortisol response to ACTH stimulation. His renin-angiotensin-aldosterone system and catecholamine levels were normal. He had normal pituitary responses to GnRH, TRH, and insulin, with rises in plasma levels of LH, FSH, TSH, PRL, and GH, but no stimulation of ACTH. Repeated CRH tests revealed no stimulation of ACTH and cortisol. No circulating anti-ACTH, antiadrenal, or antipituitary antibody was detected. We conclude that this elderly patient had a rare syndrome of selective corticotroph dysfunction which resulted in secondary adrenal failure and exacerbated his mental and neuromuscular abnormalities. To our knowledge, these symptoms, which clearly relate to hypocortisolism, have not been previously reported.

Adrenal Insufficiency↗
PubMed1989

Sleep deprivation in the rat: IX. Recovery.

Eight rats were subjected to total sleep deprivation, paradoxical sleep deprivation, or high amplitude sleep deprivation until they showed major deprivation-induced changes. Then they were allowed to sleep ad lib. Three rats that had shown the largest temperature declines died within two to six recovery days. During the first 15 days of ad lib sleep, surviving rats showed complete or almost complete reversal of the following deprivation-induced changes: debilitated appearance, lesions on the paws and tail, high energy expenditure, large decreases in peritoneal temperature, high plasma epinephrine and norepinephrine levels, and low thyroxine levels. The most prominent features of recovery sleep in all rats were immediate and large rebounds of paradoxical sleep to far above baseline levels, followed by lesser temporally extended rebounds. Rebounds of high amplitude non-rapid eye movement (NREM) sleep occurred only in some rats and were smaller and less immediate.

Adrenal Cortex Hormones↗
PubMed1988

Cortisol response to ACTH infusion in depressed patients: comparison with age-, sex-, and weight-matched normal subjects.

Adrenal responsiveness to Cosyntropin (synthetic ACTH) was investigated in five patients with major depression and five individually matched normal subjects. Three hours following suppression of endogenous ACTH secretion with dexamethasone (1 mg orally), the adrenal response to a 10-min infusion of Cosyntropin (0.05 micrograms/kg body weight) was monitored for 2 1/2 hr by plasma cortisol measured at 15-min intervals. The depressed patients had significantly higher baseline plasma cortisol, but not higher baseline ACTH, than the controls. During the 3-hr post-dexamethasone (and prior to Cosyntropin infusion), the depressed patients maintained significantly higher cortisol secretion, but not higher ACTH secretion, than the controls. After Cosyntropin infusion, there were no differences in ACTH and cortisol increases between the two groups. These findings stand in contrast to previous reports of enhanced adrenal responsiveness to the administration of much larger amounts of Cosyntropin in major depression.

Adrenocorticotropic Hormone↗
PubMed1988

Recovery from glucocorticoid inhibition of the responses to corticotrophin-releasing hormone.

We have characterized the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term prednisolone administration. Prednisolone was given in a dosage averaging 25 mg at 12 h intervals orally for up to 2 weeks to adult volunteers. Human corticotrophin releasing hormone (hCRH) tests were performed at 0901 h using a bolus injection of 1 microgram/kg before and 24-48 h after discontinuing the prednisolone. In the initial control study, hCRH stimulated a two-fold rise in plasma ACTH and a 30% rise in plasma cortisol within 30 min (ACTH rose from 18.5 +/- 4.5, SEM, pg/ml to 36.5 +/- 12.6 pg/ml and cortisol from 415 +/- 58 to 531 +/- 69 nmol/l in response to hCRH. One dose of prednisolone had no effect on the ACTH or cortisol response to hCRH administered 24 h later. Twenty-four hours after discontinuing a 1 week course of prednisolone, baseline plasma ACTH (3.9 +/- 0.6 pg/ml) and cortisol (146 +/- 17 nmol/l) were markedly suppressed, as was the cortisol response to hCRH (peak 198 +/- 22). However, the plasma ACTH response to hCRH was not significantly suppressed. Forty-eight hours after discontinuing prednisolone, the recovery of ACTH secretion was complete (baseline 10.9 +/- 4.2, peak 36.4 +/- 14.8 pg/ml), but the cortisol response to hCRH was still depressed (peak 294 +/- 66 nmol/l). Recovery from a 2 week course of prednisolone had similar characteristics except plasma cortisol was depressed more profoundly. Plasma dehydroepiandrosterone (DHA) during hCRH tests and dehydroepiandrosterone sulphate (DHAS) paralleled plasma cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose.

Peripheral plasma or serum concentrations of glucose, insulin, C-peptide, glucagon, and cortisol and insulin secretory rates (ISR) were determined at 15-min intervals in eight normal subjects during a constant iv infusion of 4.5 mg glucose/kg.min for a 24-h period. During each sampling interval, the secretory rate of insulin was calculated by deconvolution of the peripheral plasma C-peptide concentration using C-peptide kinetic parameters derived after bolus injections of C-peptide in individual subjects. Periodogram analysis of the individual glucose curves demonstrated a circadian rhythm in all subjects, with a major nocturnal acrophase occurring at an average clock time of 0228 h (range, 0045-0350 h). In five of the eight subjects, a minor acrophase occurred at an average time of 1774 h (range, 1530-2045 h). This diurnal variation in plasma glucose levels was not paralleled by a similar pattern in insulin secretion. Although glucose was infused at a constant rate, significant pulses were found in glucose, insulin, and C-peptide levels and ISR; the pulse durations of these parameters were 182 +/- 30 (+/- SE), 89 +/- 5, 100 +/- 8, and 85 +/- 5 min, respectively, and their periodicities were 208 +/- 33, 106 +/- 7, 114 +/- 10, and 106 +/- 7 min. The durations and frequencies for pulses of insulin, C-peptide, and ISR were not significantly different, whereas glucose pulses had a longer duration and were less frequent (P less than 0.05, by analysis of variance). On the average, 54 +/- 9% of the C-peptide pulses and 47 +/- 8% of the ISR pulses were concomitant with a pulse in glucose levels. Moreover, approximately half of the C-peptide and ISR pulses that were not concomitant with a glucose pulse occurred in synchrony with a shoulder on the up-stroke or down-stroke of glucose pulses. Analysis of glucagon and cortisol profiles revealed no significant associations with the insulin and glucose oscillations. In conclusion, during a constant glucose infusion in normal subjects, regular oscillations of insulin secretion occur at 80- to 120-min intervals. Their tight coupling with glucose oscillations and the lack of association with fluctuations of glucagon and cortisol suggest that these oscillations represent a dynamic property of the insulin-glucose feedback loop.

Adult↗
PubMed1986

Administration of low-dose estrogen rapidly and directly stimulates growth hormone production.

We tested the concept that estrogen directly stimulates growth hormone (GH) production by determining whether low-dose treatment with ethinyl estradiol increases the GH reserve, as assessed by levodopa administration, without inhibiting somatomedin-C (Sm-C) levels. Twenty-three prepubertal short normal children underwent levodopa tests before and after being treated with ethinyl estradiol. One bedtime dose of ethinyl estradiol (20 to 40 micrograms/sq m, n = 8) resulted in a significant increase in GH levels during levodopa testing, with no significant change in Sm-C levels (0.27 +/- 0.03 vs 0.36 +/- 0.1 units/mL). Two days of a comparable ethinyl estradiol dose (n = 12) raised the mean basal GH level (2.4 +/- 0.4 vs 9 +/- 3 ng/mL) and had a similar effect on peak GH response, without affecting the mean Sm-C level. Eighteen of the 23 patients responded (maximum GH level, greater than or equal to 7 ng/mL) to levodopa before estrogen; all 20 children who received ethinyl estradiol priming in a dose of 20 micrograms/sq m or more also responded. We conclude that low-dose estrogen therapy rapidly stimulates GH production without decreasing Sm-C plasma levels. These results support the concept that the estrogen effect is direct. This action may be important for the stimulation of growth by estrogen. This effect can be conveniently employed to enhance the specificity of the levodopa test for profound GH deficiency.

Adolescent↗
PubMed1985

The effect of dexamethasone on the 24-hour profiles of adrenocorticotropin and cortisol in Cushing's syndrome.

ACTH and cortisol are normally secreted episodically rather than continuously. This characteristic of episodic secretion is preserved in patients with Cushing's syndrome. To determine whether exogenous glucocorticoids modulate this pulsatility and to study its possible etiological implications, we obtained 24-h plasma cortisol profiles in seven patients with Cushing's syndrome (five Cushing's disease, one adrenal adenoma, and one bilateral adrenal cortical macronodular hyperplasia) before and during suppression with various doses of dexamethasone [low (0.5 mg, every 6 h), high (2 mg, every 6 h), and very high (4 mg, every 6 h)]. Simultaneous 24-h plasma ACTH profiles were obtained in two patients with Cushing's disease. Blood was drawn at 30-min intervals for 25 h. Individual profiles were analyzed to determine the 24-h mean level, the presence of a circadian component and its amplitude, and the number and magnitude of significant secretory pulses over the 24-h span. The concordance between significant ACTH and cortisol pulses also was quantified. Baseline values in patients were compared to those in seven normal subjects. Under basal conditions, the 24-h mean cortisol level was 3- to 4-fold higher than normal in all patients with Cushing's syndrome. In contrast, the basal 24-h mean ACTH level was normal in one, and slightly elevated in the other of the two patients with Cushing's disease in whom plasma ACTH concentrations were measured. However, in contrast to the normal subjects, all ACTH values were above 10 pg/ml even during the period of minimal secretion. Basal circadian variation in adrenocortical activity, albeit of reduced amplitude, was found in four of five patients with Cushing's disease; it was absent in the patient with adrenal adenoma. Low dose dexamethasone reduced the 24-h mean cortisol level and increased the amplitude of the circadian rhythm, unmasking a diurnal rhythm in the single patient with Cushing's disease in whom no significant circadian periodicity was present in the basal condition. This effect was further increased with the high dose of dexamethasone, which concomitantly reduced the number and increments of the secretory pulses. A lesser effect was found in the patient with bilateral nodular hyperplasia, and no effect was seen in the patient with adrenal adenoma. ACTH pulsatility, but not diurnal rhythm, also was dampened by dexamethasone. Reduction in the magnitude, but not the number, of ACTH secretory pulses by dexamethasone produced a reduced concordance ratio of ACTH with cortisol pulses of 0.39, compared to 0.64 in the basal state.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1985

Enhancement of adrenal cortisol secretion after intravenous high dose dexamethasone.

To assess the possible existence of a short loop feedback mechanism of direct glucocorticoid suppression on the adrenal glands, we performed a series of tests employing insulin hypoglycemia or ACTH infusions to obtain adrenal stimulation by ACTH levels that remained within the physiological range. Although the rapidity of glucocorticoid suppression of the pituitary thwarted efforts to use endogenous ACTH as a stimulus, we were able to mimic the stressed state by very low dose ACTH infusions (0.05 microgram/kg BW). No inhibition of cortisol secretion in response to ACTH infusions was detected in tests done after administration of dexamethasone compared to placebo [mean integrated response, 29.37 +/- 1.91 (+/- SE) vs. 29.12 +/- 1.12 microgram . h/dl, respectively]. Furthermore, when high doses of dexamethasone were administered iv, a small paradoxical increase in cortisol secretion was found (33.82 +/- 1.44 microgram . h/dl) without a difference in ACTH levels. These data do not support the concept of significant direct glucocorticoid inhibition of adrenal secretion. Non-ACTH factors that may enhance cortisol secretion in the presence of ACTH may exist.

Adrenal Cortex↗
PubMed1985

Physiological dosing of exogenous ACTH.

We evaluated the ACTH and cortisol responses to several doses of exogenous ACTH, and compared these values to the physiologic responses obtained in normal subjects undergoing insulin-induced hypoglycaemia. We determined that a cosyntrophin dose of 0.2 micrograms/kg body weight produced both ACTH and cortisol levels indistinguishable from the 'physiologic' stress-induced values. Since this dose is approximately 4 per cent of the standard 250 micrograms dose employed in tests of adrenal function, our findings suggest a need for caution in the interpretation of such tests.

Adrenocorticotropic Hormone↗
PubMed1984

Elevated beta-endorphin in cerebrospinal fluid after electrical brain stimulation: artifact of contrast infusion?

Beta-Endorphin-like immunoreactivity in cerebrospinal fluid was assayed in 11 patients receiving electrical stimulation of the brain for chronic pain. Immunoreactivity increased dramatically after contrast ventriculography prior to stimulation. No further elevations were observed after stimulation. The magnitude and time course of elevations were identical after placement of electrodes either in the thalamus or in the periventricular gray matter. These results suggest that previous findings of stimulation-induced elevation of beta-endorphin-like immunoreactivity in cerebrospinal fluid are attributable to an artifact of contrast ventriculography.

Adult↗