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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

At least 55 records · Page 3Linked to original sources
PubMed1994

Glucocorticoid responsive ACTH secreting bronchial carcinoid tumours contain high concentrations of glucocorticoid receptors.

Cushing's syndrome due to a bronchial ACTH secreting carcinoid tumour may be difficult to distinguish from a pituitary microadenoma (corticotrophinoma) causing Cushing's disease, since in both disorders ACTH secretion may be responsive to glucocorticoids. Why some bronchial carcinoid tumours are responsive is unknown but it could be because of co-secretion of corticotrophin releasing factor (CRF) and/or expression of glucocorticoid receptors. We report two patients with glucocorticoid responsive ACTH secreting bronchial carcinoid tumours, neither of whom produced or responded to CRF. Significant glucocorticoid receptor binding capacity (92 and 102 pmol/g protein), compared with control lung tissue, was found in extracts from both tumours. These findings suggest that corticotrophinoma-like responses to glucocorticoids observed in some ACTH secreting bronchial carcinoids result from expression of glucocorticoid receptors and are not necessarily related to the production of CRF.

ACTH Syndrome, Ectopic↗
PubMed1994

Plasma corticotrophin releasing hormone, vasopressin, ACTH and cortisol responses to acute myocardial infarction.

OBJECTIVES: We assessed the magnitude and duration of the response of hypothalamic-pituitary-adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and cortisol, during a prolonged medical stress. DESIGN: All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure. PATIENTS: Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily. MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll. RESULTS: At the start of the study, mean +/- SEM plasma AVP (27.9 +/- 4.6 pmol/l) was significantly (P < 0.001) raised above the mean for the reference range (1.82 +/- 0.09 pmol/l), and 12 patients had values > 50 pmol/l. Mean plasma cortisol (960 +/- 89.6 nmol/l) was also raised above the reference range mean (554 +/- 28 nmol/l, P < 0.001), as was mean plasma CRH (4.97 +/- 0.5 pmol/l, reference mean 1.52 +/- 0.09 pmol/l, P < 0.001). By contrast, mean ACTH (3.88 +/- 0.66 pmol/l) was significantly less than the reference mean (10.7 +/- 0.7 pmol/l, P < 0.001). During the 72-hour observation period there was a highly significant fall (P < 0.001) in plasma CRH, AVP and cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or cortisol (P < 0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or cortisol responses to placebo, captopril or enalapril were observed. CONCLUSIONS: Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1 AVP receptor antagonists may have a therapeutic application in limiting infarct size.

Adrenocorticotropic Hormone↗
PubMed1994

Short-term secretion patterns of corticotropin-releasing hormone, arginine vasopressin and ACTH as shown by intensive sampling of pituitary venous blood from horses.

To characterize the short-term ACTH secretion pattern and to investigate factors regulating it, pituitary venous (PV) blood was collected using our nonsurgical method from 8 unperturbed horses every 20 or 30 s for approximately 1 h. In all but 1 horse, sampling occurred during the broad circadian maximum in plasma cortisol concentrations. Concentrations of corticotropin-releasing hormone (CRH; n = 7 horses), arginine vasopressin (AVP), ACTH and cortisol were measured by radioimmunoassay. In all horses, CRH, AVP and ACTH secretion patterns appeared irregular in time and amplitude. The mean (+/- SEM) numbers of peaks per hour detected by the cluster program were 2.8 +/- 1.2, 10.1 +/- 1.9 and 10.2 +/- 1.4 for CRH, AVP and ACTH, respectively. However, when 2- and 5-min sampling frequencies were simulated by meaning consecutive values, significantly fewer peaks were detected in each hormone. There was no correlation between the prevailing cortisol concentration and peak frequencies of CRH, AVP or ACTH. Secretion patterns of ACTH and AVP were closely related in all horses as assessed by cross correlation analysis and coincidence of peaks, although the ratio between PV ACTH and AVP concentrations fluctuated markedly within each horse. In contrast, the relationship between CRH and ACTH secretion was variable. Bivariate spectral analysis showed only a modest degree of underlying periodicity in CRH, AVP and ACTH secretion during the very short term studied. Nevertheless, distinct peaks exceeding the 95% confidence limits of white noise were observed at periods between 2 and 30 min in 5 of 7 CRH, 6 of 8 AVP and 5 of 8 ACTH spectra. Furthermore, the slope of the regression line through each spectrum did not become indistinguishable from zero, i.e. the flat white noise continuum, until mean (+/- SEM) periods of 2.6 +/- 0.8, 1.6 +/- 0.2, and 2.0 +/- 0.2 min, for CRH, AVP and ACTH spectra, respectively. At the ACTH spectral maximum, the coherence coefficient, which is analogous to the squared correlation coefficient, exceeded 0.5 in comparisons of all ACTH and AVP spectra and of 5 of 7 ACTH and CRH spectra.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

The effects of corticotrophin-releasing hormone, arginine vasopressin and their antagonists on ACTH release from perifused horse anterior pituitary cells.

Antagonists are useful for probing hormone action and receptor characteristics. In this study we have investigated the inhibitory effects of analogues of arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) on stimulated release of immunoreactive ACTH from perifused equine anterior pituitary cells in vitro. Our aims were to gain some insight into the characteristics of the CRH and AVP receptors of the horse pituitary and to establish whether the response induced by AVP and CRH together could be blocked by combining antagonists. Experimental design included 5-min pulses of AVP (12.5 nmol/l), CRH (0.3 nmol/l) or CRH plus AVP given every 40 min alternately with pulses of secretagogue(s) plus appropriate antagonist(s). The effect of combined antagonists on the response to lower secretagogue concentrations (CRH, 0.03 nmol/l plus AVP, 2.5 nmol/l) was also tested. Response in the presence of an antagonist was compared with the mean response to secretagogue in the immediately preceding and following pulse and was expressed as per cent expected ACTH. The ACTH response to AVP was inhibited over the dose range 0.4-50 mumol/l by Phaa-D-Tyr(Et)2Lys6Arg3VP (P < 0.002; ANOVA) and by d(CH2)5[Tyr(Me)2]AVP (P < 0.001). Suppression of the expected ACTH response to AVP by these two antagonists was most effectively achieved by antagonist concentrations of 10 mumol/l (to 28 +/- 2.1%) and 25 mumol/l (to 22 +/- 5.1%) respectively. Inhibition was not improved by preinfusion compared with a bolus pulse. Aaa-D-Try(Et)2Val4Abu6Arg8.9VP and the non-peptide antagonist OPC-21268 had no inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Horse plasma corticotrophin-releasing hormone (CRH): characterisation and lack of a late gestational rise or a plasma CRH-binding protein.

Immunoreactive corticotrophin-releasing hormone (irCRH) was present in methanolic extracts of equine peripheral blood and showed no elevation in maternal peripheral serum in late gestation (0.54 +/- 0.25 pmol/l; mean +/- S.D.) compared with control horses (0.41 +/- 0.15 pmol/l). The irCRH of methanolic extracts of pituitary venous plasma had a similar elution position following reverse-phase HPLC to synthetic human CRH(1-41) and to irCRH released from horse stalk-median eminence tissue incubated in vitro. Gel chromatographic studies showed no evidence for a plasma CRH-binding protein (CRHBP) analogous to that found in human plasma in either peripheral blood from normal or pregnant horses or in pituitary venous plasma sampled from a cannulated horse. CRH-binding activity was detectable in peripheral plasma from one horse, however the molecular size of this was indicative of a gamma-globulin rather than the 37 kDa CRHBP. These studies suggest that, unlike in the human, CRH does not rise to high values in late gestation nor circulate in a bound form in equine plasma.

Animals↗
PubMed1993

Metyrapone induced increase in plasma corticotropin is not associated with changes in peripheral venous arginine vasopressin or corticotropin releasing factor.

The responses of the "stress hormones" cortisol, 11-deoxycortisol, ACTH, vasopressin (AVP), and corticotropin releasing factor (CRF) were studied in 6 normal males in response to acute cortisol deficiency induced by the 11-beta-hydroxylase inhibitor, metyrapone. A 750 mg dose was administered orally at 08:00 h on day 1 and at 4 hourly intervals over a 24-h period. A 20 mg tablet of hydrocortisone or placebo was then given at 08:00 h on day 2, according to a randomized cross-over design. Each subject was restudied after an interval of at least one month. Blood samples were taken for all hormones at 08:00 h on day 1 and at 04:00 h on day 2. Thereafter ACTH and AVP were sampled at 10-min intervals, CRF at 20-min intervals, and cortisol and 11-deoxycortisol at hourly intervals until 12:00 h on day 2. Cortisol (mean +/- SE) fell from 628 +/- 218 nmol/l at 08:00 h (day 1) to a minimum of 230 +/- 78 nmol/l at 05:00 h on day 2. Plasma 11-deoxycortisol rose from 14.0 +/- 0.8 nmol/l to a maximum of 622 +/- 36 nmol/l and plasma ACTH rose from 8.71 +/- 1.64 pmol/l to a maximum of 166.2 +/- 57.5 pmol/l. Diurnal rhythmicity of plasma ACTH was maintained. There was no detectable change in plasma levels of AVP or CRF from baseline (AVP 2.5 +/- 0.8 pmol/l, CRF 3.4 +/- 0.5 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Atrial natriuretic factor reduces vasopressin and angiotensin II but not the ACTH response to acute hypoglycaemic stress in normal men.

OBJECTIVE: We determined the effects of physiological (non-hypotensive) increments of plasma atrial natriuretic factor (ANF) on the vasopressin and hypothalamic-pituitary-adrenal response to insulin induced hypoglycaemia. DESIGN: Single blind, placebo controlled, randomized study of the effect of vehicle alone or ANF (2.5 pmol/kg/min for 120 minutes) commencing 30 minutes before bolus administration of insulin (0.15 U/kg body weight). RESULTS: ANF infusion raised venous plasma ANF levels four to five-fold (mean level 32 +/- 0.3 pmol/l at time of insulin injection) without affecting resting blood pressure or heart rate. After insulin, the fall in plasma glucose and rise in plasma adrenaline and noradrenaline were similar in both studies. In contrast, the responses in plasma arginine vasopressin (P < 0.02) and in plasma angiotensin II (P < 0.05) were inhibited by ANF. Plasma corticotrophin releasing factor, ACTH and cortisol responses to hypoglycaemic stress did not differ significantly in the presence and absence of ANF. CONCLUSION: We conclude that four to five-fold acute increase in plasma ANF, while attenuating vasopressin and angiotensin II responses to hypoglycaemia, does not inhibit the hypothalamic, pituitary and adrenal responses or inhibit sympathetic nervous activation in normal men.

Acute Disease↗
PubMed1993

The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy.

OBJECTIVES: We compared the responses of the stress hormones, cortisol, ACTH, vasopressin (AVP), corticotrophin releasing hormone (CRH) and catecholamines to elective conventional and laparoscopic cholecystectomy. DESIGN: A right upper quadrant transverse incision was used for conventional cholecystectomy, and four 1-2-cm incisions for the laparoscopic procedure (for insertion of surgical instruments, diathermy, fibreoptic telescope and light source, and carbon dioxide insufflation). Blood was sampled immediately prior to premedication (temazepam), after induction of anaesthesia (fentanyl and thiopentone) and at 10-minute intervals until the end of the procedure (N2O maintenance, vecuronium relaxation). A blood sample was taken after reversal, and then at 10-minute intervals for 50 minutes. Plasma sodium and blood pressure were measured at similar intervals. Results are expressed as mean +/- standard error. PATIENTS: Twelve patients were studied (six in each group). MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and catecholamines by HPLC. RESULTS: The mean premedication hormone values for the conventional and laparoscopic procedures did not increase significantly after induction of anaesthesia. Within 10 minutes of the first incision, however, there was a marked concordant rise in mean plasma ACTH and AVP levels for both procedures (conventional: ACTH, from a premedication value of 10.2 +/- 1.7 to 80.1 +/- 14.3 pmol/l, AVP from 1.2 +/- 0.4 to 117 +/- 24 pmol/l, P < 0.01 for both hormones; laparoscopic: ACTH from 5.8 +/- 2.6 to 55.1 +/- 26.0 pmol/l, AVP from 1.6 +/- 0.11 to 49.2 +/- 27.09 pmol/l). At the end of both types of operation mean levels of ACTH and AVP were still elevated, although the ACTH: AVP ratio had increased. Greater variability in ACTH and AVP responses was seen in the laparoscopic than in the conventional procedure, three patients showing a relatively small response to surgery. Total secretion of ACTH during both types of surgery was not significantly less both during (P < 0.05), and after (P < 0.01) laparoscopic surgery. For both procedures, the timing of AVP and ACTH peaks was significantly related (P < 0.002). A small but significant rise in CRH was observed 30 minutes after the start of surgery for both procedures P < 0.05). The timing of CRH and ACTH peaks was unrelated. The maximum mean plasma cortisol level for the conventional procedure (1268 +/- 147 nmol/l) was reached 20 minutes after reversal of anaesthesia and remained at this level until the end of sampling. The cortisol response was comparable during the laparoscopic procedure but was beginning to fall at 60 minutes post-operatively. Plasma adrenaline responses to the two types of surgery were not significantly different, but the plasma total noradrenaline response to laparoscopic surgery as indicated by the response area during the first 20 minutes was significantly increased (P < 0.02). Plasma sodium, renin activity and initial systolic blood pressure fall were not significantly different during the two procedures. CONCLUSIONS: For both procedures, the peak of ACTH secretion after incision is likely to be AVP dependent, and the timing of peak levels of these two hormones was significantly related. Subsequent ACTH secretion may be the result of an interaction between AVP and CRH. Laparoscopic cholecystectomy results in a smaller AVP rise than does the conventional procedure, and plasma AVP falls more rapidly post-operatively. During the period of observation, ACTH, CRH, cortisol and adrenaline responses were not significantly lessened by the laparoscopic approach, but there was a significant increase in the noradrenaline response. Stress hormone monitoring may assist further improvements in surgical technique.

Adrenocorticotropic Hormone↗
PubMed1993

The acute effect of lowering plasma cortisol on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin as revealed by intensive sampling of pituitary venous blood in the normal horse.

The effect of an acute fall in plasma cortisol on the secretion of CRH, arginine vasopressin (AVP), and ACTH was studied using our nonsurgical technique for collecting pituitary venous (PV) blood from horses. PV blood from six mares was collected continuously and divided into 30-sec segments for 0.5 h before and during a 3-h infusion of metyrapone, an 11-beta-hydroxylase inhibitor. During treatment, plasma cortisol fell (P < 0.01) to a mean nadir of 15% of pretreatment levels, and 11-deoxy-cortisol rose (P < 0.02). Three mares became mildly agitated during treatment. Mean PV concentrations of CRH (P < 0.025), AVP (P < 0.05), and ACTH (P < 0.005) were higher during the second hour of treatment than before. For AVP (P < 0.05) and ACTH (P < 0.01), the amount secreted in peaks detected by CLUSTER analysis increased during treatment, whereas peak frequency did not. Responses, particularly in CRH and AVP, tended to be amplified during agitation. Increases in CRH, AVP, and ACTH secretion commenced when cortisol had fallen to 50-59% of the initial value (P < 0.005 for each). By contrast, the cortisol concentration at this point varied 3-fold among mares. The ratio between PV concentrations of ACTH and CRH, which was used as an index of pituitary responsiveness to endogenous CRH, also rose (P < 0.005) as cortisol fell. The increase in this ratio preceded any significant change in CRH secretion and was maintained to the end of the experiment. We suggest that the initial response to falling cortisol in the horse is at the pituitary, via increased responsiveness to CRH. If cortisol continues to fall, AVP and then CRH secretion are stimulated. However, the magnitude of the hypothalamic response to hypocortisolemia may be augmented by concurrent stress. Last, the hypothalamo-pituitary-adrenal axis of the horse appears to monitor changes in plasma cortisol and not concentrations, at least in the short term.

Adrenocorticotropic Hormone↗
PubMed1993

Acutely raised corticotropin levels in Addison's disease are not associated with increased plasma arginine vasopressin and corticotropin-releasing factor concentrations in peripheral plasma.

Using an intensive sampling protocol we have examined the associations of peripheral plasma arginine vasopressin (AVP) and CRF with nocturnal ACTH hypersecretion in patients with Addison's disease. Six subjects were studied during a phase of cortisol withdrawal (36 h) and after cortisol substitution, and the findings were compared to those in four normal control subjects. The pulse properties of ACTH hypersecretion at a 10-min sampling interval have also been examined in these settings, using Cluster analysis. In the period before cortisol replacement, the Addison's patients showed significantly greater ACTH peak maxima and peak increments than the control subjects [107 +/- 44 vs. 5.5 +/- 1.3 pmol/L (P = 0.009) and 57 +/- 23 pmol/L vs. 3.7 +/- 0.9 pmol/L (P < 0.05), respectively]. After cortisol replacement, a significant decrease in mean peak increment (57 +/- 24 vs. 15 +/- 5 pmol/L; P = 0.021) occurred. The mean interpulse intervals did not differ significantly between the Addison's and control subjects (59 +/- 5 vs. 59 +/- 4 min overall). Although not significant, the trend for the pulse interval to increase after oral cortisol (60 +/- 6 vs. 72 +/- 9 min) is probably a result of the extremely low levels of ACTH after oral cortisol administration, making peak detection difficult. Despite the ACTH hypersecretion in the Addison's subjects, plasma AVP levels were at no time different from those in the control subjects. Plasma CRF levels tended to be lower in the Addison's patients than in the control subjects. We conclude that in states of cortisol deficiency, such as Addison's disease, ACTH hypersecretion results from enhanced ACTH peak amplitude, without a change in the frequency of ACTH secretory pulses. The marked increase in plasma ACTH that follows acute cortisol deprivation is independent of detectable changes in peripheral plasma levels of CRF or AVP.

Addison Disease↗
PubMed1993

Factors affecting ACTH release from perifused equine anterior pituitary cells.

The multifactorial control of ACTH is well established. We wished to establish and characterize an in-vitro perifusion system, using equine anterior pituitary cells and physiological concentrations of secretagogues, to investigate factors which affect the dynamics of ACTH secretion. Anterior pituitary tissue was divided for dispersion into cells with collagenase, trypsin or dispase, or by mechanical dispersion. After dispersal followed by 18-h incubation, cells were perifused and the ACTH response to 10-min pulses of arginine vasopressin (AVP; 100 nmol/l), corticotrophin-releasing hormone (CRH; 0.01 nmol/l), and AVP (100 nmol/l) plus CRH (0.01 nmol/l) determined. ACTH responses to these secretagogues were lower (P < 0.05) in cells prepared using the enzymes dispase and trypsin than with the enzyme collagenase. Cells prepared by mechanical methods were not responsive. Collagenase-prepared cells were used in subsequent experiments. In dose-response studies (10-min pulse length), a steep CRH-ACTH dose-response curve was obtained with the minimum effective concentration of CRH between 0.001 and 0.01 nmol/l, and a maximum effective concentration of 1.0 nmol/l. A less steep AVP-ACTH dose-response curve was obtained with a minimum effective concentration of AVP between 0.5 and 5 nmol/l, and no plateau in response up to 5000 nmol AVP/l. Increasing the incubation time between cell preparation and stimulation with AVP from 18 h to 90 h significantly (P < 0.01) increased the ACTH response. Repeated stimulation by AVP (100 nmol/l) or CRH (0.01 nmol/l) (5-min pulses every 30 min for 23 pulses) produced ACTH responses which decreased in an approximately exponential curve with time. When AVP and CRH were given at physiological concentrations, pulse lengths and pulse frequency, the ACTH response to repeated 1-min pulses of AVP, measured as height above basal secretion, was potentiated by the addition of CRH (1, 2.5, 5, 10 and 20 pmol/l) as a constant perifusion at all AVP concentrations tested (1 nmol AVP/l, P < 0.02; 10 nmol AVP/l, P < 0.0005; 25 nmol AVP/l, P < 0.0005). During the 1-min AVP pulse, the AVP concentration at the level of the cells was 30% of the expected concentration. Potentiation was increased both by increasing AVP concentration (P < 0.00005) and by increasing CRH concentration (P < 0.00005) up to 5 pmol CRH/l. The ACTH height response to repeated AVP stimulation significantly (P = 0.034) decreased with time, independent of CRH and AVP concentration. There was a significant (P = 0.014) decrease in ACTH response to CRH infusion with time, independent of CRH concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

The effect of cortisol on the secretion of ACTH by anterior pituitary cells of the horse in culture.

Perifused equine anterior pituitary cells were used to investigate the effect of cortisol on the ACTH response to pulses of corticotrophin-releasing hormone (CRH; 0.01 nmol/l) and arginine vasopressin (AVP; 100 nmol/l), given for 5 min every 30 min for 690 min and ACTH measured in 5-min fractions. At the fourth pulse of secretagogue (0 min), a constant perifusion with cortisol began (0 nmol/l (control), 100, 200, 500, 5000 and 50,000 nmol/l) and continued until the ninth pulse (150 min). For each pulse of secretagogue, the amount of ACTH (pmol) secreted in response to each pulse (ACTH response area), the highest concentration of ACTH (microgram/l) measured after each pulse (peak height) and the mean ACTH in the three prepulse fractions (ACTH baseline) were determined. Data from control columns in each experiment were fitted by least squares to an exponential function to produce a mean control value for each end-point; results in all columns were expressed as a percentage of the mean control values. The addition of cortisol had a highly significant negative effect on ACTH response area, peak height and baseline at all times from +30 to +240 min (columns given cortisol compared with the mean of control column values by t-test). Analysis of variance of the data showed that the higher the cortisol concentration, the quicker the ACTH response area (P = 0.0072) and peak height (P = 0.002) decreased to < 50% of mean control, and the greater the maximum percentage change (suppression) in ACTH response area (P < 0.0001) and peak height (P < 0.0001). The maximum percentage change (suppression) in baseline was independent of cortisol concentration. At +30 min after the start of cortisol perifusion, the ACTH response area in CRH columns was significantly lower than in AVP columns (P = 0.0088), and remained lower 90 min after the end of perifusion (P = 0.0084) but the maximum percentage change (suppression) was not different between secretagogues. ACTH peak height was significantly (P < 0.0268) lower in CRH than in AVP columns (from +30 min until 180 min after the end of cortisol perifusion) and the maximum percentage change (suppression) was also greater (P = 0.0011) in CRH columns. This study shows the effect of different concentrations of cortisol on CRH- and AVP-induced ACTH secretion by equine anterior pituitary cells, and the time-course for ACTH responses to be inhibited by, and recover from, cortisol perifusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism.

Bone mineral density was studied before, and at one year after successful parathyroidectomy in six postmenopausal, three premenopausal females and one male with primary hyperparathyroidism. Dual photon absorptiometry was used to measure bone mineral density at the lumbar spine in all subjects, and at three areas of the hip in eight of the subjects. There was no significant change in bone mineral density at the lumbar spine after one year. Bone mineral density increased 7.4% at the femoral neck from 0.822 (SEM 0.053) g/cm2 to 0.895 (0.04) g/cm2; p less than 0.01, 8.7% at Wards triangle from 0.681 (0.065) g/cm2 to 0.745 (0.07) g/cm2; p less than 0.02. A 5.6% increase at the trochanteric region from 0.785 (0.053) g/cm2 to 0.803 (0.053) g/cm2 was not significant. These results indicate that significant increases occur in bone mineral density at the hip, but not at the lumbar spine at one year after parathyroidectomy in patients with primary hyperparathyroidism.

Adult↗
PubMed1992

Vasopressin, corticotrophin-releasing factor, and pituitary adrenal responses to acute cold stress in normal humans.

Acute cold stress is a consistent stimulus to ACTH secretion in rats yet inhibits arginine vasopressin (AVP) in both rats and humans. We have studied the interrelationships of AVP, corticotrophin-releasing factor, and atrial natriuretic factor (ANF) in the hypothalamo-pituitary-adrenal response to acute cold stress in normal humans. Six healthy male volunteers deprived of food and fluid for 6 h, and minimally clothed, were studied in the early afternoon. After a 30-min period at 22 C, subjects were exposed to cold stress (4 C for 30 min), followed by a 30-min equilibration period at 22 C. By the end of the period of cold exposure there was a fall in plasma volume of 7.8 +/- 1.4% (mean +/- SEM), a significant increase in both systolic blood pressure (P = 0.0001) and in plasma norepinephrine level (P = 0.0001), but no change in plasma epinephrine or in plasma ANF. Plasma AVP levels fell significantly (P less than 0.01) to reach a nadir at 5-10 min after cold exposure before returning to baseline levels. A significant fall in plasma cortisol levels occurred during the first 15 min of the baseline period and remained stable thereafter. No significant changes in plasma corticotrophin-releasing factor or ACTH occurred. These results suggest that cold inhibition of AVP release, presumably via afferent baroreceptor pathways, may act to reduce the response of the corticotrophs to a potentially noxious stimulus. Inhibition of AVP and/or ACTH during acute cold exposure are not dependent upon an increase in plasma ANF.

Acute Disease↗
PubMed1991

Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man.

OBJECTIVE: To evaluate the hypothalamo-pituitary-adrenal (HPA) response to both mild and intense exercise. DESIGN: Maximum oxygen consumption (VO2max.) was initially determined. Exercise to 20% (mild) and 90% (intense) VO2max. was undertaken in random order. Subjects were exercised over a 5-minute period to the required level of intensity, which was maintained for a further 10 minutes. SUBJECTS: Six trained male athletes. MEASUREMENTS: Brachial vein blood was sampled before and at 5-minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise. RESULTS: Maximum heart rate was 184 +/- 2 and 82 +/- 5 (mean +/- SEM) beats per minute at 90 and 20% VO2max. respectively. Plasma volume fell by 8.7 +/- 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and cortisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects. CONCLUSION: These results indicate that although significant HPA activation occurs during intense exercise, CRF does not appear to play a major role in mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important in this regard.

Adrenocorticotropic Hormone↗
PubMed1991

The effect of acute exercise on the secretion of corticotropin-releasing factor, arginine vasopressin, and adrenocorticotropin as measured in pituitary venous blood from the horse.

We have used the technique which we have developed for collecting pituitary venous blood from conscious, undisturbed horses to study the effect of acute vigorous exercise on the secretion of CRF, arginine vasopressin (AVP) and ACTH. Pituitary venous (pit) blood was collected every 1-5 min from nine trained racehorses at rest in the stable. The horses then trotted quietly for 10 min, after which they galloped as fast as possible for 4-6 min, before returning to the stable where sampling continued. In Exp 1 (n = 5) no blood samples were taken during exercise, whereas in Exp 2 (n = 4), pit blood was collected every 30 sec during exercise. Immediately after exercise, significant elevations in heart rate (P less than 0.001), body temperature (P less than 0.01) and hematocrit (P less than 0.001) were observed as compared with preexercise values. Jugular cortisol levels were higher after exercise (301.9 +/- 35.2 nmol/liter; mean +/- SEM) than before (187.3 +/- 34.8; P less than 0.01; n = 9). Likewise, jugular AVP levels increased with exercise (before, 0.65 +/- 0.11 pmol/liter; after 3.2 +/- 0.6; P less than 0.01; n = 6), whereas jugular CRF was not altered by exercise (before, 0.38 +/- 0.08 pmol/liter; after, 0.93 +/- 0.31; n = 6; NS). In Exp 1, no significant changes in pit ACTH, AVP, or CRF were observed after exercise. However in Exp 2 when pit blood was sampled during exercise all horses showed an immediate and dramatic rise in ACTH (P less than 0.01) and AVP (P less than 0.005) secretion which peaked during galloping with mean fractional changes above resting levels of 23.6 +/- 9.9 for ACTH and 51.7 +/- 24.0 for AVP. After exercise pit AVP levels were not different from resting, whereas ACTH remained elevated (11.4 +/- 6.9-fold above resting levels). By contrast, pit CRF levels were not altered by exercise. In both experiments together, pit AVP and ACTH concentrations were correlated in eight of the nine horses, whereas pit CRF and ACTH concentrations were positively correlated in only one of seven horses. We conclude that acute exercise causes a transient increase in ACTH secretion which occurs synchronously with an increase in AVP secretion. CRF does not appear to play a major role in mediating the initial ACTH response to exercise.

Adrenocorticotropic Hormone↗
PubMed1991

In vitro and in vivo studies of equine prolactin secretion throughout the year.

In vitro, the prolactin response of perifused anterior pituitary cells of horses to thyrotrophin-releasing hormone (TRH) (0.1, 1.0, 10 and 100 nM), correlated significantly with hours of daylight (P less than 0.01). Baseline concentrations of prolactin also were significantly correlated with daylength (P less than 0.01). When response and baseline data were fitted by nonlinear least squares to a cosine function, the circannual phase was -0.06072 (+/- 0.02170) and -0.05560 (+/- 0.0255), respectively, which are not significantly different from that of daylength. In vivo, prolactin secretion was measured in jugular plasma and pituitary venous effluent. Prolactin secretion by the pituitary (20- to 30-sec samples) showed pulses of 2-7 min duration above a varying baseline. Jugular prolactin concentrations correlated significantly with daylength (P less than 0.01, n = 20). The fractional plasma clearance rate was 2.50 x 10(-2) and 3.31 x 10(-2)/min in 2 horses. Seasonal changes in prolactin secretion in vivo and in vitro may reflect the amount of prolactin available for release.

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