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PubMed1994

Relation of attenuated proestrous luteinizing hormone surges in middle-aged female rats to in vitro pituitary gonadotropin-releasing hormone responsiveness.

Prior to the cessation of regular cyclicity, middle-aged rats display pre-ovulatory luteinizing hormone (LH) surges of reduced magnitude. The present study was designed to identify whether middle-aged female rats with attenuated proestrous LH surges have alterations in pituitary responsiveness to gonadotropin-releasing hormone (GnRH). Young (4 months old) and middle-aged (10-12 months old) regularly cycling females were catheterized and sampled on proestrus to characterize their LH surge profiles. On the next proestrus (12.00 h), pituitaries were perifused individually and exposed to three pulses of GnRH (30 nmol/1). The patterns of the proestrous LH surges revealed that 12 of 22 middle-aged rats had attenuated surges (< 7 micrograms/l) while the remaining 10 middle-aged females had surges that were similar to those of young rats. Pituitaries perifused on the next proestrus showed similar basal LH release among the middle-aged and young females. However, the LH secretory rates following the second and third administration of GnRH, as well as the overall GnRH-stimulated LH secretory rates, were significantly decreased in middle-aged females with previously attenuated LH surges as compared to those from the young proestrous rats. In contrast, middle-aged rats with normal LH surges had pituitary LH responses that were no different from those of young females. These results indicate that a decrease in pituitary LH responsiveness to GnRH is only apparent in middle-aged rats that display attenuated proestrous LH surges.

Aging↗
PubMed1975

Quantification of carcinoembryonic antigen-like activities in normal, human gastrointestinal secretions.

The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.

Adult↗
PubMed1974

Characterization of the plasma lipoproteins of the genetically obese hyperlipoproteinemic Zucker fatty rat.

The plasma lipoproteins of the Zucker fatty rat were characterized with respect to lipid and apoprotein composition, and results were compared with those obtained from lean controls. Information on apoproteins was obtained from gel filtration experiments and electrophoresis on polyacrylamide gels. Very low density lipoproteins (VLDL) were increased several-fold in fatties, and 78% of their mass was triglycerides compared with 60% in the controls. Low density (LDL) and high density (HDL) lipoproteins were increased by a factor of 2, although their compositions were similar to those of the controls. Levels of apoVLDL, apoLDL, and apoHDL were five, two and two times higher, respectively, in the fatties, and the two most rapidly moving subunit peptides on polyacrylamide gels were disproportionately elevated in the apoproteins. The slower of these two bands was present in relatively greater amounts than the faster one in fatties. If the slower peptide is an activator of lipoprotein lipase, analogous to the comparable subunit peptides of human apolipoproteins, plasmas of fatties could contain up to 10 times more lipase activator activity than control plasma. This finding, and the fact that adipose tissue lipoprotein lipase activity of fatties was about 150% of controls, suggests that fatties have increased capacities for VLDL catabolism. We have previously shown that hepatic VLDL secretory rates are higher than normal in these animals. The increased capacity for catabolism may be a response to the altered secretory rates.

Adipose Tissue↗
PubMed1984

Apparent and intrinsic sensitivity to pentagastrin of acid and pepsin secretion in peptic ulcer.

The sensitivity to stimuli of gastric acid and pepsin secretion in duodenal and gastric ulcer was studied using a pentagastrin dose response that was analyzed by an exponential model. By this model, maximum secretory rate (Vmax), the dose of administered pentagastrin giving 50% of Vmax (D50), and the threshold equivalent dose responsible for basal secretory rate are calculated. Using only individual tests in which the data adequately fitted the model, we report on 171 subjects, 120 with duodenal ulcer, 22 with gastric ulcer, and 29 controls. Among the possible influences on secretion, sex and weight were significant, whereas age and activity or duration of ulcer disease were not. Men secreted more acid per kilogram body weight than women in each group, and men with duodenal ulcer secreted more acid and pepsin than normal men or those with gastric ulcer. Because basal secretion in men with duodenal ulcer was a higher proportion of maximum, D50 (the measure of apparent sensitivity) was 25% lower (p less than 0.01) in patients with duodenal ulcer than in controls; when examined by sex, men with duodenal ulcer had a lower D50 than women with duodenal ulcer, men with gastric ulcer, and male controls. D50 in all patients was very much lower for pepsin than for acid. Km, the dose that would be required to stimulate secretion to 50% of maximum if basal = 0 (intrinsic sensitivity), was not different between groups or sexes. Thus the difference in sensitivity between duodenal ulcer patients and controls was seen only in the apparent, and not in the intrinsic sensitivity indices; this was largely a phenomenon of males and could be explained by a higher ratio of basal to maximal secretion. Neither the observed increase of basal nor the maximal rates of acid and pepsin secretion in duodenal ulcer patients could be explained by an increased sensitivity to gastrin.

Adult↗
PubMed1994

VLDL production is decreased to a similar extent by acute portal vs. peripheral venous insulin.

Acute changes in very low-density lipoprotein (VLDL) triglyceride (TG) and VLDL apolipoprotein (apo) B production were examined in 11 healthy young males in response to insulin delivered either by the peripheral venous route or secreted directly by the pancreas. Steady rates of pancreatic insulin secretion were achieved for 5 h by a programmed intravenous tolbutamide infusion, while euglycemia was maintained with a dextrose infusion. Insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution, and, in a subsequent study, exogenous insulin was infused peripherally to match this pancreatic insulin secretory rate in each subject. Changes in VLDL TG and VLDL apo B production were determined semiquantitatively on each occasion by examining the change in slope of the specific activity (SA) of 3H-labeled triglyceride glycerol ([3H]TGG) and 131I-VLDL apo B vs. time curves, respectively, occurring with acute hyperinsulinemia. Plasma-free fatty acids (FFA), TG, apo B, and VLDL TG/VLDL apo B ratio decreased to a similar extent in both studies after the onset of hyperinsulinemia. VLDL TG production decreased significantly in both the tolbutamide (-47.1 +/- 7.3%, P < 0.002) and the exogenous insulin infusion study (-52.8 +/- 12.4%, P < 0.005). VLDL apo B production also decreased significantly in both studies (-58.9 +/- 7.5%, P = 0.0007 and -52.1 +/- 6.8%, P < 0.006, respectively), and there were no significant differences between studies. Tolbutamide was shown to have no independent effect on VLDL TG or VLDL apo B production in four insulin-deficient diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Insulin secretion induced by glucose and by stimulation of beta 2 -adrenoceptors in the rat. Different sensitivity to somatostatin.

The effects of somatostatin on insulin secretion stimulated by glucose or by the selective beta 2-adrenoceptor agonist terbutaline were studied in vivo in the anaesthetized rat. Infusion of low doses of glucose (5 mg/min) or terbutaline (2 microgram/min) caused slight stimulation of insulin secretion, whereas infusion of higher doses of glucose (12.5 mg/min) or terbutaline (200 microgram/min) yielded higher rates of insulin release. In both instances plasma insulin concentrations were of comparable magnitudes immediately prior to somatostatin infusion. Somatostatin (0.1 microgram/min) inhibited the insulin response to glucose and terbutaline, both at the low and high secretory rates. However, the inhibitory effect of somatostatin was much more pronounced on insulin release during glucose infusion than during infusion of terbutaline. Thus, at the high rate of insulin secretion somatostatin depressed plasma insulin by 46% during glucose and by 22% during terbutaline infusion. The results at the low rate insulin secretion were 66% and 48%, respectively. Both at high and low secretory rates somatostatin depressed plasma insulin levels more potently during glucose infusion than during terbutaline infusion (p less than 0.01 and P less than 0.05, respectively). Furthermore, the plasma insulin levels during inhibition by somatostatin following terbutaline stimulation stabilized after approximately 10 min of somatostatin infusion, whereas following glucose stimulation the insulin levels continued to decline. The results suggest that somatostatin inhibits insulin secretion via mechanisms that are more closely related to the insulin secretory pathway induced by glucose than to that induced by beta-adrenoceptor agonists.

Adrenergic beta-Agonists↗
PubMed1998

Effect of sensory neuropeptides on mucus secretion from cultured goblet cells.

BACKGROUND: Airway goblet cell secretion is under the control of capsaicin-sensitive sensory nerves. Administration of capsaicin or antidromic stimulation of nerves can stimulate goblet cell secretion and also induce plasma exudation and smooth muscle contraction via a release of neuropeptides from sensory nerve endings in the airway. This study was designed to explore whether the effect of capsaicin or neuropeptides on goblet cell secretion is direct or secondary to other airway responses. MATERIALS AND METHODS: We examined the effects of sensory neuropeptides including substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as capsaicin on cultured guinea pig tracheal goblet cells by measuring the rate of mucus discharge visually under a microscope and the release of 35SO4 radiolabeled mucin-like glycoconjugates. RESULTS: Goblet cells in culture spontaneously secreted intracellular granules at a mean rate of about 3 times/min. SP and NKA increased secretion in a dose-dependent manner. SP was more potent than NKA with maximum responses of 52% and 37% at 10(-8) M, respectively. Quantitative measurements of 35SO4 radiolabeled mucin-like glycoprotein (MLGP) secreted by goblet cells also revealed an increase (109.2%) in mucin secretion caused by SP (10(-8) M) compared with the vehicle control. Neither capsaicin nor NKB caused any significant change in the goblet cell secretory rate. The effects of SP on the secretory rate or release of radiolabeled mucin were not potentiated by an enkephalinase inhibitor, thiorphan (10(-5) M). CONCLUSION: Sensory neuropeptides SP and NKA directly stimulate goblet cell secretion, probably through the tachykinin receptor of the NK-1 subtype as suggested by a greater potency of SP. There was no direct effect of capsaicin on goblet cell secretion.

Animals↗
PubMed1988

Effects of calcium on synthesis and secretion of parathyroid hormone and secretory protein I.

Bovine parathyroid organoids were cultured for up to 3 wk in medium containing 1.4 or 1.8 mM calcium. Steady-state secretion of parathyroid hormone and secretory protein I was two- to fourfold greater at 1.4 mM. At the end of culture, organoids were incubated 3.5 h in 1 or 2 mM calcium to examine maximum and minimum acute secretory rates. Relative to organoids cultured at 1.8 mM calcium, culture at 1.4 mM induced a hypersecretory state, i.e., both the maximum and minimum acute secretory rates of organoids previously cultured at 1.4 mM calcium were up to threefold greater than those of organoids previously at 1.8 mM calcium. Proparathyroid hormone synthesis was up to 50% greater in organoids cultured at 1.4 mM calcium, whereas secretory protein I and total protein synthesis were unaltered. The results showed that parathyroid hypersecretion can be induced by chronic hypocalcemic conditions in vitro. We conclude that the secretory adaptation to chronic hypocalcemia in vitro involves alterations in both synthesis and degradation of parathyroid hormone.

Animals↗
PubMed2004

Salivary secretion assay for drug efficacy for cystic fibrosis in mice.

Computerized assays on cultured cells ex vivo have been used to screen thousands of compounds for their effectiveness in correcting the basic physiological defect in cystic fibrosis (CF). While a number of these compounds appear promising, their effectiveness will almost certainly need to be demonstrated in animals before therapeutic tests in humans will be possible. We show herein that the function of salivary secretion in the mouse model for CF could be used as a simple, easy and rapid in vivo assay for drug effects. We demonstrate that salivary secretory capacity stimulated with a beta-adrenergic agonist closely reflects the genotype of origin. Specifically, the mean maximal secretory rate of saliva in normal wild type (+/+) mice was about 1.5 times higher than that of the mean rate in heterozygote (+/-) mice and more than 50 times greater than in CF (-/-) mice. Total saliva secreted per stimulated period obeyed a similar phenotype-genotype segregation. The data indicate that salivary secretory rates in CF mice could be used to assay potential drugs for their effectiveness in correcting the secretory defect in cystic fibrosis.

Acetylcholine↗
PubMedDate not supplied

Role of gastric acid secretion and blood flow in the development of vagal stimulation induced gastric mucosal damage.

Vagal stimulation has been shown to result in the development of gastric mucosal erosions in the rat, although the mechanisms underlying the development of such erosions are not known. The effects of vagal stimulation on gastric acid secretion and mucosal blood flow were examined in urethane-anesthetized male Sprague-Dawley rats to determine whether changes in these factors correlate with the mucosal damage in response to vagal stimulation. Electrical stimulation (5 Hz, 5 V, 1 ms for 60 min) of afferent or efferent components of the vagi was not found to induce any significant increase in the mean acid secretory rate compared with control animals (p > 0.05). In contrast, stimulation of intact vagus nerves induced a significant increase in the mean acid secretory rate compared with control and efferent- and afferent-stimulated groups (p < 0.01). Measurement of gastric blood flow with laser-Doppler flowmetry demonstrated intact vagal stimulation to have no significant effect on gastric blood flow. These data suggest that such vagal stimulation induced increases in acid secretion in urethane-anesthetized animals may represent a part of the integrated physiological response to such stimulation which leads to the development of gastric mucosal erosions within 60 min. Pretreatment with antisecretory agents such as cimetidine and interleukin-1 beta significantly reduce the gastric mucosal injury compared with untreated animals (p < 0.05), emphasizing the important role of acid secretion in the development of vagal-induced gastric damage.

Animals↗
PubMed1998

Effect of cell density on hormonal secretion from human pituitary adenomas in vitro.

UNLABELLED: Cell density effects were investigated on tumorous hormonal secretion from 10 pituitary adenomas: 3 somatotrophinomas secreting GH and PRL; 7 gonadotrophinomas, 3 co-secreted both FSH and LH, all 7 secreted LH. Enzymatically dispersed tissue was plated out in 24-well plates at 5 x 10(5), 10(5), 5 x 10(4) and 10(4) cells/well in serum-free media. Media were collected weekly for 2 weeks. RESULTS: In 3 of 3 somatotrophinomas, GH and PRL secretion was higher (p < 0.05) at both week 1 and 2 from 10(4) cells/well, but similar at other cell densities. In all 3 gonadotrophinomas, the FSH secretory rate was highest at 5 x 10(5) cells/well which fell as cell density decreased. Conversely, in 7 of 7 gonadotrophinomas the LH secretory rate was highest at 10(4) cells/well (p < 0.01) which fell as cell density increased. CONCLUSION: These data suggest that paracrine factors may modulate tumorous GH, PRL, FSH and LH secretion, and show that FSH and LH secretion vary inversely as cell density increases.

Adenoma↗
PubMed1978

Pyrogenic renal hyperemia: the role of prostaglandins.

The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.

Animals↗
PubMed1987

Intracellular pH in the rat mandibular salivary gland: the role of Na-H and Cl-HCO3 antiports in secretion.

Intracellular pH (pHi) in the perfused rat mandibular gland was determined from the distribution of DMO (5,5-dimethyl-2,4-oxazolidinedione). In unstimulated glands, pHi averaged 7.12 +/- 0.02. Stimulation with a "standard" (submaximal) concentration (0.3 mumol/l) of acetylcholine (ACh) caused a fall in pHi to 6.81 +/- 0.06 over 60 min, but a maximal concentration (1.0 mumol/l) caused an initial rise in pHi to 7.60 +/- 0.02, followed by a fall to 7.45 +/- 0.02 over 60 min. After replacement of perfusate Cl with gluconate, the standard ACh concentration caused a rise in pHi to 7.50 +/- 0.02 followed by a fall to 7.27 +/- 0.04 after 60 min, concomitant with a 76% fall in secretory rate and a rise in salivary HCO3 concentration from 14 +/- 0.9 to 67 +/- 1.5 mmol/l. Furosemide (1 mmol/l) had a similar effect to gluconate replacement except that secretory rate fell only by 60%. Bumetanide (1 mmol/l), which inhibited secretion by 67%, did not cause pHi to rise following ACh stimulation but prevented the fall seen with ACh alone. Acetazolamide and methazolamide (1 mmol/l) had no effect on the salivary secretory response to ACh but they caused pHi to rise, respectively, to 7.20 +/- 0.03 and 7.43 +/- 0.02. Bumetanide and methazolamide together caused pHi to rise to 7.58 +/- 0.02 and reduced the secretory response to ACh by 91%. The disulfonic stilbene, SITS, caused pHi to rise to 7.26 +/- 0.03. Ouabain and amiloride both caused resting pHi to fall closer to equilibrium and largely abolished the gland's responsiveness to ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Luteinizing hormone (LH) secretory burst duration is independent from LH, prolactin, or gonadal steroid plasma levels in amenorrheic women.

The possible presence of LH pulsatile secretion has been studied in patients with hypothalamic amenorrhea [LH plasma levels, less than 3 (n = 35) or greater than 3 IU/L (n = 18)], amenorrhea associated with hyperandrogenemia (n = 31), or hyperprolactinemia (n = 10). Patients were sampled every 10 min for 4 h, and LH plasma concentrations were determined by the use of an immunofluorimetric assay. The program Detect was used for both pulse detection and data deconvolution, i.e. for instantaneous secretory rate computation, on LH time series. The presence of episodic LH secretion was observed in all patients, and LH pulse frequency ranged between 3.5 +/- 0.3 and 3.8 +/- 0.2 peaks/4 h among the four groups. LH pulse amplitude was significantly reduced in patients affected by hypothalamic amenorrhea with LH plasma levels lower than 3 IU/L (0.7 +/- 0.1 IU/L; P less than 0.01) and significantly increased in patients with hyperandrogenic amenorrhea (6.8 +/- 0.3 IU/L; P less than 0.01) compared to levels in the other groups under study. Instantaneous secretory rate computation permitted the optimal resolution of the secretory events and demonstrated that the duration of gonadotrope secretory bursts ranged from 22.8 +/- 1.4 to 26.8 +/- 2.3 min in amenorrheic patients and did not depend on LH, PRL, or sex steroid plasma levels. In conclusion, the present study shows the presence of significant LH pulsatile release in amenorrheic patients, suggesting that in amenorrheic, as in normally cycling, women the secretory bursts from the gonadotropes have the same duration, despite the plasma LH, PRL, or steroid hormone levels.

Adolescent↗
PubMed1985

Use of urinary C-peptide to estimate insulin secretion during starvation.

The usefulness of measurements of urinary C-peptide excretion in indirectly assessing integrated insulin secretion during starvation was studied in eight obese subjects during a 72-h fast. Blood and urine samples were collected at 12-h intervals for measurement of insulin and C-peptide immunoreactivity. After 60 h, serum insulin and plasma C-peptide levels declined 47% and 37%, respectively, and the values were highly correlated (r = 0.8; P less than 0.001). By 72 h, urinary C-peptide excretion had declined to 70% of the level in the first 12-h period. The urinary clearance of C-peptide was not altered by starvation. A highly significant correlation was found between urinary C-peptide and C-peptide secretory rate (P less than 0.001). The molar ratio of plasma C-peptide to insulin remained constant during the fasting period. These data indicate that basal insulin secretion can be added to the list of physiological conditions in which beta-cell secretion can be effectively evaluated by urinary C-peptide measurement.

Adult↗
PubMed1977

Regulation of the secretory cycles of mucous and serous cells in the human bronchial gland.

Studies of the human bronchial gland in organ culture have allowed us to elucidate some of the factors controlling the synthesis and secretion of bronchial mucus. The secretory cycles of mucous and serous cells appear to differ, the former alternately accumulating and discharging secretory material, while in the latter synthesis and discharge occur simultaneously. Parasympathomimetic agents increase the secretory rate of mucous and serous cells by stimulating discharge, but have no effect on the rate of precursor incorporation into intracellular glycoproteins. Glycoprotein synthesis inhibitors reduce the incorporation of precursors into intracellular macromolecules but do not reduce the rate of discharge of preformed glycoproteins. The rate of glycoprotein synthesis appears to be greater in mucus-secreting cells of hypertrophied glands than of normals. Ouabain reduces the incorporation of glucose and threonine, but not glucosamine, into mucous and serous cells but has no effect on the rate of discharge. In hypertrophied glands, ouabain--sensitive threonine, but not glucose, transport appears to be increased. Exposure of rats to tobacco smoke causes an increase in the size of tracheal and laryngeal glands and in the secretory rate of mucous cells. The anti-inflammatory agent, phenylmethyloxadiazole, prevents both tobacco smoke-induced effects, presumably by reducing the secretory activity of mucous cells.

Animals↗
PubMedDate not supplied

Renal handling of uric acid in man.

The uricosuric response to 80 mg of micronized Benzbromarone was employed to assess the renal tubular secretory site for uric acid in patients with primary gout. Since Benzbromarone selectively inhibits tubular reabsorption of secreted urate, the maximum uricosuria induced by this drug can be equated with the minimal secretory rate. Furthermore, a significant relationship was noted in normal controls between urate secretion and the plasma urate concentration (r = 0.956, p less than 0.005). Using the Benzbromarone response as a measure of tubular secretion, gouty patients with normal production hyperuricemia had a significantly lower secretory rate by comparison to patients with overproduction of uric acid. These data indicate that in patients with primary normal production hyperuricemia, the renal tubular defect is related to a decreased secretory response for a given plasma concentration of uric acid.

Adult↗
PubMed1997

Temporal relationships between pulsatile cortisol secretion and electroencephalographic activity during sleep in man.

A temporal link between slow wave sleep and low or decreasing cortisol release has been previously demonstrated. This relationship was re-evaluated in 15 healthy male subjects using spectral analysis of their sleep electroencephalogram (EEG). EEG activity in the delta, theta, alpha and beta bands was cross-correlated with cortisol secretory rates at 10-min intervals. For the period of pulsatile cortisol secretion, an inverse relationship was found with the delta band with an average cross-correlation coefficient of -0.505 (P < 0.0001). Variations in cortisol secretory rates coincided with or anticipated opposite variations in delta wave activity by 10 or 20 min. A significant positive correlation was found with theta activity, but alpha and beta bands did not elicit any systematic association with cortisol profiles. These results demonstrate a temporal association between cortisol secretory pulses and delta wave activity in man, suggesting the existence of a central control common to both variables.

Adult↗