Biomedical subjects
Publications and source records attributed to E N Bowser.
Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB2) to Fischer rats (AgB1) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.
Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.
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This study evaluated the effect of somatostatin on immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) secretion in vivo in rats and monkeys and on iPTH secretion in vitro by normal bovine parathyroid tissue and by a human parathyroid adenoma. Somatostatin infusion promptly (within 0.5 h) suppressed both iPTH and iCT in both species studied in vivo, the suppression being progressive during the infusion period. In in vitro studies, somatostatin caused significant dose-related decreases in basal, low Ca-stimulated, and high Ca-suppressed PTH secretion from normal bovine parathyroid tissue and from basal and low Ca-stimulated PTH secretion from a human parathyroid adenoma. Therefore, somatostatin 1) suppresses both PTH and CT secretion in vivo; 2) acts directly on the parathyroid cell and presumably directly on the C-cell also; 3) acts upon normal and adenomatous parathyroid tissue; 4) suppresses basal, low Ca-stimulated and high Ca-suppressed PTH secretion; and 5) has a dose-related effect. The possible role of somatostatin in the physiological control of PTH and CT secretion (and therefore in Ca homeostasis), and in the pathogenesis of abnormalities of Ca homeostasis, requires further evaluation.
This study evaluated the effects of adrenergic agents on immunoreactive calcitonin (iCT) secretion in normal man, and compared the time course and magnitude of these adrenergic effects with those caused by modifying calcium (Ca) ion concentration. Ca infusion (15 mg Ca++/kg iv in 4 h) significantly increased plasma iCT within 1 h, reaching 140 +/- 8% of baseline at 4 h. EDTA (50 mg/kg iv in 2 h) significantly decreased plasma iCT within 15 min, with nadir value of 53 +/- 4.9% of baseline at 2 h. The beta-adrenergic agonist, isoproterenol, significantly increased plasma iCT with 5 min, reaching 136 +/- 5.9% of baseline at 30 min. The alpha-adrenergic antagonist, phentolamine, significantly increased iCT within 15 min, reaching 132 +/- 8.6% of baseline at 45 min. The beta-adrenergic antagonist, propranolol, significantly suppressed iCT with 15 min, reaching 51.8 +/-6.3% of baseline at 2 h. Therefore, 1) the adrenergic system (without induced change in serum Ca) can modify CT secretion to as great a degree as can change in Ca ion concentration induced by standard Ca and EDTA infusion tests and 2) even basal secretion of CT can be modified by adrenergic influences. These data strongly suggest 1) that the adrenergic system is an effective modifier of CT secretion and 2) that the adrenergic system, as well as Ca ion concentration, may play an improtant physiological role in control of CT secretion in man.
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We describe a radioimmunoassay for rhesus monkey and human immunoreactive calcitonin, in which a selected goat anti-human calcitonin antiserum, 131I-labeled synthetic human calcitonin tracer, and purified synthetic human calcitonin standards were used. The mean basal concentration of calcitonin in normal monkey plasma (254 microgram/liter) was not significantly different from that in normal human plasma (217 microgram/liter). The data indicate that the method is sensitive (lower limit of detection, 5 ng/liter), specific, accurate, and reproducible (coefficient of variation, 1-11% over a wide range of concentrations). Monkey calcitonin response to changes in plasma calcium concentration is similar to that in man, with significant correlation between calcium and calcitonin concentrations. Use of this radioimmunoassay for monkey and human calcitonin allows the monkey to be used in further studies of factors regulating secretion, function, and metabolism of calcitonin under various experimental conditions that would not be feasible in man.
A technique is described for glucose infusions and for frequent sampling of small quantities of blood in unrestrained and unanesthetized small laboratory animals. Under pentobarbital anesthesia, polyethylene catheters were implanted into the jugular vein and the aorta, and distal ends were exteriorized on the back of the neck of 250-gm. rats. Five to seven days following surgery the rats regained weight and were in a normal anabolic state, despite indwelling catheters. On the day of the intravenous glucose tolerance test (ivGTT), the exterior ends of the indwelling jugular and aortic catheters were connected to specially prepared extension catheters, through which a glucose pulse was given and frequent blood samples in small quantities were collected, respectively. During the entire procedure, the animals were resting quietly, unrestrained and unanesthetized. In another group of similar rats with indwelling catheters, ivGTT was performed after they were restrained in plastic restrainers. During the ivGTT, serum glucose levels were significantly higher in the restrained rats than those observed in the control rats. The mean glucose disposal rate (K) of 2.2 +/- 0.2 was significantly slower in restrained rats than the K of 3.0 +/- 0.3 in unrestrained rats. Following the glucose pulse, insulin secretion was significantly lower in restrained rats than that observed in the unrestrained rats. These observations emphasize the importance of controlling the modifying effects of mild stress on glucose tolerance and insulin secretion.
A radioimmunoassay for rhesus monkey and human immunoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that (a) the method is sensitive, specific, accurate and reproducible; (b) it is valid for both the rhesus monkey and the human; (c) the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; (d) monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and (e) the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human.
The effect of excessive growth hormone (GH) on parathyroid function in rats was evaluated in order to determine whether the GH-induced increase in serum calcium (Ca) may be mediated via stimulation of parathyroid hormone (PTH) secretion. Rats receiving injections of bovine GH 2 mg daily for 4 weeks showed a progressive significant increase in both serum Ca and immunoreactive PTH (iPTH) after the second week. Rats receiving daily injections of rat GH, 0.25 mg daily for 3 weeks, followed by 0.5 mg daily for 3 additional weeks, showed a significant increase in serum iPTH during administration of the higher dose, and also a significantly increased parathyroid gland weight and PTH content. The concomitant increase in serum Ca and iPTH suggest that GH stimulates the parathyroid glands to increase PTH secretion, which in turn causes an increase in serum Ca. The parathyroid response increases with the increase in dose and duration of GH stimulus. The data suggest that the hypercalcemia often observed in acromegaly may be due, at least in part, to GH-induced excessive secretory activity of the parathyroid glands.
In the rat, EDTA and isoproterenol stimulated PTH secretion, whereas high calcium and propranolol inhibited it. The stimulatory effects of EDTA and isoproterenol were still evident and unaltered in the presence of blocks induced by propranolol and high calcium, respectively. The findings suggest that: (i) both calcium and beta-adrenergic stimuli affect PTH secretion; and (ii) the two influences affect the PTH secretion by separate initial pathways.
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The role of adrenergic stimuli in the secretion of parathyroid hormone (PTH) in man was evaluated. Intradermal injections of isoproterenol, 0.15 mg, or epinephrine, 0.3 mg, caused significant prompt increases in serum PTH levels. These increases were not accompanied by any changes in serum calcium (Ca) during the period of observation. Phenylephrine, 1.5 mg, intradermally, did not cause any significant changes in serum PTH or serum Ca. Propranolol infusion alone significantly inhibited the basal secretion of PTH. This inhibition by propranolol was overcome by isoproterenol administration. The results indicate that 1) beta adrenergic agents increase PTH secretion whereas alpha adrenergic agents have no effect, 2) beta adrenergic stimuli probably play an important physiological role in basal PTH secretion in man.
Administration of aminophylline to intact rats did not cause a change in serum Ca, but did cause a significant increase in serum PTH. Administration of EDTA alone caused hypocalcemia, and a greater increase in PTH than that caused by aminophylline alone. Aminophylline plus EDTA given togeather caused no greater hypocalcemia, but a significantly greater increase in PTH than that by EDTA alone. Therefore, aminophylline increased PTH secretion when given alone, and also enhanced the PTH secretion stimulated by EDTA-induced hypocalcemia in vivo.