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Biomedical subjects

G K Hargis

Publications and source records attributed to G K Hargis.

At least 37 records · Page 2Linked to original sources
PubMed1980

Mode of action of somatostatin in inhibiting parathyroid hormone secretion.

Effects of somatostatin on basal and low calcium-, isoproterenol- or dibutryl cyclic AMP (DBcAMP)-stimulated parathyroid hormone (PTH) secretion were evaluated in vitro with bovine parathyroid tissue. Low calcium, isoproterenol or DBcAMP alone significantly stimulated PTH secretion. Somatostatin 1 or 4 microgram/ml significantly inhibited these stimulated PTH secretions. Inhibition of isoproterenol-stimulated PTH secretion was more complete than was the inhibition of low calcium- or DBcAMP-stimulated secretion. The studies indicate that somatostatin inhibits PTH secretion by an action distal to cAMP generation. The more complete inhibition of isoproterenol-stimulated PTH secretion suggests that somatostatin may also have additional effects on or proximal to the formation of cyclic AMP.

Animals↗
PubMed1980

Altered maternal calcium homeostasis in diabetic pregnancy.

Twenty-one diabetic gravidas were studied with serial measurements of serum concentrations of total and ionized calcium, magnesium, phosphorus, albumin, and parathyroid hormone and plasma levels of calcitonin. Pregnant diabetics had significantly lower serum magnesium concentrations throughout pregnancy than did nondiabetics. They also had significantly lower parathyroid hormone levels after midpregnancy, because the progressive increase in parathyroid hormone concentration observed in control subjects did not occur in diabetics. There was no significant difference between pregnant diabetics and nondiabetics in serum concentrations of total calcium, ionized calcium, phosphorus, or albumin or in plasma levels of calcitonin.

Calcitonin↗
PubMed1980

Maternal and fetal parathyroid hormone responsiveness in pregnant primates.

Maternal and fetal parathyroidd hormone (PTH) responsiveness to hypocalcemia induced by EDTA infusion (50 mg/kg over 2 h) was studied in rhesus monkeys in late pregnancy. Although baseline serum total calcium (Ca) levels in the fetus exceeded those in the mother (4.83 +/- 0.13 vs. 4.28 +/- 0.15 meq/liter; P < 0.001), PTH values were not significantly different (5.62 +/- 0.37 vs. 6.18 +/- 0.33 muleq/ml; P > 0.05). EDTA infusion directly to five fetuses produced significant hypocalcemia (maximal decline averaging 19 +/- 2%) and PTH response (maximal increase averaging 46 +/- 5%). In contrast, in four control studies involving fetal saline infusion, there were no significant changes in fetal Ca or PTH levels. Four maternal control infusions produced no significant changes in either Ca or PTH levels. A comparison of maternal and fetal PTH responses indicated considerable similarity, although fetal PTH levels tended to return to baseline somewhat more gradually after cessation of the hypocalcemic stimulus than did maternal levels. These studies indicate that fetal PTH secretion, both baseline and in response to hypocalcemia, is quantitatively similar to that of the adult, and thus, the fetal parathyroid does not appear to be suppressed by the relative hypercalcemia of late fetal life.

Animals↗
PubMed1980

Fetal calcitropic hormones and neonatal calcium homeostasis.

Ionic calcium (Ca2+), total calcium, magnesium, phosphorus, albumin, immunoreactive parathyroid hormone (PTH), and immunoreactive calcitonin (CT) were measured in maternal and cord blood at term delivery of 96 women near term with predominantly normal pregnancies. Calcium, magnesium, phosphorus, and albumin were measured in the infants at 24 hours of age. Umbilical Ca2+ levels exceeded maternal values significantly (2.82 +/- 0.15 vs 2.23 +/- 0.09 mEq/liter, P < .001), as did calcium, magnesium, phosphorus, and albumin levels. The relative fetal hypercalcemia was associated with significantly higher CT levels in fetus than in mother (248 +/- 68 vs 209 +/- 54 pg/ml, P < .05) but PTH concentrations did not differ significantly between the two circulations. Within the fetal circulation, levels of each component did not differ except for PTH which was in higher concentration in venous than in arterial blood (5.50 +/- 1.81 vs 4.93 +/- 1.71 microliter-eq/ml, P < .05). Stepwise multiple regression analysis, utilizing neonatal Ca level as the dependent variable, identified one clinical feature (duration of pregnancy) and six laboratory data as significant independent variables, account in sum for 35% of the variation in neonatal calcium level. The significant laboratory variables, in order of entry into the model, were maternal PTH, umbilical venous PTH, maternal phosphorus, umbilical venous magnesium, neonatal albumin, and neonatal magnesium. These results indicate that the normal fetus responds to hypercalcemia in late intrauterine life by increasing CT secretion but not by suppressing PTH output. The umbilical PTH level is one of several factors at birth which correlates significantly with calcium concentration at 24 hours of age.

Calcitonin↗
PubMed1979

Effects of magnesium sulfate treatment on perinatal calcium metabolism. I. Maternal and fetal responses.

Serial maternal and cord blood determinations of the ions and hormones involved in calcium homeostasis were made in pre-eclamptic women treated with intravenous magnesium sulfate. A 4 gm loading dose followed by 1 to 2 gm/hr caused maternal serum magnesium concentrations to rise 150%, to levels of 3.3 to 4.5 mEq/L, and ionized calcium levels to fall 16%, to 1.89 mEq/L. The hypocalcemia etly altering calcitonin. Changes in total calcium paralleled those of ionized calcium; phosphorus levels were not affected by magnesium infusion. At the time of delivery the offspring of these women were hypermagnesemic and relatively hypocalcemic, although less so than their mothers. Fetal ionized calcium levels, although lower with magnesium treatment than in control subjects, were within the lower limits of the normal range, which perhaps explains why the fetus did not respond with increased PTH or decreased calcitonin output. These results indicate that the principal maternal response to magnesium-induced hypocalcemia involves increased parathyroid hormone secretion which tends to preserve maternal calcium homeostasis, while the fetus is partially protected from hypermagnesemia and hypocalcemia by the placenta.

Adult↗
PubMed1979

Calcium metabolism in normal pregnancy: a longitudinal study.

Total and ionic calcium, magnesium, phosphorus, albumin, and immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) were measured in serum or plasma from 30 women throughout pregnancy (beginning before 12 weeks' gestation) and the puerperium. Total calcium levels declined during gestation, paralleling a progressive fall in albumin concentration, whereas ionic calcium values declined only very slightly. Although iPTH levels in early pregnancy were lower than postpartum values (suggesting that iPTH may decline initially following conception), the major portion of gestation was characterized by progressively increasing concentrations which at term averaged 53% above early pregnancy levels and 33% above puerperal values. Thus, the principal adjustment during pregnancy is "physiologic hyperparathyroidism" which acts to preserve maternal homeostasis by maintaining the concentration of calcium ions in extracellular fluid in the presence of expanding fluid volume, increased renal function, and placental transfer. iCT levels were not affected consistently by pregnancy and exhibited highly variable patterns; half of the subjects demonstrated an increase during the first and second trimesters and then a decline in the third trimester and the remaining half was equally divided between those with no change and those with progressively falling levels.

Adult↗
PubMed1979

Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin.

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.

Animals↗
PubMed1978

Effect of somatostatin on parathyroid hormone and calcitonin secretion.

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.

Animals↗
PubMed1978

Comparative effect of calcium and of the adrenergic system on calcitonin secretion in man.

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.

Adult↗
PubMed1978

Calcium-regulating hormones during the menstrual cycle.

Calcium metabolism during the menstrual cycle was studied in seven women from whom fasting blood samples were drawn daily or every other day throughout ovulatory cycles. Total calcium (Ca), ionic calcium (Ca++), magnesium (Mg), phosphorus (P), and immunoreactive parathyroid hormone (PTH) and calcitonin (CT) were measured. LH levels were used to date each cycle and progesterone levels were used to confirm ovulation. Plasma estradiol was measured in two of the subjects. In six subjects with cycle lengths of 27-31 days, PTH levels rose progressively through the follicular phase to a peak at or slightly before the LH surge, then fell progressively through the luteal phase; peak PTH levels were 30-35% above early follicular and late luteal values. CT levels were also highest at midcycle, but the CT pattern was somewhat more variable than that of PTH. Ca++ tended to fall until 3-4 days before ovulation and then to increase, while Ca, Mg, and P exhibited no particular pattern. One subject experienced a prolonged (44 day) ovulatory cycle characterized by three distinct PTH peaks, each of which coincided with elevations in plasma estradiol level. These results represent the first report of menstrual cyclicity in calcium-regulating hormones. The timing suggest an estrogen effect and it is hypothesized that estrogen inhibits PTH-induced bone resorption, lowering serum Ca++, which in turn provokes a compensatory PTH output. With the decline of the preovulatory estrogen peak, Ca++ levels rise and PTH secretion falls. Alternatively, it is possible that the primary action may be an estrogen-induced rise in CT release, causing hypocalcemia and consequent PTH output. Cyclic changes in PRL release or vitamin D metabolism might also be involved.

Calcitonin↗
PubMed1978

Radioimmunoassay of calcitonin in the plasma of rhesus monkey and man.

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.

Animals↗
PubMed1977

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.

Adult↗
PubMed1977

Radioimmunoassay of parathyroid hormone (parathyrin) in monkey and man.

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.

Adult↗
PubMed1977

Secretory and ultrastructural responses of hyperfunctioning human parathyroid tissues to varying calcium concentration and vinblastine.

Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.

Adenoma↗