bluuebunny/crossref_metadata_2025 huggingface dataset:
Osmotic control of plasma vasopressin in the dog
Authors: Wade C. E. , Bie P. , Keil L. C. , Ramsay D. J.
Published: December 2017

Seven dogs prepared with carotid loops were used to evaluate the responsiveness of the cerebral osmoreceptors regulating plasma vasopressin concentration (pAVP). Intracarotid and intravenous infusions of hypo- and hypertonic solutions were used to alter cerebral plasma osmolality. Bilateral intracarotid infusion of hypertonic saline (0.90 mmol NaCl kg-1 . min-1 . artery-1) significantly elevated jugular vein plasma osmolality (pOsm) in the first minute (P less than 0.05). Systemic values, determined from saphenous vein samples, were increased after 6 min. After 4 min of infusion, systemic pAVP was significantly increased, attaining a constant level at 6 min. Subsequent experiments with infusions 6 min in duration demonstrated that hypertonic saline infused intracarotidly significantly increased pAVP in a dose-related fashion, whereas similar solutions administered intravenously did not alter pAVP. Hypotonic infusions (intravenous or intracarotid) did not change pAVP consistently. The lack of a depression in pAVP during hypotonic infusions is consistent with the argument that jugular pOsm must be elevated above a threshold to stimulate the release of vasopressin. Linear relationships were demonstrated for jugular pNa+ and pOsm to pAVP employing the threshold model. Cerebral osmoreceptors that regulate plasma vasopressin concentration respond linearly to increasing tonicity above a threshold stimulating the release of vasopressin.
N tau-methylhistidine release: contributions of rat skeletal muscle, GI tract, and skin
Authors: Wassner S. J. , Li J. B.
Published: December 2017

The relative contributions of skeletal muscle, gastrointestinal tract, and skin to urinary N tau-methylhistidine (MH) excretion were estimated during in vitro studies using the rat hemicorpus preparation. After 0.5 h of perfusion, MH release into the perfusate was linear for 3 h and averaged 29.8 nmol . h-1 . 100 g hemicorpus-1. In vivo, 24-h urinary MH excretion averaged 37.3 nmol . h-1 . 100 g body wt-1. The ratio of soft tissue to skin weight is equal (3.2:1) in the whole rat and in the hemicorpus. The gastrointestinal tract released 16.0 nmol . h-1 . 100 g body wt-1 or approximately 41% of the total urinary MH excretion. Preparations perfused with or without skin showed modest differences in the rate of MH release that were not statistically significant. Skeletal muscle contains 89.8% of total body MH content, whereas gastrointestinal tract and skin contain 3.8 and 6.4%, respectively. Gastrointestinal tract actomyosin turns over rapidly with a fractional catabolic rate of 24%/day versus 1.4%/day for skeletal muscle actomyosin.
Antifolliculogenic action of progesterone despite hypersecretion of FSH in monkeys
Authors: Goodman A. L. , Hodgen G. D.
Published: December 2017

To learn how progesterone (P) inhibits follicle growth during the luteal phase, we determined whether P will inhibit follicle growth when follicle-stimulating hormone (FSH) is secreted in large amounts, namely, after luteectomy (CLX) in monkeys with only one ovary. Second, a functional role for 17 alpha-hydroxyprogesterone (17OHP) was examined as a common mediator of the inhibition of folliculogenesis by the dominant follicle and corpus luteum. To accomplish the first goal, nine chronically hemiovarectomized monkeys were lutectomized chronically hemiovariectomized monkeys were luteectomized at midluteal phase. In five monkeys that received no steroid, the next preovulatory luteinizing hormone (LH) surge occurred 14.0 +/- 0.8 days (mean +/- SE) after CLX. In contrast, the next LH surge was delayed in four monkeys implanted for 10 days with Silastic capsules containing P and occurred 25.0 +/- 2.7 days after CLX, i.e., 14.8 +/- 2.7 days after the capsule removal. In both groups, FSH levels increased markedly after CLX to a comparable degree and duration; yet, only a single follicle ovulated in each monkey. To examine a potential inhibitory role for 17OHP, monkeys with two ovaries were luteectomized and received 1) no steroid, 2) 17OHP via Silastic capsules, or 3) P for 10 days after CLX. Progesterone replacement after CLX appeared to maintain 17OHP levels, which showed a transient decrease after CLX alone. As above, P delayed the next LH surge (25.4 +/- 1.3 vs. 15.0 +/- 0.6 days) despite comparable increases in serum FSH after CLX alone. Replacement at two levels of 17OHP did not delay the onset of menses (2-3 days post-CLX) or significantly delay the next LH surge 18.3 +/!- 1.9 or 20.8 +/- 3.4 vs. 15.0 +/- 0.6 days (P greater than 0.2) in monkeys CLX only. Whatever may be the mode of action of P, it appears that it is not mediated by peripheral conversion to 17OHP. These findings demonstrate that P at luteal phase levels can inhibit follicle growth culminating in ovulation even in the face of sustained, elevated levels of endogenous FSH. Because single ovulations occurred despite unambiguous and prolonged increments in serum FSH after CLX, the precise regulation of the ovulatory quota in this primate appears to be accomplished by means other than FSH alone.
Acute inhibition of PRL and TSH secretion after intraventricular injection of PRL in ovariectomized rats
Authors: Mangat H. K. , McCann S. M.
Published: December 2017

Prolactin (PRL) is under short-loop inhibitory control via the hypothalamus. However, earlier studies evaluated the effects on PRL secretion of PRL levels elevated for periods of days. In this study we evaluated the acute effects of intraventricular and systemic injection of PRL on the release of a variety of pituitary hormones. Ovariectomized (OVX) rats, bearing implanted third ventricular and jugular cannulas were used. Blood was withdrawn in unanesthetized, freely moving animals before and after intraventricular injection of 0.9% NaCl or 1 or 3 micrograms of bovine (b) or ovine (o) PRL. Prolactin was also administered intravenously in doses of 3 or 6 micrograms. No effect on plasma levels of any of the pituitary hormones occurred after intraventricular or systemic injection of saline. Intraventricular injection of both doses of bPRL or oPRL significantly lowered plasma PRL within 15-30 min. In animals with elevated initial PRL values because of stress or estradiol (E) priming, greater lowering of PRL occurred. Inconsistent reductions in plasma PRL occurred after intravenous injection of oPRL but not bPRL, which elevated PRL values via cross-reaction in the immunoassay. In contrast, only small and inconsistent declines in luteinizing hormone (LH) were seen after intraventricular injection of PRL in either OVX or OVX E-primed rats. Plasma follicle-stimulating hormone (FSH) and growth hormone (GH) were not affected by PRL in any of the experiments; however, a significant lowering of thyrotropin (TSH) occurred in OVX or OVX E-primed rats within 30 min after intravenous injection of 3 micrograms of oPRL, but no change occurred after intravenous PRL. The data indicate that PRL can acutely inhibit PRL and TSH release via a hypothalamic action, whereas release of LH is only slightly inhibited and that of FSH and GH is unaltered.
Glucose production measured by tracer and balance data in conscious miniature pig
Authors: Muller M. J. , Paschen U. , Seitz H. J.
Published: December 2017

The rate of glucose production was estimated in the conscious, unrestrained miniature pig during metabolic adaptation to starvation (up to 120 h) by the simultaneous use of three different techniques: 1) the isotopedilution technique, 2) the arteriohepatovenous catheter technique, and 3) the urinary nitrogen balance. During the experimental period 1) whole-body glucose turnover decreased, whereas the amount of glucose recycling increased; 2) splanchnic glucose output decreased, whereas the rate of splanchnic precursor extraction increased up to 48 h, followed by a decrease; 3) gut glucose consumption amounted to about 30% of splanchnic glucose output; and 4) urinary nitrogen excretion declined continuously. The comparison of the different methods revealed that during starvation 1) tracer-determined glucose production rate was within the range (+/- 10%) of the splanchnic glucose output; 2) mean hepatic glucose output overestimated the tracer data by about 30-40%; 3) splanchnic glucose output underestimated hepatic glucose production by the amount of gut glucose consumption; 4) tracer-determined glucose recycling corrected for isotope dilution and amino acid contribution was within the range of splanchnic gluconeogenic precursor extractions. Considering the limitations (e.g., gut glucose consumption, gut lactate and alanine release, blood flow measurement) and methodological problems of the different approaches applied, it is evident that each method reflects different events. It is suggested that the versatile tracer technique combined with nitrogen balance should be preferred for measurement of endogenous glucose production.
1- but not 24-hydroxylation of vitamin D is required for growth and reproduction in rats
Authors: Jarnagin K. , Brommage R. , DeLuca H. F. , Yamada S. , Takayama H.
Published: December 2017

This study examines whether 1,25-dihydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, an analogue of 25-hydroxyvitamin D3 blocked from undergoing 24-hydroxylation, can maintain normal growth and reproduction in the female rat. Vitamin D-deficient weanling rats were maintained from weaning through mating, pregnancy, and lactation with either 1,25-dihydroxyvitamin D3 (given by continuous subcutaneous infusion), 24,24-difluoro-25-hydroxyvitamin D3, 25-hydroxyvitamin D3, or vehicle. Body weight, plasma calcium levels, estrous cycling time, ability to give birth to live pups, litter weight, number of pups per litter, dam plasma calcium level during lactation, and pup growth to 9 wk of age were recorded. No striking differences were observed between the 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group. However, significant differences in most parameters were observed between the vitamin D-deficient and metabolite- or analogue-dosed rats. The results demonstrate that 1,25-dihydroxyvitamin D3 and/or one of its metabolites is sufficient to maintain normal growth, development, and reproductive functions in the female rat. Because 24,24-difluoro-25-hydroxyvitamin D3 cannot be hydroxylated at C-24, the 24-hydroxylation of 25-hydroxyvitamin D3 is not essential for normal growth, development, and reproduction in the female rat.
Responsiveness of vitamin D-deficient fetal rat limb bones to parathyroid hormone in culture
Authors: Stern P. H. , Halloran B. P. , DeLuca H. F. , Hefley T. J.
Published: December 2017

Radii and ulnae from 19-day fetal rats from normal or vitamin D-deficient mothers were treated with 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, or parathyroid hormone in vitro. Both sets of bones resorbed in response to all three agents. Statistical analysis indicated a purely additive model for the effects of vitamin D status and the bone-resorbing agents, with no evidence for interaction. The results suggest that the impaired calcemic response to parathyroid hormone seen in vitamin D-deficient animals in vivo is not the result of a specific unresponsiveness of vitamin D-deficient bone to parathyroid hormone.
Cardiovascular effects and clearance of arginine vasopressin in the fetal lamb
Authors: Wiriyathian S. , Porter J. C. , Naden R. P. , Rosenfeld C. R.
Published: December 2017

Increased fetal secretion of arginine vasopressin (AVP) occurs in association with complicated pregnancies, asphyxia, and meconium-stained amniotic fluid (AF); yet, the role of AVP in fetal homeostasis remains unclear. Using chronically instrumented, near-term lamb fetuses (n = 8), we have ascertained the cardiovascular responses to doses of AVP ranging from 1.94 to 8.73 mU/min, the clearance of AVP from plasma, and the occurrence of meconium release into AF during AVP infusions. AVP administration resulted in a dose-related rise in arterial pressure; although heart rate fell, the decline was not dose-related and occurred before the pressor response. Clearance of plasma AVP was 60 +/- 8.7 ml X kg-1 X min-1, and the half-time in plasma was 2.8 min. AVP was not cleared across the fetal placenta nor by fetal-maternal transport. However, the AF concentration of AVP rose fourfold after the infusion of AVP was stopped. Meconium release into AF occurred in fetuses infused with AVP at rates greater than or equal to 7.76 mU/min. AVP has hemodynamic effects that mimic fetal responses to intrauterine "stress" and may be causally associated with the fetal release of meconium into AF. Furthermore, plasma AVP is cleared in part by the fetal kidney.
Sympathetic nervous system and adrenal medullary responses to ischemic injury in mice
Authors: Young J. B. , Fish S. , Landsberg L.
Published: December 2017

Acute, severe injury is frequently attended by hypotension, hypothermia, and decreased metabolic rate despite elevated urine and plasma catecholamine levels. Because the combination of sympathetic nervous system (SNS) suppression and adrenal medullary stimulation documented in several other situations could account for these observations, SNS and adrenal medullary function were examined independently in mice in the hindlimb ischemia model of acute injury. SNS activity was assessed by the measurement of [3H]norepinephrine (NE) turnover in heart and adrenal medullary secretion by depletion of adrenal catecholamine content. In nine separate experiments during the first 10 h after termination of a 2.5-h period of hindlimb ischemia, cardiac NE turnover was reduced an average of 23% (P less than 0.05) in injured mice. At the same time, adrenal catecholamine content fell 37% (P less than 0.05) in injured animals but not in controls. In contrast to the acute reaction, SNS activity in mice surviving 3 days was 59% greater than in controls. Thus, the reduction in NE turnover and depletion of adrenal catecholamine content suggest that SNS suppression and adrenal medullary stimulation constitute the acute sympathoadrenal response in this model of severe injury. Because survival within the first 24 h after injury was decreased in adrenalectomized mice despite glucocorticoid treatment, adrenal medullary catecholamines may contribute to survival in severely injured animals. Furthermore, because the SNS plays an important role in the regulation of blood pressure and heat production, the diminution in SNS activity in the hours after injury may contribute to posttraumatic hypotension and hypometabolism.
Distribution of acute-phase alpha 2-macroglobulin in rat fetomaternal compartments
Authors: Panrucker D. E. , Lai P. C. , Lorscheider F. L.
Published: December 2017

Rat acute-phase alpha 2-macroglobulin (AP alpha 2M) concentration was measured by radioimmunoassay in maternal serum, fetal plasma, maternal liver, fetal liver, and amniotic fluid as a function of gestational and neonatal age. The concentration profiles of AP alpha 2M in maternal serum and fetal plasma displayed two peaks, one in early gestation and another during late gestation. Synthesis of AP alpha 2M was confirmed by the immunoprecipitation of [35S]methionine incorporated into cultures of selected tissues. The following observations were made. 1) Maternal serum concentrations of AP alpha 2M were higher than those observed in fetal plasma in early gestation. This was attributable to a high level of maternal AP alpha 2M synthesis in metrial gland which was absent in liver and moderate in yolk sac. 2) In late gestation fetal plasma concentrations of AP alpha 2M greatly exceeded those observed in maternal serum. This could be explained by the pronounced synthesis of AP alpha 2M in fetal liver that was not apparent in maternal liver or yolk sac. 3) During labor, a transient increase in AP alpha 2M concentration was observed in maternal serum and fetal plasma. 4) During lactation a moderately elevated maternal serum concentration of AP alpha 2M was maintained. 5) Amniotic fluid concentration of AP alpha 2M was very low throughout gestation, which indicated that the fetal glomerulus was relatively impermeable to this large protein. It is concluded that in early gestation a principal maternal source of AP alpha 2M appears to be the metrial gland, whereas in late gestation fetal liver is a major source of AP alpha 2M appearing in fetal plasma from where some of this macroglobulin is speculated to be transported to the maternal circulation.
Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3
Authors: Reddy G. S. , Jones G. , Kooh S. W. , Fraser D. , DeLuca H. F.
Published: December 2017

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.
Absence of hepatic extraction of pancreatic polypeptide in conscious dogs
Authors: Ishida T. , Chou M. C. , Chou J. , Lewis R. M. , Hartley C. J. , Entman M. , Kimmel J. R. , Field J. B.
Published: December 2017

In 15 conscious dogs basal portal vein pancreatic polypeptide (PP) (306 +/- 8 pg/ml) exceeded both hepatic vein PP (255 +/- 8 pg/ml) and arterial PP (244 +/- 9 pg/ml) and increased rapidly 10 min after oral glucose administration. In contrast to oral glucose, intraportal glucose infusion decreased PP levels from 45 min until the end of the infusion. Meat ingestion rapidly and promptly increased PP. During the basal state, hepatic extraction of total immunoreactive PP was 10 +/- 4%, not significantly different from zero, of the 150 +/- 14 ng/min presented to the liver. Fractional hepatic extraction of PP did not change after oral glucose, meat ingestion, or intraportal glucose infusion. Chromatographic analysis showed at least four different components of immunoreactive PP. The first peak eluted with the void volume, the second peak between the void volume and authentic PP, and the third peak coincided with authentic PP. When present, the fourth peak eluted after authentic PP. More than half of the immunoreactive PP in the basal state eluted with authentic PP, whereas about one-third was found in the second peak. The marked alterations in PP after meat, oral glucose, or intraportal glucose and atropine reflected primarily changes in the third peak. The fractional hepatic extraction of all the components was very similar.
Response of liver glycogen synthase and phosphorylase to in vivo glucose and glucose analogues
Authors: Nuttall F. Q. , Theen J. W. , Niewoehner C. , Gilboe D. P.
Published: December 2017

Glucose causes a rapid increase in the proportion (%) of glycogen synthase in the active (I) form and a rapid decrease in the proportion of phosphorylase in the active (a) form in both fed and fasted rats. The changes in synthase I and phosphorylase a are more rapid in fasted animals. With graded doses of glucose, the maximal decrease in phosphorylase a occurred at a dose that was considerably smaller than that required to maximally stimulate an increase in % synthase I. Thus, in the intact animal a dissociation between the effects of glucose on the synthase and phosphorylase systems was observed. Sorbitol, mannose, galactose, and arabinose all stimulated an increase in synthase I but did not significantly affect the proportion of phosphorylase in the a form. The % synthase I was not significantly affected by a number of other glucose homologues, pentoses, or three-carbon gluconeogenic substrates. The ketoses fructose and mannoheptulose both caused a striking increase in % phosphorylase a and a decrease in % synthase I, i.e., results opposite to those of glucose. The mechanism by which fructose induces these changes is not known, but the mannoheptulose effects may be accounted for by a rise in liver cAMP concentration.
Altered sensitivity of chronic diabetic rat heart to calcium
Authors: Bielefeld D. R. , Pace C. S. , Boshell B. R.
Published: December 2017

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.
Mechanism of arginine-stimulated Ca2+ influx into pancreatic B cell
Authors: Herchuelz A. , Lebrun P. , Boschero A. C. , Malaisse W. J.
Published: December 2017

The mechanism by which arginine stimulates Ca2+ inflow into the pancreatic B cell was investigated. Arginine (10 mM) increased 86Rb outflow from perifused rat pancreatic islets, suggesting that arginine-stimulated Ca2+ influx into the B cell does not result from a decrease in K+ conductance. Arginine stimulated Ca2+ uptake in isolated islets over short incubation periods and increased 45Ca outflow from perifused islets in a Ca2+-dependent manner. The calcium channel blocker verapamil inhibited both arginine-stimulated 45Ca uptake and 45Ca outflow. However, the sensitivity toward verapamil of arginine-stimulated islets was lower than that of islets stimulated by 20 mM K+, which gates voltage-sensitive Ca2+ channels. It was similar to that of islets stimulated by 8.3 mM glucose, which is thought to mainly gate voltage-insensitive Ca2+ channels. It is suggested that arginine stimulates Ca2+ inflow into the B cell by gating voltage-insensitive Ca2+ channels. The arginine-induced stimulation of Ca2+ inflow could participate in the depolarizing action of the amino acid on the B cell membrane.
Dietary carbohydrate induces lipogenesis and very-low-density lipoprotein synthesis
Authors: Boogaerts J. R. , Malone-McNeal M. , Archambault-Schexnayder J. , Davis R. A.
Published: December 2017

Hepatocytes obtained from sucrose-fed rats secreted triacylglycerol at a rate that was about twice that of cells from control rats. The increased rate of triacylglycerol secretion by cells from sucrose-fed rats was accompanied by a twofold increase in its rate of synthesis as determined by 3H2O incorporation. In addition, cells from sucrose-fed rats had a two- to threefold increase in apolipoprotein synthesis. Differences between the two groups became even more marked when cells were challenged in vitro with glucose. Double-reciprocal analysis showed that compared with controls, cells from sucrose-fed rats had a fourfold increase in the Vmax that described the glucose stimulation of [3H]triacylglycerol secretion. In contrast to in vivo carbohydrate (sucrose) induction of apolipoprotein synthesis, glucose added in vitro did not affect apolipoprotein synthesis. These data suggest that in vivo induction by dietary carbohydrate requires factors in addition to increased hexose that are not contained within the isolated hepatocyte system. The coinduction by dietary carbohydrate of both lipogenesis and apolipoprotein synthesis is likely to play a role in the increased capacity of cells from sucrose-fed rats to both assemble and secrete triacylglycerol-rich lipoproteins.
Metabolic effects of oral glucose in the liver of fasted rats
Authors: Niewoehner C. B. , Gilboe D. P. , Nuttall F. Q.
Published: December 2017

Twenty-four-hour-fasted rats were given glucose (4 g/kg) by gavage. Glucose absorption and portal and peripheral plasma glucose, lactate, and insulin concentrations, as well as liver glucose, UDPglucose, glucose-6-P, lactate, ATP, and inorganic phosphate (Pi), and % glycogen synthase I and % phosphorylase a were measured at 10, 20, 30, 40, 60, and 120 min after the glucose was given. Liver and muscle glycogen also were measured. Ninety-one percent of the glucose load had disappeared from the gut in 2 h. Despite increased plasma glucose and insulin levels the liver continued to produce glucose. Lactate produced in the periphery was the major substrate for gluconeogenesis, and lactate utilization could account for the hepatic glycogen synthesized. Glucose ingestion did not affect lactate production by the splanchnic bed. In the liver glucose-6-P was transiently increased; UDP glucose decreased after glucose administration. ATP and Pi were unchanged. Glycogen synthase was activated by 20 min without a significant change in phosphorylase a. Hepatic glycogen increased linearly after 20 min. Total glucose storage as glycogen was similar in liver (20%) and muscle (19%). We could account for 41% of the glucose absorbed as glycogen, unmetabolized glucose, or glucose metabolites. Most of the remainder probably was oxidized.
Metabolic alterations after dehydroepiandrosterone treatment in Zucker rats
Authors: Shepherd A. , Cleary M. P.
Published: December 2017

Dehydroepiandrosterone (DHEA) is a known noncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PD). In the present investigation, the effects of chronic DHEA treatment on G6PD and several other enzymes involved in lipid metabolism were examined in lean and obese Zucker rats. Significant decreases in body weight were found in DHEA-treated rats in comparison with nontreated rats. In lean rats, DHEA treatment did not decrease either liver or adipose tissue G6PD and fatty acid synthetase activity, but malic enzyme activity was increased. In obese rats, decreased liver and adipose tissue G6PD and fatty acid synthetase activities were found. Malic enzyme activity in liver of obese DHEA rats was increased but not in adipose tissue. Adipose tissue lipoprotein lipase activity was decreased in both lean and obese DHEA rats. Serum insulin in obese DHEA rats was also decreased compared with control obese rats. These results indicate that the inhibition of G6PD may not be the mechanism of action of the antiobesity effect of DHEA. However, the metabolic effects of DHEA seen in obese rats may contribute to its antiobesity action.
Influence of converting-enzyme inhibition on rat des-angiotensin I-angiotensinogen
Authors: Clauser E. , Bouhnik J. , Gonzalez M. F. , Corvol P. , Menard J.
Published: December 2017

The effects of high plasma renin levels on plasma levels of both total immunoreactive angiotensinogen (direct radioimmunoassay) and intact angiotensinogen measured by angiotensin I released by renin (indirect assay) were studied in sodium-depleted rats both with and without captopril treatment and in adrenalectomized rats. The direct assay measures both intact angiotensinogen and des-angiotensin I-angiotensinogen, its residue cleaved by renin. The indirect assay measures only intact angiotensinogen. Neither sodium depletion, captopril treatment, nor adrenalectomy modified the circulating levels of total angiotensinogen. However these treatments produced a decrease in intact angiotensinogen that was in proportion to the elevation of renin levels. The difference between the two assays for angiotensin represents the level of des-angiotensin I-angiotensinogen and correlated satisfactorily with the plasma levels of renin. Identical correlations were observed in adrenalectomized rats and captopril-treated rats. We conclude that des-angiotensin I-angiotensinogen levels are an index of activation of the renin-angiotensin system dependent on the circulating level of renin.
Fetal glucose uptake and utilization as functions of maternal glucose concentration
Authors: Hay W. W. , Sparks J. W. , Wilkening R. B. , Battaglia F. C. , Meschia G.
Published: December 2017

Seventeen studies were performed in 12 pregnant sheep to examine the relationship among simultaneously measured glucose uptake via the umbilical circulation, fetal glucose utilization (mg X min-1 X kg-1), and maternal arterial glucose (Gm, mg/dl). Fetal glucose utilization was measured by means of tracer glucose infused into the fetus or both mother and fetus. By fasting the ewe, Gm was varied in the 62-22 range. A decrease in Gm was accompanied by a significant (P less than 0.001) decrease in umbilical uptake (uptake = 0.09 Gm - 0.96, r = 0.82) and in fetal utilization, measured either by [U-14C]glucose (utilization = 0.062 Gm + 0.91, r = 0.90) or [6-3H]glucose (utilization = 0.065 Gm + 0.51, r = 0.91). At uptake greater than 3 mg X min-1 X kg-1, utilization and uptake were not significantly different. At lower uptakes, utilization did not decline as much as uptake. The results demonstrate that maternal fasting decreases both the umbilical uptake and the fetal utilization of glucose and suggest that fetal glucogenesis increases when the availability of exogenous glucose is markedly reduced.
Effect of physical training on utilization of a glucose load given orally during exercise
Authors: Krzentowski G. , Pirnay F. , Luyckx A. S. , Lacroix M. , Mosora F. , Lefebvre P. J.
Published: December 2017

The effect of a 6-wk training period on the oxidation of a 100-g glucose load given orally during exercise was investigated in six healthy male volunteers. The subjects were submitted before and 24 h after the training program to a 105-min exercise bout (performed at about 40% of the pretraining VO2max) followed by a 90-min resting period. Naturally labeled [13C]glucose was given 15 min after the beginning of exercise. Exogenous glucose oxidation was derived from 13CO2 measurements in expired air, and total glucose and lipid oxidation were evaluated by indirect calorimetry. Training (60-min bicycling 5 days a week at 30-40% VO2max) resulted in a 29% increase in VO2max. During the 15 min of exercise that preceded glucose ingestion, the rate of total carbohydrate oxidation was slightly decreased after training, whereas the rate of lipid oxidation was slightly increased. Training did not affect the response of blood glucose, plasma insulin, or plasma free fatty acids to the glucose ingested during exercise; in contrast, the circulating levels of epinephrine, glycerol, and lactate were significantly reduced after training. Substrate utilization measurements revealed similar oxidation rates of carbohydrates (106.9 +/- 2.7 before vs. 100.2 +/- 4.7 g/3 h after training) and of lipids. However, detailed analysis revealed a significant 17% increase in exogenous glucose oxidation, thus indicating a significant sparing of endogenous carbohydrates. In conclusion, physical training induces a modest but significant increase in the oxidation of an oral load of glucose given during subsequent exercise of moderate intensity, a phenomenon reinforcing the sparing of endogenous carbohydrate stores.
Effects of chronic estrogen treatment on water exchange in rats
Authors: Carlberg K. A. , Fregly M. J. , Fahey M.
Published: December 2017

Intact female rats implanted subcutaneously with Silastic tubes containing estradiol benzoate (EB) (28.7 micrograms X kg-1 X day-1) for 28 wk had a significantly greater daily intake of water, a higher water-to-food intake ratio, and a greater urine output than untreated control rats. Ovariectomized (OVX) rats also implanted for 14 wk with EB tubes (15 and 36 micrograms X kg-1 X day-1) showed identical results. Dipsogenic responses of the EB-treated rats to isoproterenol (25 micrograms/kg sc), angiotensin II (200 micrograms/kg ip), and hypertonic saline (1 M, 1% of body wt ip) were significantly attenuated. Both intact and OVX rats were subjected to a 24-h dehydration to assess renal concentrating ability. EB-treated rats lost significantly more weight and excreted significantly more urine of lower osmolality than controls. Administration of vasopressin to volume-loaded, EB-treated rats revealed no abnormalities in the ability to concentrate urine to the level of controls. Thus, in spite of a reduced responsiveness to several dipsogenic stimuli, EB-treated rats have an increased daily water turnover apparently related to an inability to concentrate their urine. This in turn may be related to abnormalities in either synthesis or release of antidiuretic hormone or both.
Identification and regulation of adrenergic receptors in target cells
Authors: Insel P. A.
Published: December 2017

The application of radioligand binding techniques has recently led to increased understanding of adrenergic receptors, the recognition sites for catecholamines on target cells. Radioligand binding is a simple technique to conduct, although data obtained from binding studies are not always as easy to interpret as they are to generate. Nevertheless, the goal of these studies is to help define the molecular physiology of catecholamine action. In this article, I address five principal questions that largely dominate current research on adrenergic receptors. 1) How many types and subtypes of adrenergic receptors exist? 2) What is the structure of adrenergic receptors? 3) How is occupancy of adrenergic receptors translated to changes in target cell response? 4) How do target cells regulate their complement of adrenergic receptors? 5) Do alterations in adrenergic receptors mediate altered pathophysiology in disease? Although only preliminary answers are available, the use of radioligand binding methodology, together with other biochemical, cell biological, immunological, and molecular biological approaches should provide the tools to obtain definitive answers to those questions within the near future.
Small doses of human chorionic gonadotropin prevent estradiol-induced luteolysis
Authors: Westfahl P. K. , Horton L. E. , Stadelman H. L. , Resko J. A.
Published: December 2017

The manner in which exogenous 17 beta-estradiol (E2) induces premature luteolysis in primates is unclear. In an effort to determine whether exogenous luteotropic hormone inhibits E2-induced luteolysis, E2 capsules were implanted subcutaneously in 11 cynomolgus macaques during the early luteal phase; six animals received injections of human chorionic gonadotropin (hCG; 7.5, 10, or 15 IU/day) for 10 days, and the remaining monkeys received saline. Blood was collected once daily for measurement of E2, progesterone, and bioactive luteinizing hormone (LH). Peak progesterone concentrations were between 0.7 and 5.0 ng/ml and declined prematurely in monkeys given E2 plus saline; the luteal phase was 11.5 +/- 0.6 days (mean +/- SE). With E2 plus hCG treatment, serum progesterone continued to increase after E2 capsule placement and reached peak levels of 4.0-13.0 ng/ml; the luteal phase was 15.3 +/- 0.5 days. Therefore, E2-induced luteolysis was overcome by concurrent administration of hCG. These results suggest that exogenous tropic hormone circumvents the inhibitory influence of E2 on luteal function, but the details of the interaction remain unknown.
Catecholamine responses to hypocaloric diets and fasting in obese human subjects
Authors: Leiter L. A. , Grose M. , Yale J. F. , Marliss E. B.
Published: December 2017

Catecholamines have multiple metabolic and fluid-electrolyte as well as cardiovascular effects, and their levels in plasma respond to alterations in nutrient and sodium intakes. Plasma norepinephrine, epinephrine, and dopamine were measured in 12 obese nondiabetic subjects before and after 400 kcal/day diets of either protein or glucose, followed by total fasting, and then by hypocaloric refeeding, each for 14-day periods. Measurements were made in the supine and upright posture and during and after 6-10 min of exhaustive exercise at 80% maximal VO2. Sodium intake varied with the nutrients ingested, being markedly decreased with the 400 kcal/day diets and fasting. Norepinephrine levels were higher in fasting than base line while subjects were lying or standing and after recovery from exercise. Those of epinephrine were elevated on standing. No differences were found after the 400 kcal/day diets, with protein and glucose yielding equivalent results. In contrast, refeeding was associated with lower norepinephrine levels than all other diets while subjects were lying or standing and after recovery from exercise. Peak levels of norepinephrine and epinephrine with exercise were indistinguishable among diets. Fasting was associated with lower systolic and diastolic blood pressures and lower responses to standing and exercise than base line, whereas upright heart rate was greater and that during exercise less than base line. Significant though less extensive changes occurred with the other diets. Thus both electrolyte status and nutrient intakes interact to determine net catecholamine responses, and the former seem to override the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
Fasting and diabetes alter adipose tissue glycogen synthase
Authors: Kaslow H. R. , Eichner R. D.
Published: December 2017

In a previous report (J. Biol. Chem. 254: 4678-4683, 1979), we showed that fasting blunted the ability of insulin to promote glucose incorporation into glycogen in vitro. In addition, we showed that glycogen synthase activity was altered in two ways: the concentration of glucose 6-P causing half-maximal activation increased, and positive cooperativity appeared in the glucose 6-P activation of the enzyme. We now show that streptozotocin-diabetes causes the same changes in glucose incorporation and glycogen synthase activity. We show that these changes in glycogen synthase activity persist during enzyme purification; thus it is likely the changes are a result of a structural alteration of the enzyme. Because glycogenolysis of a glycogen particle from rabbit skeletal muscle also caused the appearance of positive cooperativity, we propose that both phosphorylation and glycogenolysis are involved in the appearance of positive cooperativity.
Mechanisms of synergism between glucose and cAMP on stimulation of insulin release
Authors: Phang W. , Domboski L. , Krausz Y. , Sharp G. W.
Published: December 2017

The mechanism of synergism between glucose and adenosine 3',5'-cyclic monophosphate (cAMP) on insulin release has been studied. Synergism may result from 1) inhibition of Na+-Ca2+ exchange by glucose and 2) a cAMP-induced sensitization of the release machinery to Ca2+. To distinguish between these two possibilities, isolated rat pancreatic islets were perifused with agents that raise intracellular levels of cAMP [3-isobutyl-1-methylxanthine (IBMX) and forskolin] and others that increase intracellular concentrations of Ca2+ either by blocking Na2+-Ca2+ exchange (ouabain and choline-Ringer solution) or by causing increased Ca2+ influx (KCl, carbachol, and 10 mM Ca2+). The results indicate that both the combination of cAMP and increased Ca2+ influx or blocked Na2-Ca2+ exchange and increased Ca2+ influx potentiated insulin release. When the relative potentiating abilities of cAMP and blocked Na2+-Ca2+ exchange were compared by determining the individual effects of IBMX and 1 mM ouabain (a concentration that causes similar inhibition of 45C2+ efflux as 16.7 mM glucose) in the presence of carbachol, cAMP was only 1.4 times more potent as a potentiating agent than blocked Na+-Ca2+ exchange. The greatest potentiation of insulin release was observed when Na+-Ca2+ exchange was blocked in the presence of increased levels of intracellular cAMP.
Specific binding of serotonin in rat lung
Authors: Das D. K. , Steinberg H.
Published: December 2017

Mammalian lungs have been shown to store and to inactivate serotonin (5-HT) by an active process involving uptake and metabolism. 5-HT has direct action on lung including constrictor effects of pulmonary vascular and tracheobronchial smooth muscle, suggesting the presence of 5-HT receptors in lung. We have identified specific 5-HT binding of high affinity to the different lung portions and have shown that there was a different capacity for this binding. Two different 5-HT-binding capacities are present in a purified mitochondrial fraction. Saturation analysis of 5-[3H]HT binding to outer mitochondrial membranes demonstrates a single, temperature-sensitive, high-affinity and high-capacity binding (Kd = 8.3 +/- 1.2 nM, maximum binding capacity = 0.819 +/- 0.046 pmol/mg protein). The dissociation constant of inner mitochondrial membrane demonstrates a low-capacity site (Kd = 25.2 +/- 2.2 nM, maximum binding capacity = 0.453 +/- 0.037 pmol/mg protein). The purified microsomal fraction of lung exhibits a high-capacity binding site for 5-[3H]HT (Kd = 14.8 +/- 1.6 nM, maximum binding capacity = 0.760 +/- 0.03 pmol/mg protein). In addition to the lung being the major site for its inactivation, the presence of several specific 5-HT receptors may be related to some of the known 5-HT actions in lung and may suggest other unknown actions of this amine.
PGE2 binding, synthesis, and distribution in hen oviduct
Authors: Asboth G. , Todd H. , Toth M. , Hertelendy F.
Published: December 2017

Prostaglandin E2 (PGE2) bound specifically to particulate fractions prepared from the vagina and uterus (shell gland) portions of the hen oviduct in a time and temperature dependent fashion. Scatchard analysis indicated a single class of high-affinity binding sites in the vagina (Kd congruent to 1 nM), whereas the myometrium exhibited two kinds of binding site populations (Kd1 congruent to 1 nM, Kd2 congruent to 20 nM). It is suggested that these binding sites represent specific PGE2 receptors mediating the effects of PGE2 in oviductal smooth muscle. Vaginal particulate fractions produced approximately four times more prostanoids from [3H]-arachidonate than did uterine preparations. In the presence of epinephrine both tissues synthesized mainly thromboxane (TxB2), PGE2, and significantly less prostaglandin F2 alpha (PGF2 alpha). Addition of glutathione (GSH) or cytosol prepared from the oviduct markedly increased the yield of PGE2 at the expense of TxB2. Of the five morphologically discrete regions of the oviduct the vagina, infundibulum, and uterus contained the highest amounts of PGE and PGF, whereas the magnum and isthmus portions contain the least. TxB2 and 6-keto PGF1 alpha could not be detected in significant quantities in either region. These studies support the notion that PGE2 play a key role in the physiology of oviposition.
Calcium, a "third messenger" of cAMP-stimulated adrenal steroid secretion
Authors: Schiebinger R. J. , Braley L. M. , Menachery A. , Williams G. H.
Published: December 2017

This study examines the role of extracellular calcium and calcium mobilization from intracellular stores in mediating cAMP-stimulated steroid secretion by rat adrenal glomerulosa cells (GC) and fasciculata cells (FC). When GC were incubated acutely in a calcium-deficient buffer, cAMP failed to significantly increase aldosterone secretion above base line. Aldosterone secretion, however, rose from 17 +/- 2 to 32 +/- 4 ng/10(6) cells (P less than 0.01) as calcium in the medium was increased from 0 to 3.5 mM. In contrast, cAMP-stimulated corticosterone production by FC was not influenced by changes in the external calcium concentration. Lanthanum (10(-4) M), an inhibitor of calcium influx, reduced cAMP-stimulated aldosterone secretion from 69 +/- 10 to 42 +/- 5 ng/10(6) cells (P less than 0.01) but failed to alter cAMP-stimulated fasciculata steroidogenesis. Depletion of intracellular calcium stores, achieved by incubating with EGTA, markedly blunted cAMP-stimulated corticosterone secretion in GC from 666 +/- 126 to 32 +/- 6 ng/10(6) cells (P less than 0.01), and cAMP-stimulated corticosterone secretion in FC from 2,223 +/- 407 to 414 +/- 58 ng/10(6) cells (P less than 0.01). TMB-8, a putative inhibitor of intracellular calcium mobilization, markedly inhibited (P less than 0.01) cAMP-stimulated aldosterone secretion by GC from 469 +/- 31 to 48 +/- 8 ng/10(6) cells and corticosterone secretion by FC from 9,867 +/- 1,821 to 2,832 +/- 586 ng/10(6) cells. These observations suggest that cAMP activation of adrenal steroidogenesis requires the release of calcium from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung growth in response to unilateral pneumonectomy in rapidly growing rats
Authors: Watkins C. A. , Burkhart L. R. , Rannels D. E.
Published: December 2017

The rapidity with which lung growth is initiated and completed after pneumonectomy was examined in young rats (4 wk of age; 82 g). After left pneumonectomy, the remaining lobes of the right lung grew to equal the weight of both lungs of control animals by day 7 and within 14 days increased from 366 to 968 mg. The tissue concentrations of RNA, DNA phosphate, collagen, and noncollagen proteins did not increase during the growth response. In contrast, total amounts of these constituents increased significantly in the remaining lung of pneumonectomized animals during the 1st postoperative wk and approached levels found in both lungs of sham-operated and unoperated controls by the end of the 2nd wk after pneumonectomy. Although cell size increased in control lungs during the experimental period, there was little evidence of additional cellular hypertrophy associated with compensatory lung growth. The character of the response to pneumonectomy in these rats was similar to that observed previously in older animals (320 g). Thus in spite of the higher basal rate of lung growth in the younger rats, the pattern and rapidity of compensation after pneumonectomy was similar in both age groups.
Analysis of tricarboxylic acid cycle using [14C]citrate specific activity ratios
Authors: Kelleher J. K.
Published: December 2017

The information content of citrate carbon specific radioactivity ratios in steady-state 14C isotopic studies has been analyzed. Sixteen steady-state equations resulted containing five unknowns, 14 equations in terms of citrate carbon specific radioactivity ratios, and two modified forms of the “CO2 ratio” equation. Although each of the 16 equations is not independent, there is more than one independent equation for each variable. These additional equations may be used to test the assumptions on which the model is based. Each of the five unknowns is defined as the probability of flux around a complete cycle, either the tricarboxylic acid (TCA) cycle or a futile cycle such as pyruvate--oxaloacetate--pyruvate. To solve these equations for the five unknowns, an investigator need only measure the specific radioactivity of various citrate carbons and the 14CO2 production rate. The study did not yield a direct expression for net flux between pyruvate and 4-carbon TCA cycle intermediates. However, these equations do place certain constraints on the net flux through this important pathway.