bluuebunny/crossref_metadata_2025 huggingface dataset:
Satiety and inhibition of vasopressin secretion after drinking in dehydrated dogs
Authors: Thrasher T. N. , Nistal-Herrera J. F. , Keil L. C. , Ramsay D. J.
Published: December 2017

The roles of oropharyngeal and gastric factors in satiation and arginine vasopressin (AVP) secretion were examined in water-deprived dogs. Dogs were prepared with chronic gastric fistulas and received six treatments after 24 h of water deprivation: rehydration with H2O or extracellular fluid (ECF) with the fistula closed; rehydration with H2O or ECF with the fistula open; gastric administration of H2O or ECF via the fistula. Drinking occurred immediately after presentation and was always completed by 6 min. At the end of the 60-min period of observation, water was offered in order to assess the degree of satiety. No differences were observed between the volumes of H2O or ECF consumed. However, only absorption of the water drunk produced complete satiety assessed 60 min later. Drinking H2O caused a fall in plasma AVP 6 min before a detectable decline in osmolality and reached water-replete levels by 15 min after drinking. Drinking H2O or ECF plus removal via the fistula and drinking ECF also brought about a rapid decline in plasma AVP without any change in plasma osmolality. Gastric administration of H2O caused a fall in plasma AVP that coincided with the fall in osmolality, and gastric administration of ECF had no effect on plasma AVP. We conclude that oropharyngeal factors account for temporary satiety and the rapid inhibition of vasopressin secretion.
Effects of glucose infusion on hepatic and muscle glycogenolysis in exercising dogs
Authors: Issekutz B.
Published: December 2017

Hepatic glucose production (Ra) and the rate of utilization of nonglucose sources (essentially muscle glycogen) were measured in dogs running on a treadmill (15%, 133 m/min) with indwelling catheters in the jugular vein and carotid artery. A mixture of [3-3H]glucose and [U-14C]glucose was used as tracer according to the principles of the primed constant-rate infusion techniques. Glucose was infused intravenously at a rate (12 mg.kg-1.min-1) about 20% higher than the endogenous glucose Ra in exercising dogs. Glucose infusion started either at the beginning of the run or midexercise. Plasma insulin (IRI), glucagon (IRG), and cAMP levels were measured. Exogenous glucose prevented the usual decline of both plasma glucose and IRI without causing hyperglycemia. Exercise increased the molar ratio of IRG/IRI from 0.7 to 1.4, and glucose infusion lowered it to the resting value. The rise of plasma cAMP was slowed significantly. Both the hepatic glucose Ra and intramuscular glycogenolysis were strongly inhibited and the metabolic clearance rate of glucose was increased by 60–100%. The ratio of the specific activities of [14C]lactate to [14C]glucose indicated that 75–95% of the lactate turnover arose from plasma glucose. The corresponding value in the control group was 40–50%. It is concluded that in prolonged exercise the decline of both plasma glucose and insulin play a major role in preserving glucose homeostasis, by limiting the glucose uptake of the working muscle and by helping to achieve an approximately equal contribution of the liver and the muscle glycogen for the elevated glycolysis.
LH responses to LHRH, DBcAMP, and 17 beta-estradiol in cultures derived from aged rats
Authors: Tang L. K. , Tang F. Y.
Published: December 2017

Effects of luteinizing hormone-releasing hormone (LHRH), N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAmP), and 17 beta-estradiol (E2) on LH responses were compared in 4-day-old pituitary cultures derived from female rats (Fischer 344) of 9 and 31 mo of age. Pituitary LH contents were similar in 5 X 10(5) freshly dispersed cells prepared from the two groups of rats. LH release in response to a 4-h incubation with 10 nM LHRH was virtually the same in cultures derived from 9- and 31-mo-old rats, 140 +/- 2 ng and 138 +/- 18 ng/4 h, respectively. In cultures derived from 9-mo-old rats, incubation with 8 mM DBcAMP for 4 h significantly stimulated LH release (286% of control level), and treatment with 10 nM E2 for 3 days significantly increased both basal LH release and LH accumulation (sum of LH contents in cells and medium) to 162 and 125% of control level, respectively. Neither DBcAMP nor E2 affected cultures derived from the 31-mo-old rats. These results indicate that there is a difference in the LH response to DBcAMP and E2 between cultures derived from 9- and 31-mo-old rats. The loss of pituitary responsiveness to DBcAMP and E2 and the loss of pituitary cyclicity in the aged female rat may be causally related.
Possible existence of a long-loop feedback system between FSH and inhibin in female rats
Authors: DePaolo L. V. , Anderson L. D. , Hirshfield A. N.
Published: December 2017

Experiments were designed in which peripheral plasma inhibin levels were presumably altered in an attempt to investigate an interdependency between pituitary follicle-stimulating hormone (FSH) and ovarian inhibin secretion. In the first study, unilateral ovariectomy (ULO) was performed on 4-day cycling female rats under ether anesthesia at 0800 h on diestrous day 1 (D1). Inhibin-like activity [FSH-inhibiting activity(FSH-IA)] in untreated ovarian venous plasma (OVP) collected from the remaining ovary was assessed by an in vitro pituitary bioassay system. Both plasma FSH levels and FSH-IA significantly increased between 4 and 12 h after ULO. Thereafter, plasma FSH declined between 12 and 32 h after ULO, whereas FSH-IA remained elevated during this same time interval. Compared to sham-operated rats, plasma FSH was significantly elevated 4, 12, and 24 h after ULO, whereas FSH-IA was statistically higher only at 32 h after ULO. In a second experiment, rats were injected with charcoal-treated porcine follicular fluid (PFF) on proestrus and estrus. Control rats received saline. The data indicate that increased plasma FSH levels on D1 in PFF-treated rats (FSH rebound) may be a consequence of reduced endogenous inhibin secretion on estrus. As well, return of FSH to control levels on D2 in PFF-treated rats may have resulted from an FSH-associated increase in FSH-IA on D1 and D2.
Resumption of prolactin secretion after dopaminergic inhibition: differential effects of dopamine and its agonists
Authors: Woolf P. D.
Published: December 2017

The recovery of prolactin (PRL) secretion following dopaminergic inhibition was studied in vitro using pituitary monolayer cultures. PRL secretion over 4 h was inhibited comparably by 10(-6) M dopamine (DA), 10(-7) M apomorphine (APO), and 10(-10) M bromocriptine (45%, 42%, 51%, respectively) with reciprocal increases in intracellular hormone content. After drug removal, the PRL secretion rate in the cultures that had been treated with DA was 208% of the control cultures by the 2nd h but returned to control values by 4 h, whereas the secretion rate after APO was 131–142% of control throughout the 4-h recovery period. In contrast, PRL secretion remained significantly less than control 20 h after the removal of bromocriptine. Although haloperidol (10(-7) M) prevented the inhibitory action of bromocriptine when added simultaneously, the addition of haloperidol did not restore PRL secretion when added in the posttreatment period. Thus, DA and APO inhibition of PRL release is readily reversible and is followed by early PRL hypersecretion. However, bromocriptine's effects are sustained and once started are not reversed by DA antagonists.
Effect of vitamin D sterols and dietary magnesium on calcium and phosphorous homeostasis
Authors: Levine B. S. , Walling M. W. , Coburn J. W.
Published: December 2017

Calcium (Ca) and phosphorus (P) metabolism were studied in vitamin D-deficient rats as vitamin D status and dietary magnesium (Mg) were varied. Rats given normal (0.03%) or high (0.2%) Mg diets received either vehicle, vitamin D3 (1,650 pmol/day), or 1,25-dihydroxyvitamin D3 (60 pmol/day) for 9 days. In vitamin D-deficient rats, high dietary Mg lowered intestinal Ca absorption from 40 +/- 5 to 11 +/- 5%; P absorption decreased 50%. Treatment with 1,25-dihydroxyvitamin D3 prevented the Mg-induced fall in absorption; vitamin D3 did so only for the first 6 days. The total Ca and Mg (Ca + Mg) absorbed (mM/day) decreased from 0.85 +/- 0.050 mM/day to 0.14 +/- 0.10 with the high dietary Mg; 1,25-dihydroxyvitamin D3 treatment raised Ca + Mg absorption regardless of diet Mg; high dietary Mg raised serum Ca despite a decreased intestinal Ca absorption and urinary Ca; treatment with either sterol had no added calcemic effect. These results are consistent with two processes for intestinal Ca and P transport: one vitamin D-dependent and the other non-vitsamin D-dependent and inhibited by high dietary Mg. Also high dietary Mg increases serum Ca, perhaps by affecting bone resorption.
Uterine blood flow and timing of blastocyst implantation in the guinea pig
Authors: Garris D. R. , Whitehead D. S.
Published: December 2017

The temporal and direct relationships between serum estradiol (E) and progesterone (P) levels and uterine blood flow (UBF) and intrauterine oxygen tension (IU PO2) were examined in guinea pigs between days 1 and 8 of pregnancy. Both UBF and IU PO2 were measured in situ using a noninvasive electromagnetic blood flow monitor and needle oxygen electrode, respectively. Serum P levels remained relatively constant throughout the first 8 days of pregnancy. In contrast, serum E levels declined to basal levels between days 1 and 3, and then subsequently rose between days 4 and 7 before again falling to basal levels by day 8. The changes in UBF and IU PO2 paralleled those of serum E levels, both exhibiting a rise between days 5 and 6. The direct effect of oil, E, or P injections on UBF and IU PO2 measurements in ovariectomized animals indicated that E induced a dramatic rise in both uterine parameters, whereas both measurements remained at basal levels after oil or P treatment. The results of this study indicate that UBF and IU PO2 levels are directly regulated by the cyclic fluctuations in serum E. The temporal relationship between the days 4 to 7 rise in serum E, UBF, and IU PO2 levels and the timing of blastocyst implantation suggest that these events are involved in uterine preparation for nidation in the guinea pig.
Regulation by catecholamines of spontaneous growth hormone secretion in the baboon
Authors: Stewart J. K. , Koerker D. J. , Goodner C. J. , Gale C. C. , Minton M. F. , Steiner R. A.
Published: December 2017

To gain an increased understanding of the role of central neurotransmitters in the regulation of spontaneous growth hormone (GH) secretion in the primate, we investigated the effects of peripheral intravenous infusion of the alpha-adrenergic receptor-blocking agent, phentolamine (5.0-mg bolus and 1.5 mg . kg-1 . 12 h-1), and the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (MPT, 300 mg . kg-1 . 24 h-1), on the pattern of GH secretion in five adolescent male baboons. Serum GH concentrations were measured in blood samples taken at 20-min intervals over 12 h (0530–1730) after an overnight fast. In nontreatment control studies, GH secretion exhibited a predictable rhythmic oscillation with a mean period of 5.7 +/- 0.4 (SE) h. Phentolamine significantly decreased the 12-h mean and integrated GH concentrations compared to control values, but the small peaks of GH, which could be distinguished from base-line concentrations in three of the animals, occurred at the same time as during control studies. Whereas alpha-methyl-p-tyrosine slightly reduced serum levels of GH, it significantly increased the GH pulse frequency in the baboons. A two- to fourfold increase in serum prolactin levels occurred in all animals treated with MPT. These findings suggest that alpha-adrenergic pathways play a stimulatory role in maintaining spontaneous daytime GH secretion in the baboon and that one or more catecholamines are involved in the generation of rhythmic GH release.
Characteristics of bovine parathyroid hormone extraction by dog liver in vivo
Authors: D'Amour P. , Huet P. M. , Segre G. V. , Rosenblatt M.
Published: December 2017

The metabolic fate of various 125I-labeled preparations of bovine parathyroid hormone (bPTH) during a single passage through the liver was studied in anesthetized dogs. Each 125I-bPTH preparation was injected in the portal vein with 131I-albumin and 99mTc-erythrocytes, two reference indicators. A dilution curve was obtained for each indicator by counting the radioactivity present in tubes collected by hepatic vein sampling. Hepatic blood flow (HBF) and fractional hepatic extraction (FHE) were calculated from these curves. Extraction results were further validated by comparing the gel chromotography profile of the 125I injected and of the 125I recovered. The FHE of 125I after an injection of 125I-bPTH-(1--84) was 32.75 +/- 9.39% (mean +/- SD; n = 23) for a mean HBF of 48.18 +/- 11.83 ml . kg-1 . min-1. The FHE was independent of the dose of hormone injected (0.34-812 ng) but was inversely related to the HBF (r = -0.6768, P less than 0.001). 125I was not extracted after an injection of 125I-bPTH-(1--34) ( n = 8) or of 125I-bPTH-(34/43--84) (n = 5). On the other hand, after an injection of 125I-bPTH-(28--48), 18.7 +/- 5.5% (n = 8) of the 125I was extracted for an HBF of 47.3 +/- 17.0 ml . kg-1 . min-1. Analysis of the gel chromotography profiles further disclosed that 7.6 +/- 4.2% of the 125I-bPTH-(1--84) injected was transformed into carboxyl terminal fragments; 13.1 +/- 2.6% of the 125I-bPTH-(28--48) and 20.9 +/- 4.9% of the 125I-bPTH-(1--34) injected were also cleaved into smaller molecular weight products. We conclude that the integrity of the sequence 28--48 is important for the FHE of 125I-bPTH-(1--84). Although nonsaturable, this process is inversely related to the HBF. Liver inactivation of intact PTH or of its fragments also proceeds through rapid cleavage into smaller molecular weight products.
FSH and testosterone effects in seminiferous tubules of immature hypophysectomized rats
Authors: Collins J. A. , Sepsenwol S. , Braun T.
Published: December 2017

The effects of follicle-stimulating hormone (FSH) and testosterone on the development of the cytosolic germ cell adenylate cyclase and germ cell morphology in rats hypophysectomized at 29 days of age were studied. Following hypophysectomy, the adenylate cyclase content fell to marginal levels and germ cell development ceased at the late pachytene stage. Testosterone treatment led to a moderate increase in the cytosolic enzyme content and to progression of spermatid cell development to stages 8–12. FSH treatment with doses of 80–100 micrograms/day restored enzyme content to levels seen in control rats, as well as progression of germ cell development up to stages 15–16, i.e., to the same stages present in age-matched control (sham-operated) rats. The results indicate that in immature rats FSH is essential for spermatid cell maturation as is evidenced by its ability to stimulate the formation of cytosolic germ cell adenylate cyclase to quantitatively normal levels, as well as to stimulate the development of spermatid cells.
Effects of sleep-promoting factor from human urine on sleep cycle of cats
Authors: Garcia-Arraras J. E.
Published: December 2017

Slow-wave sleep (SWS) and rapid-eye-movement sleep (REM) were recorded in cats for 32 h a) under control conditions, b) following intraventricular infusions of artificial cerebrospinal fluid (CSF), and c) following infusions of sleep-promoting factor S prepared from human urine (SPU). During the first 12 h after receiving artificial CSF, the cats slept 4.9 +/- 0.2 h in slow-wave sleep (SWS) and 1.4 +/- 0.1 h in REM. Similar values were obtained from the same cats under control conditions. After infusions of SPU, the duration of SWS in the same cats increased to an average of 6.9 +/- 0.5 h with no significant change in REM averaged over 12 h; a transient decrease of REM in the first 4 h was fully compensated in subsequent hours. The increased SWS induced by the sleep-promoting factor from human urine subsided after 12 h, and there was no compensatory increase in wakefulness during the subsequent 20 h. The normal sleep cycle was not affected. In cats, therefore, the primary effect of SPU is to increase normal SWS, with little effect on REM.
Abnormal brown adipose tissue in genetically obese mice (ob/ob): effect of thyroxine
Authors: Hogan S. , Himms-Hagen J.
Published: December 2017

Lean and genetically obese (ob/ob): mice were treated daily for 2 wk with thyroxine (T4), noradrenaline, or thyroxine plus noradrenaline. T4 treatment of obese mice increased the abnormally low binding of GDP to brown adipose tissue mitochondria and permitted a cold-induced increase to occur. It also brought about a return to a more normal ultrastructure of the mitochondria of the obese mice. T4 treatment did not alter the binding of GDP to brown adipose tissue mitochondria of lean mice. The binding of GDP to brown adipose tissue mitochondria is known to be to a 32,000-dalton polypeptide associated with the thermogenic proton conductance pathway. T4 treatment did not alter the proportion of this polypeptide in the mitochondrial membrane in either lean or obese mice. Treatment with noradrenaline did not alter the binding of GDP to brown adipose tissue mitochondria in either lean or obese mice. The effect of T4 is thought to be due to an improvement in the defective responsiveness of brown adipose tissue to endogenous noradrenaline in the obese mice, known to be related to their poor cold resistance and obesity. The improvement allows a more normal noradrenaline-induced unmasking of GDP binding sites, both in response to diet and in response to cold. Such treatment is known to improve cold resistance of the obese mice, and this appears to be correlated with an improvement in the functioning of their defective brown adipose tissue.
Hormonal activation of ornithine decarboxylase in embryonic chick pelvic cartilage
Authors: Burch W. M. , Lebovitz H. E.
Published: December 2017

We assessed whether hormones and metabolic factors known to stimulate anabolic processes in the embryonic chick pelvic cartilage would stimulate ornithine decarboxylase (ODC) activity. In vitro organ culture of these pelvic cartilages in time-course experiments with N(6)-monobutyryl cyclic AMP (BtcAMP), insulin, and 5% rat serum demonstrated maximal stimulation of ODC activity between 4 and 6 h with each factor. However, at 2 h insulin and serum significantly stimulated ODC activity (P less than 0.05) and BtcAMP did not. ODC was stimulated above control (100%) with the following factors: parathyroid hormone (PTH) (555 +/- 15%), BtcAMP (324 +/- 34%), 1-methyl-3-isobutylxanthine (MIX) (223 +/- 6%), prostaglandin E1 (PGE1) (227 +/- 15%), 3,3',5-triiodothyronine (T3) (184 +/- 22%), insulin (182 +/- 14%), multiplication-stimulating activity (MSA) (178 +/- 6%), 5% rat serum (253 +/- 57%). THe increase in ODC activity seen with BtcAMP and insulin was not due to a change in Km or a decreased rate of degradation of the enzyme. Actinomycin D (1 microgram/ml) inhibited stimulation of ODC activity by T3 and the cyclic AMP-mediated factors (PTH, BtcAMP, MIX, PGE1), but had only minimal effects on ODC stimulation by insulin, MSA, or serum. Amanitin inhibited both BtcAMP and T3 stimulation of ODC, but had no effect on insulin stimulation of ODC. Thus, hormones and metabolic factors known to stimulate anabolic processes in chick embryonic pelvic cartilage also increase ODC activity through at least two mechanisms: transcriptional (cyclic AMP-mediated and T3) and posttranscriptional (insulin, serum, MSA).
Evidence that TRH stimulates secretion of TSH by two calcium-mediated mechanisms
Authors: Geras E. J. , Gershengorn M. C.
Published: December 2017

Thyrotropin-released hormone (TRH) stimulation of thyrotropin (TSH) release from mouse thyrotropic tumor (TtT) cells is dependent on Ca2+. We demonstrate that TRH action in TtT cells does not require extracellular Ca2+ but that Ca2+ influx induced by TRH can augment TSH secretion. TRH caused a 46% increase in 45Ca2+ uptake by TtT cells in medium with 100 micro M Ca2+. The increment in 45Ca2+ uptake caused by TRH was dependent on the concentration of Ca2+ in the medium. In contrast to the effect of 50 mM K+, which also causes Ca2+ influx, TRH caused 45Ca2+ efflux and TSH release from TtT cells even when the concentration of Ca2+ in the medium was lowered below 100 micro M. TRH stimulated TSH release during perifusion in medium in which the free Ca2+ concentration was lowered to approximately 0.02 micro M, and reintroduction of Ca2+ into the medium simultaneously with TRH markedly increased TSH release. We suggest that TRH may affect Ca2+ metabolism in TtT cells by both extracellular Ca2+-independent and -dependent mechanisms and that this dual mechanism of action serves to augment further TSH secretion induced by TRH.
Insulin as a mediator of hepatic glucose uptake in the conscious dog
Authors: Cherrington A. D. , Williams P. E. , Abou-Mourad N. , Lacy W. W. , Steiner K. E. , Liljenquist J. E.
Published: December 2017

The aim of this study was to determine whether a physiological increment in plasma insulin could promote substantial hepatic glucose uptake in response to hyperglycemia brought about by intravenous glucose infusion in the conscious dog. To accomplish this, the plasma glucose level was doubled by glucose infusion into 36-h fasted dogs maintained on somatostatin, basal glucagon, and basal or elevated intraportal insulin infusions. In the group with basal glucagon levels and modest hyperinsulinemia (33 +/- 2 micro U/ml), the acute induction of hyperglycemia (mean increment of 120 mg/dl) caused marked net hepatic glucose uptake (3.7 +/- 0.5 mg . kg-1 . min-1). In contrast, similar hyperglycemia brought about in the presence of basal glucagon and basal insulin levels described net hepatic glucose output in 56%, but did not cause net hepatic glucose uptake. The length of fast was not crucial to the response because similar signals (insulin, 38 +/- 6 micro U/ml; glucose increment, 127 mg/dl) promoted identical net hepatic glucose uptake (3.8 +/- 0.6 mg . kg-1 . min-1) in dogs fasted for only 16 h. In conclusion, in the conscious dog, a) physiologic increments in plasma insulin have a marked effect on the ability of hyperglycemia to stimulate net hepatic glucose uptake, and b) it is not necessary to administer glucose orally to promote substantial net hepatic glucose uptake.
20 alpha-Hydroxysteroid dehydrogenase and 17 beta-estradiol dehydrogenase localize in cytosol of human term placenta
Authors: Strickler R. C. , Tobias B.
Published: December 2017

The 20 alpha-hydroxysteroid dehydrogenase activity in human term placenta has been localized by different investigators to nuclear, mitochondrial, microsomal, and cytosolic subcellular fractions. Furthermore, in the cytosol, 20 alpha-hydroxysteroid dehydrogenase activity may be a second function of the enzyme that mediates 17 beta-estradiol dehydrogenase activity. To search for a unique 20 alpha-hydroxysteroid dehydrogenase, human placental villous tissue, homogenized in three different buffer systems, was fractionated by differential centrifugation, and the 17 beta- and 20 alpha-activities were measured by radioisotope conversion assay. The enrichment and purity of the subcellular fractions were shown by marker enzyme assays and electron microscopy studies. Under all experimental conditions, 20 alpha-hydroxysteroid dehydrogenase activity was identified only in the 105,000 g placental cytosol: intact, osmotically ruptured, and acetone-extracted mitochondria, nuclei, and microsomes did not convert progesterone to 20 alpha-dihydroprogesterone. Furthermore, because 17 beta-estradiol dehydrogenase activity was in large part soluble in the cytosol, these localization studies are consistent with the hypothesis that the 20 alpha- and 17 beta-oxidoreductase activities in human placenta reside on one soluble protein.
Chronic sodium deficit in the immature rat: its effect on adaptation to sodium excess
Authors: Aviv A. , Kobayashi T. , Higashino H. , Bauman J. W. , Yu S. S.
Published: December 2017

The impact of chronic low-sodium intake during early development on body sodium homeostasis is not sufficiently known. To explore this effect, we have investigated the influence of chronic sodium deficit during the rapid growth period of rats (first phase, age 3-7 wk) and the short-term effect of sodium repletion (second phase, age 8-9 wk) on parameters such as growth rate, urinary aldosterone excretion, 22Na volume of distribution (space), and various renal functions. Three groups were studied: group I (control) and groups II and III. During the first phase the respective sodium intake values for these groups were 8.9, 3.1, and 1.5 meq.kg body wt-1.day-1. During the second phase, all groups had sodium intake of 8.7-8.8 meq.kg body wt-1.day-1. At the end of the first phase, group II showed weight gain and 22Na space values similar to those of group I. Group III demonstrated severe growth retardation and reduced 22Na space. During the second phase, both groups II and III demonstrated expansion of the 22Na space and persistently elevated urinary "acid-labile" aldosterone excretions. Despite the 2 wk of sodium repletion, group III failed to catch up with the body weight of groups I and II. It is concluded that chronic sodium deficit during early development transition is made to a higher sodium intake.
Glucocorticoids and hypothyroidism modulate development of fetal lung insulin receptors
Authors: Devaskar S. U. , Ganguli S. , Devaskar U. P. , Sperling M. A.
Published: December 2017

We investigated the development of insulin receptors in membranes of fetal rabbit lung during normal ontogeny and the effect of glucocorticoids and hypothyroidism. Specific binding of 125I-insulin to fetal lung membranes increased progressively to a peak at 29 days gestation, declining by 30 days. Scatchard plots were curvilinear and revealed a progressive increase in receptor numbers (X 10(10)/mg protein) from 129 +/- 7 (mean +/- SE) at 22-24 days to 575 +/- 16 at 29 days, declining to 467 +/- 12 at 30 days, term being approximately 31 days. Affinities did not change throughout gestation and were similar to those of adult lung; receptor numbers in adults were significantly lower than in fetuses at 26-30 days. Epinephrine and PGE1 could evoke a doubling of cAMP production in adult and fetal lung membranes until 29 days. Concomitantly with the fall in fetal insulin receptor number at 30 days, cAMP production in response to epinephrine or PGE1 increased fivefold. Induction of fetal hypothyroidism decreased insulin receptor numbers in the lung of the 28-day fetus by 70% from control (P less than 0.001) without a change in receptor affinity. In contrast, betamethasone administration increased fetal lung insulin receptor numbers by 250% (P less than 0.001) but did not alter their affinity; maternal lung insulin receptors were not altered. Thus, normal ontogeny of the fetal lung insulin receptor is characterized by a progressive increase in number followed by decline immediately before parturition associated with a sharp increase of cAMP responsiveness of the membranes. Hypothyroidism and glucocorticoid exposure can modulate the normal development of the fetal lung insulin receptor.
Osmolal effects on vasopressin secretion in the streptozotocin-diabetic rat
Authors: Van Itallie C. M. , Fernstrom J. D.
Published: December 2017

To determine the relationships between serum levels of arginine vasopressin (AVP) and serum osmolality and sodium in diabetic rats, we measured these variables in streptozotocin-diabetic and normal animals treated with water, isotonic saline, or hypertonic saline. Serum osmolality was higher and sodium lower in untreated diabetics than in controls; these variables increased in both groups after hypertonic saline. Serum AVP levels (measured by radioimmunoassay in Amberlite-extracted serum) were 2.3 +/- 0.5 and 9.8 +/- 1.7 pg/ml in control and diabetic rats, respectively, injected with isotonic saline. AFter injection of hypertonic saline, serum AVP levels rose to 14.5 +/- 2.3 pg/ml in controls and 18.7 +/- 1.7 pg/ml in diabetics. Water injection decreased serum AVP in diabetics (as in normals), but only to 5.8 +/- 1.0 pg/ml. To assess indirectly whether the chronically high levels of AVP in serum had an impact on kidney function, diabetic rats were studied after passive immunization with an anti-AVP serum. This treatment increased urine flow and decreased urine osmolality in dehydrated diabetic rats. Taken together, these data affirm in diabetic rats, as in humans, the occurrence of 1) elevated steady-state levels of AVP in serum; 2) abnormal sensitivity of AVP secretion to changes in serum sodium and osmolality; and 3) an apparently intact end-organ responsiveness to AVP.
Insulin action and resistance in obesity and noninsulin-dependent type II diabetes mellitus
Authors: Olefsky J. M. , Kolterman O. G. , Scarlett J. A.
Published: December 2017

Resistance to the action of insulin can result from a variety of causes, including the formation of abnormal insulin or proinsulin molecules, the presence of circulating antagonists to insulin or the insulin receptor, or defects in insulin action at the target tissue level. Defects of the latter type are characteristic of obesity and of noninsulin-dependent diabetes mellitus. Analysis of the nature of the insulin resistance in those disorders has been investigated in intact subjects with the use of the euglycemic glucose clamp technique, and both insulin receptors and insulin-mediated glucose metabolism have been studied in adipocytes and monocytes from affected individuals. In both conditions, the cause of insulin resistance is heterogeneous. In some, insulin resistance appears to be due to a defect in the insulin receptor, whereas others have a defect both in the receptor and at the postreceptor level. In both groups, more severe insulin resistance is due to the postreceptor lesion and is correctable with appropriate therapy.
Role of renin-angiotensin system in glucocorticoid hypertension in rats
Authors: Suzuki H. , Handa M. , Kondo K. , Saruta T.
Published: December 2017

The role of the renin-angiotensin system in the regulation of the blood pressure of dexamethasone-treated rats (Dex) was evaluated using saralasin, an angiotensin II antagonist, and SQ 14225 (SQ) (d-3-mercapto-2-methylpropranoyl-1-proline), an angiotensin-converting enzyme inhibitor. During a 7-day period blood pressure rose 65 +/- 10 mmHg (P less than 0.001) in Dex with no significant changes in plasma renin activity. Concurrent administration of dexamethasone and SQ attenuated the elevation of blood pressure (P less than 0.05). In the conscious, freely moving state, intravenous injection of SQ (10, 30, 100 micrograms/kg) reduced blood pressure of DEX in a dose-dependent manner (P less than 0.05). Also, intravenous injection of saralasin (10 micrograms.kg-1 . min-1) reduced blood pressure significantly (P less than 0.01). Bilateral nephrectomy abolished the effects of saralasin and SQ on blood pressure in Dex. These results indicate that the elevation of blood pressure in DEX depends partially on the renin-angiotensin system.
Mutations that affect membrane receptor for LDL are useful for studying normal receptor function
Authors: Anderson R. G.
Published: December 2017

Low-density lipoprotein (LDL), the major plasma cholesterol transport protein, is taken up by cells through a receptor-mediated process. After internalization through specialized segments of the cell surface called coated pits, the LDL is degraded in the lysosome and the released cholesterol is used by cells to meet various metabolic needs. The discovery of the LDL receptor and the studies of its function have provided new insights into both the biochemical aspects of cholesterol metabolism and the cell biology of receptor-mediated endocytosis. Of paramount importance in all of these studies has been the availability of human cells that express one or more allelic mutations that affect the function of the LDL receptor. These mutations have been valuable for assessing normal receptor function. Just as important, these mutations have been used as a reference point in the development of various cytochemical and biochemical techniques for studying receptor activity.
Syndromes of thyroid hormone resistance
Authors: Refetoff S.
Published: December 2017

Resistance to the action of thyroid hormone can involve both peripheral tissues and the pituitary (global resistance), the pituitary only or peripheral tissues alone. Global resistance is of variable severity and has been observed in more than 60 individuals, the majority occurring in 17 families. Affected subjects are commonly eumetabolic and have goiters, elevated plasma levels of total and free thyroxine and triiodothyronine, normal thyroid hormone metabolism, and normal serum TSH levels (albeit high for the corresponding levels of thyroid hormone). A variable degree of delayed bone maturation, mental retardation, learning disabilities, and hearing defects have been reported; and a variety of treatment regimens, most of which are aimed at reducing the level of plasma hormones and/or goiter, have been attempted before the correct diagnosis has been reached. The clinical disorder is equally common in males and females and appears to be due to one or more autosomal gene mutations. The causes for the hormone resistance may be heterogeneous, either influencing the receptor for thyroid hormones or some unidentified steps in hormone action. At present, the diagnosis is one of exclusion; no effective therapy is available, and all measures designed to lower serum thyroid hormone levels should be avoided.
Transport of alpha-keto analogues of amino acids across blood-brain barrier in rats
Authors: Conn A. R. , Steele R. D.
Published: December 2017

The transport of 14C-labeled alpha-keto acids across the blood-brain barrier (BBB) was studied in rats anesthetized with sodium pentobarbital using a modification of a single-injection dual-isotope technique. alpha-Keto acids were found to cross the BBB via a saturable carrier-mediated transport system that may be specific based on lack of inhibition by glucose, isoleucine, and ketone bodies on the uptake of tracer levels of 14C-labeled alpha-keto acids. alpha-Ketobutyrate and alpha-keto-gamma-methiolbutyrate, both straight chain keto acids, and alpha-ketoisocaproate, a branched-chain keto acid, appeared to cross the barrier by a common carrier based on cross-inhibition studies. Aromatic keto acids had no effect on the uptake of tracer levels of these 14C-keto acids. The Km of transport of alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate, was 0.11, 0.60, and 0.33 mM, respectively. The corresponding Vmax was 15.7, 73.3, and 30.2 nmol . g-1 . min-1. Phenylpyruvate was found not to cross the BBB. Inhibition of brain uptake of alpha-keto acids by propionate and pyruvate, and not by DL-beta-hydroxybutyrate suggests that alpha-keto acids and monocarboxylic acids are transported either via a common system independent of ketone bodies or share an affinity with a monocarboxylic acid and an alpha-keto acid transport system.
Isolated perfused Brockmann body as a model for studying pancreatic endocrine secretion
Authors: Ronner P. , Scarpa A.
Published: December 2017

The release of insulin, glucagon, and somatostatin was investigated in a newly developed in vitro perfusion preparation of the splenic Brockmann body (principal pancreatic islet) of the channel catfish (Ictalurus punctatus). The preparation was viable for up to 7 h by functional and morphological criteria. Glucose evoked a biphasic release of insulin and somatostatin, but had no effect on the release of glucagon. Arginine at basal glucose concentration caused a marked release of insulin and glucagon, but only a minor release of somatostatin.
Decreased rate of protein breakdown during nutritional recovery of mouse kidney
Authors: Bur J. A. , Conde R. D.
Published: December 2017

After a 5-day protein-depletion diet, there is a 23% decrease in kidney protein content in mice. When mice are shifted to a normal diet, protein mass is restored to its normal value 15 h after the nutritional change. The mechanism for this protein-depleted mice have a protein synthesis efficiency in vivo equal to 71% of that in normal kidneys, and normal values were reached within 6 h after the nutritional shift; 2) protein degradation rates were estimated either from the difference between the synthesis of kidney proteins and the net protein increase or by the disappearance of radioactivity from kidney proteins previously labeled by the administration of NaH14CO3 to mice. By both procedures, a large decrease in protein degradation rates during the recovery through a complete diet was observed.
Physiology of 24,25-dihydroxyvitamin D3 in normal human subjects
Authors: Kumar R. , Wiesner R. , Scott M. , Go V. L.
Published: December 2017

We determined the metabolic clearance and production rates of 24,25-dihydroxyvitamin D3 in four normal healthy adults. We also examined the excretion of radioactivity in stool, urine, and bile after the intravenous administration of 24,25-[3H]dihydroxyvitamin D3 to human subjects. 24,25-Dihydroxyvitamin D3 is rapidly cleared from the plasma with a half-life of approximately 390 +/- 25 min (mean +/- SE). The metabolic clearance rate of 24,25-dihydroxyvitamin D3 was 9.2 +/- 1.5 liters/day with a production rate of 26.4 +/- 7.2 micrograms/day (mean +/- SE). Within 1 day 13.0 +/- 4.2% (mean +/- SE) of the administered dose had appeared in the stool; by day 7, 48.8 +/- 2.7% of the dose had appeared in the feces. Within 24 hr, 6.4 +/- 0.8% of the administered dose appeared in the urine; 7.4 +/- 1.8% of the dose had appeared in the urine within 2 days. The biliary excretion of 24,25-dihydroxyvitamin D3 was studied in two subjects. By 8 h, 15.3 +/- 1.3% of the administered dose had appeared in the bile. The metabolites present in bile, feces, and urine were much more polar than 24,25-dihydroxyvitamin D3. These results demonstrate that 24,25-dihydroxyvitamin D3 is rapidly cleared from plasma and is excreted in the feces (probably via the bile) and urine of normal human subjects.
Interaction between amrinone and parathyroid hormone on bone in culture
Authors: Krieger N. S. , Stern P. H.
Published: December 2017

The cardiotonic agent amrinone has been postulated to directly affect Na-Ca exchange. Because stimulated bone resorption has been proposed to require Na-Ca exchange, we examined the effects of amrinone on bone. Amrinone inhibited release of Ca from neonatal mouse calvaria in organ culture stimulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin d3, or prostaglandin E2. Inhibition was dose dependent and maximal at 2 X 10(-4) M. The effect of amrinone differed from the inhibitory effects of calcitonin, ouabain, or nigericin in that 1) 6-h exposure to amrinone alone prevented the effect of subsequently added PTH; 2) amrinone was only partially effective if added after resorption was initiated by 24-h treatment with PTH; 3) coincubation with amrinone and PTH during the first 48 h of culture allowed for a response to PTH after amrinone was removed; no such protection by a stimulator occurred with ouabain or nigericin. Also submaximal concentrations of amrinone plus calcitonin, ouabain, or nigericin gave greater than additive inhibition of Ca release. Amrinone had no effect on basal bone cAMP or on the acute stimulation of cAMP by PTH. The results suggest that amrinone could have a more direct interaction with the pathway involved in stimulated bone resorption than the other inhibitors.
Effect of hypertonic intracarotid infusions on plasma vasopressin concentration
Authors: Wade C. E. , Bie P. , Keil L. C. , Ramsay D. J.
Published: December 2017

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.
Fatty acid and glucose utilization in isolated, working newborn pig hearts
Authors: Werner J. C. , Whitman V. , Vary T. C. , Fripp R. R. , Musselman J. , Schuler H. G.
Published: December 2017

The effects of exogenous fatty acids on glucose uptake were assessed in isolated, working newborn pig hearts in which great vessel pressures were controlled (mean 55 mmHg) and oxygenated nutrient buffer was recirculated through the heart for 30 or 60 min. When palmitate (1.5 mM) or octanoate (1.0 mM) were added to buffer containing 10 mM glucose and 100 mU insulin/ml, glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed to less than one-half that observed when glucose alone was present. Increased tissue levels of glucose 6-phosphate, fructose 6-phosphate, and citrate following perfusion in the presence of exogenous fatty acids were consistent with decreased glycolytic activity due to inhibition of phosphofructokinase. Measurements of carnitine in perfused and unperfused hearts indicated that total carnitine levels in neonatal hearts are similar to those of adult pigs. Increased tissue levels of long-chain acyl carnitine, acetyl carnitine, and citrate in hearts perfused with palmitate and glucose in combination with extensive fatty acid uptake and marked suppression of glycolysis indicated that the newborn pig heart is capable of utilizing fatty acids as a primary energy source.
Development of gluconeogenesis in isolated hepatocytes from the rabbit
Authors: El Manoubi L. , Callikan S. , Duee P. H. , Ferre P. , Girard J.
Published: December 2017

Gluconeogenesis from 10 mM lactate has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. Gluconeogenesis proceeds to a very low rate in fetal rabbit hepatocytes despite substantial activities of all gluconeogenic enzymes including mitochondrial phosphoenolpyruvate carboxykinase. A tenfold increase in the rate of gluconeogenesis occurs in hepatocytes from 1- or 2-day-old fasting or suckling newborn rabbits. The emergence of gluconeogenic capacity in newborn rabbit hepatocytes is triggered by birth itself and not by a chronological factor, and it is primarily controlled by an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase. Moreover, an active fatty acid oxidation is essential to support a high rate of gluconeogenesis in hepatocytes from newborn rabbits.
Stimulation of renin secretion by alpha-adrenoceptor agonists
Authors: Blair M. L.
Published: December 2017

This study was designed to determine whether stimulation of intrarenal alpha-adrenoceptors can increase renin secretion rate (RSR) in the absence of increased renal vascular resistance and to identify the accompanying changes in renal function. Experiments were performed in pentobarbital-anesthetized dogs in which renal perfusion pressure was maintained at approximately 90 mmHg and the infused kidney was acutely denervated. Renal artery infusion of the alpha-adrenoceptor agonist methoxamine (0.5 microgram X kg-1 X min-1 for 30 min) increased RSR from 160 +/- 95 to 1,376 +/- 385 ng ANG I/min (P = 0.01) but did not decrease renal blood flow (RBF); the same dose infused intravenously had no effect on RSR or RBF. Intra-arterial phenylephrine infusion (0.5 microgram X kg-1 X min-1 for 9 min) increased RSR by 500 +/- 157 ng ANG I/min (P less than 0.01) and decreased both inulin clearance (Cin) and urinary sodium excretion (UNaV) by 25% but did not affect RBF. At a lower concentration of phenylephrine (0.2 microgram X kg-1 X min-1 for 9 min), RSR increased by 318 +/- 103 ng ANG I/min (P less than 0.01) and RBF, Cin, and UNaV did not change. The increase in RSR was completely blocked by prazosin but was unaffected by propranolol. In summary, renin secretion can be stimulated by activation of intrarenal alpha-adrenoceptors even in the absence of increased renal vascular resistance.
Renal venous outflow and urinary excretion of norepinephrine, epinephrine, and dopamine during graded renal nerve stimulation
Authors: Kopp U. , Bradley T. , Hjemdahl P.
Published: December 2017

The effect of renal nerve stimulation (RNS) on renal venous outflow and urinary excretion of endogenous norepinephrine, epinephrine, and dopamine was examined in anesthetized dogs. In the unstimulated denervated kidney, there was a negative venoarterial concentration difference for all catecholamines. Low-level RNS (LLRNS) caused small changes in renal hemodynamics and renal venous outflow of dopamine and increased norepinephrine outflow by 3.22 +/- 0.95 pmol X min-1 X g-1 (n = 5, P less than 0.05). High-level RNS (HLRNS) reduced renal blood flow by 50% and increased renal venous outflow of norepinephrine and dopamine by 9.58 +/- 0.67 and 0.46 +/- 0.05 pmol X min-1 X g-1, respectively (n = 27, P less than 0.01 for both). Renal uptake of epinephrine was unchanged by HLRNS. The urinary excretion of norepinephrine but not dopamine was increased to a similar degree following RNS at both levels. HLRNS caused a similar increase of the urinary norepinephrine excretion from the contralateral denervated and unstimulated kidney. This could be explained by the increase in arterial norepinephrine (from 0.74 +/- 0.08 to 1.20 +/- 0.14 nM, P less than 0.01) caused by HLRNS as shown by experiments with intravenous infusions of norepinephrine. The alpha-adrenoceptor antagonist phenoxybenzamine counteracted the hemodynamic response to HLRNS and enhanced the renal venous outflow and urinary excretion of norepinephrine and dopamine. Our results indicate that renal nerves release dopamine as well as norepinephrine and that urinary catecholamine excretion is a poor indicator of intrarenal catecholamine release.
Inhibition of bone resorption in tissue culture by H1-receptor antagonists
Authors: Goldhaber P. , Rabadjija L.
Published: December 2017

Mouse bone culture studies show that several representative H1-receptor antagonists, promethazine hydrochloride, pyrilamine maleate, tripelennamine hydrochloride, and diphenhydramine hydrochloride, inhibit parathyroid extract-stimulated bone resorption. The H2-receptor antagonists, metiamide and cimetidine, are ineffective. In view of the finding that histamine and histamine agonists did not stimulate bone resorption, it is unlikely that histamine receptors are involved in mediating parathyroid extract-stimulated bone resorption. Because H1-receptor antagonists bind to phospholipids and have been shown to influence membrane structure and function, it is suggested that they inhibit bone resorption by a mechanism that depends on their membrane-stabilizing effect.