Decrease In Rate Of Synthesis Research Articles

Modulation of fatty acid synthesis in vivo in brown adipose tissue, liver and white adipose tissue of cold-acclimated rats.

The present experiment was an appraisal of the relative importance of fatty acid synthesis in brown adipose tissue (BAT) in young 28 or 5 degrees C adapted rats (9 weeks old). With a low-fat diet in vivo incorporation of 3H2O into BAT fatty acids was 8 times lower during the day than during the night and was not modified by a 6-hour fast during the day (28 degrees C). Cold acclimation doubled (night) or increased 8 times (day) BAT lipogenesis. Fasting led to a halving of the diurnal rate. A high-fat diet led to large decrease in synthesis rate during the night but had a weak effect on diurnal synthesis. The specific activity of fatty acids was 3 times lower in phospholipids than in neutral lipids. A comparison between 9- and 15-week-old rats indicated that in older warm-adapted rats BAT lipogenesis decreased by half but that cold stimulation was unaltered. These results were compared with hepatic and epididymal white adipose tissue lipogenesis. In conclusion, we showed that BAT of 5 degrees C rats is an important but not the major site for the conversion of carbohydrate to fat and that the proportional involvement of each tissue is age-dependent.

1 alpha,25-Dihydroxyvitamin D-induced modification of a cytosolic protein in embryonic chick intestine.

Two-dimensional electrophoresis together with radiolabeling experiments was used to examine cytosolic proteins of embryonic chick duodenum for responses to 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 caused a striking decrease in [3H]leucine content of an 18,000-dalton protein (approximate pI, 5.1) after a 10-min pulse with radioisotope followed by a 4-h chase. Decreased [14C]leucine content of the same protein was also observed at various times following 1,25-dihydroxyvitamin D3 addition to culture media; a significant decrease in radiolabel incorporation occurred within 30 min after addition of the hormone. The results argue that 1,25-dihydroxyvitamin D3 causes either a decreased synthesis rate or a post-translational modification of this protein. This change joins the biosynthesis of calcium-binding protein as an early event in the response of chick embryonic intestine to 1,25-dihydroxyvitamin D3.

Effect of cortisol on the synthesis of lamellar body glycerophospholipids in fetal rabbit lung tissue in vitro

The effect of cortisol on the rate of choline incorporation into tissue phosphatidylcholine was investigated in lung explants from fetal rabbits of 19–28 days gestational age. The explants were incubated in medium with or without fetal calf serum for up to 7 days. When lung tissues were incubated in serum-free medium, a stimulatory effect of cortisol on tissue phosphatidylcholine synthesis was found in explants from 21-, 24-, 26- and 28-day fetal rabbits; a stimulatory effect of cortisol was observed in 19-day fetal lung explants only if fetal calf serum was present in the culture medium. To assess directly the effect of cortisol on the synthesis of lamellar body phosphatidylcholine, choline incorporation into phosphatidylcholine associated with a purified lamellar body fraction isolated from lung explants of 21- and 28-day fetal rabbits was also investigated. Cortisol caused a marked stimulation of synthesis and accumulation of lamellar body phosphatidylcholine in lung explants from both 21- and 28-day fetal rabbits. The magnitude of the stimulatory effect of cortisol on the rate of synthesis of lamellar body phosphatidylcholine was always greater than the effect of cortisol on the rate of choline incorporation into lipids of tissue homogenates. The relative rates of synthesis of lamellar body phosphatidylinositol and phosphatidylglycerol were also significantly altered in lung explants from 21- and 28-day fetal rabbits by cortisol treatment. Lamellar bodies that were formed initially in the fetal lung explants were enriched in phosphatidylcholine and phosphatidylinositol and had a relatively low phosphatidylglycerol content. With cortisol treatment there was a decrease in the relative rate of synthesis of lamellar body phosphatidylinositol and an increase in the relative rate of synthesis of phosphatidylglycerol. The stimulatory effect of cortisol on the synthesis of lamellar body phosphatidylcholine was observed at an earlier time-point of incubation than was the effect of cortisol on the relative rates of synthesis of lamellar body phosphatidylinositol and phosphatidylglycerol. The temporal sequence of the cortisol-induced changes in the synthesis of lamellar body glycerophospholipids, therefore, reflects that which occurs with maturation in vivo.

Pre- and post-natal growth and protein turnover in smooth muscle, heart and slow- and fast-twitch skeletal muscles of the rat

The growth of one smooth and three individual striated muscles was studied from birth to old age (105 weeks), and where possible during the later stages of foetal life also. Developmental changes in protein turnover (measured in vivo) were related to the changing patterns of growth within each muscle, and the body as a whole. Developmental growth (i.e. protein accumulation) in all muscles involved an increasing proportion of protein per unit wet weight, as well as cellular hypertrophy. The contribution of the heart towards whole-body protein and nucleic acid contents progressively decreased from 18 days of gestation to senility. In contrast, post-natal changes in both slow-twitch (soleus) and fast-twitch (tibialis anterior) skeletal muscles remained reasonably constant with respect to whole-body values. Such age-related growth in all four muscle types was accompanied by a progressive decline in both the fractional rates of protein synthesis and breakdown, the changes in synthesis being more pronounced. Age for age, the fractional rates of synthesis were highest in the oesophageal smooth muscle, similar in both cardiac and the slow-twitch muscles, and lowest in the fast-twitch tibialis muscle. Despite these differences, the developmental fall in synthetic rates was remarkably similar in all four muscles, e.g. the rates at 105 weeks were 30-35% of their values at weaning. Such developmental changes in synthesis were largely related to diminishing ribosomal capacities within each muscle. When measured under near-steady-state conditions (i.e. 105 weeks of age), the half-lives of mixed muscle proteins were 5.1, 10.4, 12.1 and 18.3 days for the smooth, cardiac, soleus and tibialis muscles respectively. Old-age atrophy was evident in the senile animals, this being more marked in each of the four muscle types than in the animal as a whole. In each muscle of the senile rats the protein content and composition per unit wet weight, and both the fractional and total rates of synthesis, were significantly lower than in the muscles of younger, mature, animals (i.e. 44 weeks). In the soleus the decreased synthesis rate appeared to be related to a further fall in the ribosomal capacity. In contrast, the changes in synthesis in the three remaining muscles correlated with significant decreases in the synthetic rate per ribosome.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of compartmentalization of epinephrine in the regulation of phenylethanolamine N-methyltransferase synthesis in rat adrenal medulla.

The mechanism of regulation of phenylethanolamine N-methyltransferase (PNMT) in rat adrenal medulla after hypophysectomy and dexamethasone treatment was studied. The activity, amounts, and rates of synthesis and degradation of PNMT were measured in explants of adrenal medullae from sham-operated, hypophysectomized, and hypophysectomized-dexamethasone-treated rats. The storage, uptake, and catabolism of [3H]epinephrine were also measured in these three groups to determine any alteration in the granular vs. extragranular compartmentalization of epinephrine induced by these procedures. In addition, the effect of epinephrine on the rate of the enzyme's synthesis and degradation in cultured explants of medullae was measured. The results indicate that the 40% decrease in the amount of PNMT 1 month after hypophysectomy is due to a 28% decrease in the specific rate of synthesis of this enzyme. Dexamethasone treatment restores both the rate of synthesis of the enzyme and the amount of this enzyme found in the tissue to control levels. Our studies show that there is a 73% increase in uptake of [3H]epinephrine into medullary explants from hypophysectomized rats compared to controls. Fifty-six percent of this [3H]epinephrine was converted to metabolites in both groups, indicating that hypophysectomy produced no change in the rate of catabolism. However, uptake of [3H] epinephrine into medullary storage granules from hypophysectomized rats was decreased by 50%. These studies on the uptake, storage, and catabolism indicate that hypophysectomy favors conditions that increase levels of extragranular epinephrine. This altered compartmentalization is reversed by dexamethasone treatment, which decreases the uptake and increases the binding of epinephrine. Epinephrine added to cultured tissue decreased the rate of biosynthesis of PNMT by 22%, an extent similar to that observed after hypophysectomy. It is concluded that the effect of hypophysectomy on this enzyme is mediated by epinephrine.

Synthesis of a shortened pro-alpha 2(I) chain and decreased synthesis of pro-alpha 2(I) chains in a proband with osteogenesis imperfecta.

Synthesis of type I procollagen was examined in skin fibroblasts from a proband with a lethal variant of osteogenesis imperfecta. The fibroblasts synthesized shortened pro-alpha 2(I) chains and these shortened chains accounted for all the pro-alpha 2(I) chains synthesized by the cells. In addition, there was a decrease in the relative rate of synthesis of pro-alpha 2(I) chains. Fragmentation of the shortened pro-alpha 2(I) chains with vertebrate collagenase and cyanogen bromide demonstrated that the shortening was in alpha 2(I)-CB3,5A, a fragment from about the middle of the chain containing amino acid residues 361 to 775. Based on the relative mobility in electrophoretic gels, the shortening was about 20 amino acid residues. The decreased synthesis of pro-alpha 2(I) chains was demonstrated by an increase in the ratio for the rates of synthesis of pro-alpha 1(I):pro-alpha 2(I) chains. It was associated with an increase in the ratio of mRNAs for pro-alpha 1(I):pro-alpha 2(I) in the cells. Fibroblasts from the father also demonstrated a decreased synthesis of pro-alpha 2(I) chains as reflected by an increase in the ratio of newly synthesized pro-alpha 1(I):pro-alpha 2(I) chains. No shortened pro-alpha 2(I) chains were seen in fibroblasts from either the father or the mother. The observations suggested that the proband inherited a nonfunctioning pro-alpha 2(I) gene from her father and that the gene for the shortened pro-alpha 2(I) chain probably arose from a sporadic mutation.

Amino acid transport and crystallin synthesis in the bovine lens

Bovine lenses were incubated in a defined, bicarbonate-free culture medium (EMEM) and the kinetics of amino acid uptake and protein synthesis investigated. The kinetics were interpreted in terms of a simple multi-compartment model. [ 14C]tyrosine was found to be totally exchangeable in the incubated lens and the rate constant for the exponential increase in activity was 0·0175 hr −1. The rate of influx was markedly reduced by incubating in the presence of ouabain (10 −5 m), which also caused a concomitant disturbance of the normal sodium and potassium distributions. The soluble proteins from the ineubated lenses were fractionated on Sephadex G-200 and the rate of incorporation into the crystallins was shown to fall into two classes. The rate of synthesis of α and β L crystallin was relatively rapid (rate constants approximately equal to 0·004 hr −1), while the synthesis rates of β H and β S γ were both much slower (0·001 hr −1). The efflux kinetics of [ 14C]tyrosine were determined and the rate of decrease of the free amino acid pool was identical to the rate of increase determined from an influx experiment. Hence the lenses are in a steady state with respect to free tyrosine throughout the incubation period (up to 160 hr). All classes of proteins continued to be synthesized during efflux experiments and there was no evidence for a breakdown of α or β L crystallin during the time-course of these experiments. Ouabain slowed the rate of loss of tyrosine from the free amino acid pool, and this was interpreted in terms of an ouabain-induced decrease in synthesis rate rather than as a decrease in efflux rate from the lens. There was in fact a very marked decrease in the incorporation of [ 14C]tyrosine into the α and β L crystallins on exposure to ouabain, and this decrease was apparent before and change in activity in the amino acid pool.

Effect of corticosterone on myofibrillar protein turnover in diabetic rats as assessed by Ntau-methylhistidine excretion.

The effect of corticosterone on myofibrillar protein breakdown in diabetic rats was investigated in order to assess the possible counteracting effects of the secondary rise in plasma insulin concentrations which normally accompanies such treatment. N(tau)-Methylhistidine excretion, an index of myofibrillar protein breakdown, was compared before and after corticosterone treatment (4.0 mg/100 g body wt. per day) of normal control, adrenalectomized, 10-day-streptozotocin-diabetic and adrenalectomized diabetic rats. Diabetic rats received 1.5 units of insulin/100 g body wt. per day throughout the experiment and showed marked hyperglycaemia and glucosuria during corticosterone treatment, whereas non-diabetic rats had only mild hyperglycaemia but elevated insulin concentrations. Corticosterone treatment increased the average rate of myofibrillar protein breakdown by 68% and 95% respectively in non-diabetic and diabetic rats. Net loss of muscle non-collagen protein for the same 7-day period was greater in diabetic than in non-diabetic animals (4.15 versus 2.84% per day), and the calculated average synthesis rates were lowest in diabetic rats. Adrenalectomy had little effect except to decrease slightly the rate of muscle protein breakdown. These results show that the rise in plasma insulin concentrations that accompanies exogenous corticosterone administration to non-diabetic rats diminishes the catabolic effect of this glucocorticoid on muscle. Insulin appears to antagonize the effects of the glucocorticoid by attenuating the increased rates of myofibrillar protein breakdown and, to a lesser extent, by limiting the decrease in synthesis rates.

Studies on the effect of indomethacin and sulfinpyrazone on the rates of synthesis of albumin and acute-phase α 1-acid glycoprotein by rat liver slices

The rates of synthesis of albumin and α 1-acid glycoprotein were determined in the presence of indomethacin and sulfinpyrazone. There were significant reductions in synthesis rates of both proteins in the presence of concentrations of 0.5 m m or greater in the case of both drugs tested. Incorporation studies showed that decreased synthesis rates were accompanied by inhibition of incorporation of radioactive precursors into albumin and α 1-acid glycoprotein and into total protein isolated from liver and incubation medium. Incorporation of [ 3H]orotic acid into liver RNA was also subject to inhibition by the drugs used in the present work as well as by salicylate and phenylbutazone, two drugs used in an earlier study. Synthesis of RNA followed by orotic acid incorporation was more sensitive to inhibition by the four drugs in question; substantial inhibition was observed in the presence of 0.25 m m or greater of indomethacin, sulfinpyrazone, and phenylbutazone, and in the presence of 2 m m or greater of salicylate.

Inhibition of dihydrofolate reductase gene expression following serum withdrawal or db-cAMP addition in methotrexate-resistant mouse fibroblasts

We have used a methotrexate (MTX)-resistant mouse 3T6 cell line (M50L3), that overproduces dihydrofolate reductase (DHFR) and its mRNA by a factor of 300, to study the mechanism for turning off DHFR gene expression following withdrawal of serum factors or elevation of the intracellular level of cAMP. When resting (G0) M50L3 cells are serum-stimulated to reenter the cell cycle, the level of DHFR activity begins to increase at about the same time the cells begin synthesizing DNA. The increase in enzyme activity is preceded by increases in the synthesis rate of the enzyme, and the content and production rate of DHFR mRNA. These increases, as well as entry into S phase, are blocked when the cells are serum-stimulated in the presence of dibutyryl cyclic AMP (db-cAMP) and theophylline. In this study, we found that when these drugs were added, or the serum stimulus was withdrawn during S phase (20 h following stimulation), the subsequent increase in DHFR level was blocked. Immunoprecipitation of DHFR from pulse-labelled cells showed that both treatments led to a rapid decrease in synthesis rate of the enzyme. The effect on total protein synthesis was much less than on DHFR synthesis. In DNA-excess filter hybridization experiments, we found that the content of cytoplasmic DHFR mRNA decreased in parallel with the synthesis rate of the enzyme. This was due in part to a decrease in the production rate of DHFR mRNA relative to total mRNA. In addition, drug addition or serum withdrawal led to a significant destabilization of DHFR (as well as total) mRNA. About 85% of poly(A)(+) DHFR mRNA was associated with polysomes in resting, growing, or cAMP-treated cells, suggesting that DHFR gene expression was not controlled at the translational level under these conditions.

Effects of peptide hormones on urea- and glycogen-synthesis of isolated hepatocytes and the influence of a toxic factor from burnt mouse and human skin.

A toxic extent has been isolated and partially purified from burnt human and mouse skin and also from sera of severely burnt patients, which causes disturbances of energy metabolism and decreased synthesis rates for glucose and urea in the perfused rat liver. Enzymatically isolated hepatocytes from rat livers were used to study the toxic effects on hormonal sensitivity, synthetic functions and ultrastructure of the cells. A decreased synthesis of urea and glycogen was found in cells from rats treated 5 days before with "toxin" and in cells, which were directly incubated with the toxic factor. Glucagon increased urea synthesis in normal cells by 33%, and a decrease of 25% was caused by insulin. Cells of rats treated with the nontoxic precursor of the toxic factor from normal skin were similar, while those treated with "toxin" produced less urea and did not react to glucagon or insulin. Glycogen synthesis was reduced in cells directly incubated with the "toxin", however, the hormonal effects were still observed. Surface alterations of "toxin" treated cells and cells of "toxin" treated rats were found by scanning electronmicroscopy. These findings provide evidence of a direct cytotoxic effect of the toxic factor from burnt skin. It is proposed that the "toxin" acts on the cellular membrane with destruction of surface and receptorproteins.

Studies on the effect of phenylbutazone and salicylate on the rates of synthesis of albumin and acute-phase α1-acid glycoprotein by rat liver slices

Rates of synthesis of albumin and α 1-acid glycoprotein were determined in presence of phenylbutazone and salicylate using liver slices prepared from control and experimentally inflamed rats. The rates of synthesis in control and experimental liver slices were 50 and 35 μg/g wet wt slices per hour, respectively, for albumin and 9.5 and 24 μg/g wet wt slices per hour, respectively, for α 1-acid glycoprotein. There were significant reductions in synthesis rates of both proteins in presence of concentrations of 0.5 m m or greater of phenylbutazone or concentrations of 2 m m or greater of salicylate. Incorporation studies showed that decreased synthesis rates were accompanied by inhibition of incorporation of radioactive precursors into albumin and α 1-acid glycoprotein and into total protein isolated from liver and incubation medium.

Synthesis of proteins and RNA of the 60S ribosomal subunit in HeLa cells recovering from valine deprivation

The synthesis of ribosomes in HeLa cells was studied during recovery from a 20-hour deprivation for valine. The rates of incorporation of labeled precursors into ribosomal pre-RNA, processed rRNA, total cellular proteins, and proteins of the 60S ribosomal subunit returned to normal or nearly normal levels immediately after restoration of valine to the medium. Specific proteins of the 60S ribosomal subunit, whose apparent net synthesis is reduced more than that of the other proteins of the 60S ribosomal subunit during valine deprivation, were no longer undersynthesized after valine was restored. This rapid recovery suggests that the apparent decrease in the net rate of synthesis of these ribosomal proteins during valine deprivation is effected at the translational or post-translational level. No evidence of significant synchrony in any particular stage of the cell cycle was observed after a 20-hr valine deprivation.

POLYNEUROPATHIES AND CNS PROTEIN METABOLISM

A defect in neuronal protein metabolism has been proposed as one of the primary, molecular events underlying the development of polyneuropathies of the dying back type. Using acrylamide-intoxication as an experimental model to study these polyneuropathies, changes in leucine-incorporation into proteins disability. Proteinsynthesis rates were determined in vivo using flooding concentrations of [1-14C]valine as the precusor. Under conditions of acute and of chronic intoxication, a decrease in synthesis rate was measured preceding the loss of functional ability. Similar changes in protein synthesis rate were observed in peripheral tissues such as heart muscle and liver showing the general toxicity of acrylamide. Methylene bisacrylamide, that was used to discriminate between the neurotoxic action of acrylamide and its systemic effects, interfered with protein synthesis rates in a comparable way. No change in protein synthesis rate was observed under in vitro conditions suggesting that the interference of acrylamide with the synthetic machinery for protein synthesis in vivo is mediated by one or more as yet unknown indirect factors.

Effects of anisomycin and CNS stimulants on brain catecholamine synthesis

Mice were injected with anisomycin, an inhibitor of cerebral protein synthesis; d-amphetamine, strychnine, or caffeine was administered 30 min later. Fifteen min before sacrifice at 1 or 2 hr after injection of anisomycin, 3H-tyrosine was injected intravenously, and catecholamine synthesis rates were estimated by measurement of the specific activity of 3H-tyrosine and the accumulation of 3H-norepinephrine and 3H-dopamine. Anisomycin decreased synthesis rates of catecholamines, but this effect was not significantly affected by any of the CNS stimulants. These results suggest that the recently reported reversal of anisomycin-induced amnesia by these stimulants is not due to an attenuation of brain catecholamine synthesis inhibition.

Induction of murine erythroleukemia differentiation by actinomycin D

Murine erythroleukemia cells are induced to differentiate by 0.5-5 ng of actinomycin D per ml. Murine erythroleukemia cells cultured with actinomycin D prolong cell doubling time but achieve the same density after 5 days as cells without inducer. Actinomycin D causes over 95% of the cells to become benzidine-reactive. [(3)H]Actinomycin D uptake into DNA can be detected within 2 hr and reaches a maximum (approximately 0.1 pmol/10(6) cells) by 10-12 hr. It is estimated that about one out of 10(5) dG.dC pairs is bound to actinomycin D. Commitment to differentiation, assayed by transfer of cells to culture without inducer, was detected as early as 5 hr. Unlike Me(2)SO, which causes a transient prolongation in G(1) at about 15-20 hr, cells cultured with actinomycin D show a more sustained increase in the proportion of the cells in G(1). Globin mRNA accumulation was detectable by 19 hr in culture. Alteration in DNA stability in alkaline sucrose gradients was detected by 19 hr. Actinomycin D induces synthesis of Hb(maj) and Hb(min) in approximately equal amounts. A decrease in rates of synthesis of RNA, DNA, and total protein occurs in cells cultured with actinomycin D, as well as in cells cultured with Me(2)SO. No evidence for an early action of actinomycin D at the plasma membrane was obtained by measurement of changes in cell volume or (86)RbCl uptake. Taken together, the present results indicate that actinomycin D is a potent inducer of differentiation of murine erythroleukemia cells and suggest that the target of its effect may be at the level of DNA.

Measurements of in vivo rates of protein synthesis in brain, spinal cord, heart and liver of young versus adult rats, intact versus hypophysectomized rats.

Abstract— In vivo protein synthesis rates in rats were estimated by single i.p. injections of large quantities of [1‐14C]valine. This method gives reliable estimates of the precursor specific activity and average protein synthesis rates. In the brain, spinal cord, heart and liver, the average rates for adults were 0.65, 0.42, 0.49 and 1.92% replacement of protein‐bound amino acid per h. In the brain and liver of 10‐day olds the average rates were estimated to be 1.46 and 3.12% per h respectively. Hypophysectomy decreased synthesis rates by 25% or more in all tissues studied. The disadvantages of the method are that applying large amounts of valine i.p. appeared to constitute a stress and that the valine solution required for injection was hypertonic, causing withdrawal of body fluids of the animal.

Effects of a large dose of oestradiol on antithrombin III metabolism in male and female dogs

Abstract. Canine antithrombin III (AT) metabolism was studied in twenty healthy dogs of both sexes first under control conditions, using 125I‐AT as a tracer, then, in the same dogs after 20 mg oestradiol intramuscularly and another 20 mg 7 days later. Under control conditions the plasma AT concentration and the amount of plasma AT (x̄) were greater in males than females. The plasma half‐lives of 125I‐AT averaged 2.14 ± 0.09(SD) days in males and 1.97 ± 0.05(SD) days in females and were significantly different. The fractional catabolic rate of plasma AT (j3p) was lower in males than in females, but the amount of plasma AT catabolized (j3pX̄) (synthesis rate) was not significantly different (averaging 20 ± 3.7 (SD) in males and 18 ± 2.2(SD) mg/kg/day in females). The total body AT (x̄+ȳ) was greater in males than in females; average values 55 ± 7.5(SD) and 46 ± 5.2(SD) mg/kg, respectively. Under the influence of oestradiol, the plasma AT concentration and AT(x̄) decreased in both sexes, but the plasma half‐lives of 125I‐AT showed no appreciable changes. The values of AT(j3p) and AT(j3pX̄) were significantly decreased in both sexes; average values of the latter being 14 ± 1.5(SD) in males and 12 ± 2.2(SD) mg/kg/day in females. AT(x̄+ȳ) averaged 43 ± 3.8(SD) in males and 33 ± 6.3(SD) mg/kg in females and were significantly decreased. These results indicate that the decreased values in plasma AT concentration, x̄ and x̄+ȳ following oestradiol administration are due to the decreased synthesis rate of AT and not to an increased catabolic rate.

Effects of estrogen on dopamine turnover, glutamic acid decarboxylase activity and lordosis behavior in septal lesioned female rats

Estradiol benzoate (EB) treatment (2.0 μg/day × 3) of septal lesioned adult female rats produces a marked increase in lordosis behavior over similarly treated sham operated animals. In these animals endogenous dopamine (DA) and norepinephrine (NE) levels were measured and turnover rates were estimated following tyrosine hydroxylase inhibition with α-methyltyrosine, in both EB and oil (0.05 ml × 3 days) treated groups. No consistent pattern of change in the level or rate of turnover of NE was noted for any of the treatment groups. No differences in either the level or turnover of DA were seen in the oil treated septal lesioned group, relative both to EB and oil treated sham operated groups. However, in the amygdala, corpus striatum and nucleus accumbens septi of the septal lesioned animals primed with EB there was both a reduction in endogenous levels (20–50%) and a decrease in synthesis rates (30–70%) of DA relative to both EB and oil treated sham operated groups and the oil treated septal lesioned group. The EB treated septal lesioned animals showed a significant negative correlation between DA levels in the corpus striatum and the level of lordosis behavior ( r = −.850), supporting the concept of a possible inhibitory role for DA on female sexual receptivity. Glutamic acid decarboxylase (GAD; the rate limiting enzyme in the synthesis of γ-aminobutyric acid (GABA)) activity was measured in the substantia nigra and ventral tegmental region from the same animals. GAD activity was reduced in both areas in the EB primed sham operated animals, while the EB and oil treated septal lesioned groups remained comparable to the oil treated sham operated animals. Because of the proposed existence of a GABA mediated inhibitory neuronal feedback on DA cell bodies in the midbrain, the reduction in DA turnover in the EB primed septal lesioned female rat and thus the increase in behavioral receptivity could be due in part to the failure of the septal lesioned animal to show a compensatory decrease in GAD activity.

The in vitro cellular synthesis of hemoglobin components in various media and its relevance to the concept of stenogenic and eurygenic states of differentiation

The increase above normal in the rate of synthesis of human fetal hemoglobin in incubated cells from adults, as observed previously, is only relative. The addition of serum to the incubation medium tends to reestablish the normal ratio of rates. In the absence of serum the decrease in rates of synthesis affects most strongly the hemoglobin component, whichever it be, that is synthesized more intensively at the cell stage under consideration. This is brought out by the comparison of the effects of different media on fetal and adult cells. The data lead to the definition of the concept of stenogenic and eurygenic states of differentiation.