Control of cell growth. II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells

A subclone of rat pituitary tumor cells, designated GH3/C14, was isolated from the parent population of GH3 pituitary cells and was estrogen-dependent for growth in vivo. GH3/C14 cells inoculated into host animals formed tumors in intact females, estrogen-treated ovariectomized females, and estrogen-treated males, but not in untreated intact or castrated males, or untreated ovariectomized females. Exogenous treatment with estrogens supported tumor formation in male animals. Radioimmunoassay of the average serum estradiol concentrations that support tumor growth in intact females, estradiol-treated intact females, and estradiol-treated intact males gave values of 41 +/- 4, 1,130 +/- 150, and 730 +/- 140 pg/ml, respectively. Tumor formation by GH3/C14 cells inoculated into male animals was not supported by either exogenous progesterone or hydrocortisone acetate. Further, these two steroid hormones had no significant effect on the estrogen-promoted growth in males or females. Exogenous testosterone treatment promoted tumor formation in males and ovariectomized females, but dihydrotestosterone was completely ineffective. Radioimmunoassay of the serum from tumor-bearing animals and the medium from the cells in culture showed that the cells produced growth hormone in vivo and in vitro but did not produce measurable amounts of luteinizing hormone or follicle-stimulating hormone. The groth of GH3/C14 cells in culture was examined in medium without added estrogen, and with estradiol added to the level of either the normal intact female rat or the estradiol-treated animals. No direct growth stimulation by estrogens could be detected in culture; the data suggested an indirect growth control mechanism.     

Synthesis and loss of activity of glucose-6-phosphate dehydrogenase in dividing plant cells

1. Using the technique of density-labelling with deuterium oxide, evidence has been obtained for the de novo synthesis of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADPH+ 1-oxidoreductase, EC 1.1.1.49), during the culture of synchronously growing plant cells. 2. The entire increase in enzyme activity during the early cell cycles in this material can be accounted for by the appearance of an enzyme species with increased buoyand density. 3. A method is described for resolving overlapping distribution profiles after density centrifugation, which allows estimation of the amount of each species present at different times, and calculation of the loss of activity of the light species present from the start of culture. 4. Loss of activity of glucose-6-phosphate dehydrogenase in normal growing conditions in the presence of 2,4-dichlorophenoxyacetic acid is very much faster than in conditions which do not lead to cell division: in the absence of 2,4-dichlorophenoxyacetic acid, or in the presence of the inhibitor of RNA synthesis, 6-methylpurine.     

Dissociation of beta-hydroxy-beta-methylglutaryl-CoA reductase activity from the overall rate of cholesterol synthesis in the liver following the intravenous administration of lipid

After the intravenous administration to the intact rat of triglyceride carried in either intestinal lipoproteins or in an artificial fat emulsion, the enzymatic activities of microsomal beta-hydroxy-beta-methylglutaryl-CoA reductase activity in the liver assayed in vitro became markedly elevated. This elevation of enzyme activity was not associated with a corresponding change in the overall rate of cholesterol synthesis in the rat liver slice as measured by the incorporation of either [3H]water or [1-14C]octanoate into nonsaponifiable lipids or into digitonin-precipitable sterols. The degree of dissociation of hydroxymethylglutaryl-CoA reductase activity from the overall rate of cholesterol synthesis correlated closely with the amount of lipid administered to the animal, the level of circulating lipids, and the level of ketone synthesis manifest in the liver cell suggesting that this phenomenon might be the consequence of a detergent effect of elevated cellular levels of fatty acids. In any event, under these experimental circumstances hydroxymethylglutaryl-CoA redutase activity no longer reflects the rate at which the liver cell is synthesizing cholesterol.     

Orientation disruptor (ord): a recombination-defective and disjunction-defective meiotic mutant in Drosophila melanogaster

The effects of a semidominant autosomal meiotic mutant, orientation disruptor (symbol: ord), located at 2-103.5 on the genetic map and in region 59B-D of the salivary map, have been examined genetically and cytologically. The results are as follows. (1) Crossing over in homozygous females is reduced to about seven percent of controls on all chromosomes, with the reduction greatest in distal regions. (2) Crossing over on different chromosomes is independent. (3) Reductional nondisjunction of any given chromosome is increased to about thirty percent of gametes from homozygous females. The probability of such nondisjunction is the same among exchange and nonexchange tetrads with the exception that a very proximal exchange tends to regularize segregation. (4) Equational nondisjunction of each chromosome is increased to about ten percent of gametes in homozygous females; this nondisjunction is independent of exchange. (5) The distributive pairing system is operative in homozygous females. (6) In homozygous males, reductional nondisjunction of each chromosome is increased to about ten percent, and equational nondisjunction to about twenty percent, of all gametes. (7) Cytologically, two distinct meiotic divisions occur in spermatocytes of homozygous males. The first division looks normal although occasional univalents are present at prophase I and a few lagging chromosomes are seen at anaphase I. However, sister chromatids of most chromosomes have precociously separated by metaphase II. Possible functions of the ord(+) gene are considered.     

Intra-arterial sympathetic blockade in the treatment of clinical frostbite

Regional medical sympathectomy achieved by the intra-arterial injection of reserpine appeared to be of benefit in the treatment of five patients with acute or chronic frostbite injuries. Clinical improvement was associated with a significant increase in arteriographically determined regional perfusion.     

Cholesterogenesis: derepression in extrahepatic tissues with 4-aminopyrazolo (3,4-d) pyrimidine

Administration of 4-aminopyrazolo [3,4-d] pyrimidine decreased serum cholesterol levels in the rat to less than 5 milligrams per deciliter. Coincident with this change, there was a 2.1 - to 16.0-fold increase in the rate of sterol synthesis in seven extrahepatic tissues. This suggests that cholesterol carried in serum lipoproteins plays a major role in regulating sterol synthesis in many extrahepatic tissues.     

Sexual education and contentment with the feminine sexual role (author's transl)]

The correlation of sexual education during childhood and the later contentment with the feminine sexual role was quantitively tested for its statistical significance. The data were collected for 386 women with a questionnaire and psychometric testing. Contentment with the feminine sexual role showed correlations to the age of the first sexual education (p smaller than 0.01), to the quality of the sexual education (p smaller than 0.05) and to the experience of the individual sexuality during adolescence (p smaller than 0.05). The earlier and the more positive the sex education the higher was the contentment with the own sexual role. Women who were most content with their presently experienced sexuality were also most content with their social role (p smaller than 0.01). Of importance in the discussion of the results were relationships between the contentment with the sexual role and the age (p smaller than 0.05), neurotic personality traits (p smaller than 0.01), obesity (p smaller than 0.01), psychosomatic complaints (p smaller than 0.05) and the present state of health (p smaller than 0.001). These results are of practical importance for sexual councelling in gynaecology.     

Effects of glutathione-oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils

In human peripheral blood polymorphonuclear leukocytes and lymphocytes, GSH-oxidizing agents promote the movement of surface-bound concanavalin A (Con A) into caps and inhibit the assembly of microtubules (MT) that is normally induced by Con A binding. Con A capping and inhibition of MT assembly occur when GSH levels in cell suspensions are decreased by 30-70%, and return to GSH to control levels is accompanied by the appearance of cytoplasmic MT and by inhibition of the capping response with Con A. Oxidation of GSH markedly stimulates the hexose monophosphate shunt, and regeneration of GSH occurs rapidly. The data indicate that MT cannot be assembled or maintained in the face of decreased GSH levels. Thus, GSH homeostasis becomes critical during physiological events such as phagocytosis which simultaneously induce the assembly of MT and the production of agents like H2O2 that can oxidize GSH.     

Diphosphonate treatment of Paget's disease

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.