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S Sassa

Publications and source records attributed to S Sassa.

At least 199 records · Page 11Linked to original sources
PubMed1981

Uterine estrogen receptor assayed by the controlled pore glass (CPG) method in adult rat after steroid administration.

The interaction of estrogen and androgen was studied at the estrogen receptor level of adult rat uterus by the in vivo experiment. Both the free and total estrogen receptor in the cytosol and nucleus were assayed by the controlled pore glass beads method [2]. Testosterone was given by daily injection for 5 days to the rats treated with estradiol dipropionate (long-acting estradiol) 3 or 5 days before. In the estradiol dipropionate-treated rats the plasma estradiol concentration remained at an extremely high level for 7 days and then decreased to 5-fold of that of proestrus control by the 14th day. There was no significant change in the uterine estrogen receptor of the adult rat with a high estradiol concentration induced by testosterone.

Animals↗
PubMed1980

Adrenalectomy enhances the induction of heme oxygenase and the degradation of cytochrome P-450 in liver.

The induction of hepatic heme oxygenase in response to cobaltous chloride (CoCl2) administration was examined in normal, sham-operated, and adrenalectomized rats. The basal level of heme oxygenase was elevated about 2-fold in adrenalectomized rats as compared to normal controls or sham-operated animals. The extent of heme oxygenase induction by CoCl2 was also increased about 2-fold above normal in adrenalectomized animals and was accompanied by an enhanced breakdown of cytochrome P-450. The initial decline (approximately 2 h) and the late rebound increase (approximately 16 h) of delta-aminolevulinate synthase activity caused by the metal administration were, however, similar for all three groups of animals. Hydrocortisone is known to restore the impaired inducibility of delta-aminolevulinate synthase by allylisopropylacetamide in adrenalectomized rats. In this study, treatment with hydrocortisone prevented the exaggerated metal induction of heme oxygenase but did not affect the associated initial decline or the late rebound of delta-aminolevulinate synthase. These data indicate that hydrocortisone and adrenalectomy can significantly influence the extent of the induction of heme oxygenase produced by CoCl2, but that both the initial decline and the rebound induction of delta-aminolevulinate synthase associated with this metal treatment are apparently independent of these endocrine controls.

5-Aminolevulinate Synthetase↗
PubMed1979

Steroid induction of delta-aminolevulinic acid synthase and porphyrins in liver. Structure-activity studies and the permissive effects of hormones on the induction process.

Quantitative aspects and structure-activity relationships of the inducing effects of natural steroids on delta-aminolevulinic acid (ALA) synthase and porphyrins have been investigated in monolayer cultures of chick embryo liver cells maintained in a serum-free medium as well as in the chick embryo liver in ovo. Many 5 alpha and 5 beta metabolites of neutral C-19 and C-21 hormones and hormone precursors stimulated porphyrin formation and ALA-synthase induction in the cultured liver cells as we have previously described. In these inducing actions a number of 5 beta epimers (A:B cis) were found to be more potent than their corresponding 5 alpha epimers (A:B trans). The structure-activity relationship between 5 beta and 5 alpha steroid epimers with respect to ALA-synthase induction in culture was also found to prevail with respect to induction of this enzyme in chick embryo liver in ovo. Hemin in concentrations of 2 x 10(-7) M inhibited steroid induction of porphyrin formation, and CaMgEDTA enhanced the responsiveness of the cultured liver cells to steroids by approximately 10 times. The addition of insulin, or insulin plus hydrocortisone or insulin plus hydrocortisone plus triiodothyronine, was important for the maintenance of protein synthesis and essential for maximal expression of the ability of steroids to induce porphyrins and ALA-synthase in the "permissive" effect which insulin, hydrocortisone, and triiodothyronine exert on allylisopropylacetamide induction of porphyrins and ALA-synthase also extends to the induction process which is elicited by natural steroids. These findings also strongly suggest that the regulation of hepatic porphyrin-heme biosynthesis by endogenous as well as exogenous chemicals is significantly influenced by the internal hormonal milieu.

5-Aminolevulinate Synthetase↗
PubMed1979

The influence of steroid hormone metabolites on the in vitro development of erythroid colonies derived from human bone marrow.

Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin. Among a number of pairs of C5 epimeric steroids tested, most 5beta (A:B cis) steroids stimulated the growth of both early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E), whereas only a few 5alpha-(A:B trans) steroids stimulated the growth of CFU-E. No 5alpha-compounds of six pairs of steroids studied were found to stimulate BFU-E formation. This structure-activity relationship conforms with that previously observed in studies of steroid induction of ALA-synthase in avian embryo liver cells and hemoglobin synthesis in the cultured avian blastoderm. When human bone marrow cells were preincubated with the steroids for 2 d, followed by incubation with erythropoietin, only the 5 beta-compounds stimulated the growth of BFU-E. Similarly, when addition of steroids was delayed in relation to erythropoietin in the culture, only the 5 beta-derivative of a pair of C5 epimeric compounds displayed an enhancing effect on the growth of BFU-E. This effect required that the steroid addition be made no later than 48 h after initiation of the culture. These data demonstrate that certain natural steroid metabolites significantly stimulate erythropoiesis in normal human bone marrow cells in culture. They also indicate that 5 beta-compounds are more stimulatory than their 5 alpha-epimers, and they suggest that these 5 beta-steroids act preferentially on very primitive erythroid progenitor cells, probably on BFU-E.

Androstanes↗
PubMed1979

[The behavior of 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats during pregnancy and lactation and hormone levels in the pituitary and plasma (author's transl)].

In order to keep a long-term lactation in primiparous SD strain rats with DMBA-induced mammary tumors, 5 pups aged 5 to 10 days were exchanged every 10 days. FSH, LH and prolactin (PRL) in pituitary tissues and FSH, LH, PRL, estradiol (E2) and progesterone (PRG) in plasma were determined during pregnancy (1,2 and 3-week), at paturition (0 to 12 hours after parturition) and during lactation (1,2,3,4,5 and 6-week). Experimental rats were divided into 6 groups according to the lactating period (non-lactating 3,6,8,12 and 17-week). Blood samples were collected by cardiac puncture 1 hour after an intraperitoneal injection of urethane (150 mg/100 g body weight), and the pituitary gland was removed simultaneously. During pregnancy, plasma PRL was low in the first and second week. PRL, E2 and PRG were high in the third week, during which DMBA-induced mammary tumors began to proliferate. PRG in plasma in the third week was lower than that of the second week. After paturition, the tumors regressed and did not develop for three weeks of lactation, during which plasma PRL was high whereas E2 and PRG were low. The tumors began to proliferate again from the fifth week of lactation, during which E2 was high and the estrous cycle reappeared. The behavior of DMBA-induced mammary tumors in rats during pregnancy and lactation seems to be closely related to plasma estrogen levels.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Uroporphyrinogen I synthase induction in normal human bone marrow cultures: an early and quantitative response of erythroid differentiation.

Uroporphyrinogen I (URO) synthase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] activity increased when cultures of normal human bone marrow cells were incubated with erythropoietin. The increase of URO synthase activity was a linear function of erythropoietin concentration in the culture medium and was proportional to the extent of heme synthesis as determined by 55Fe incorporation into heme. The onset of the increase in URO synthase activity, which occurred on day 4 of incubation with erythropoietin, preceded by 3 days the appearance of hemoglobin in colonies derived from erythroid progenitor cells. These results indicate that induction of URO synthase in normal human bone marrow cells incubated with erythropoietin is an early event and that URO synthase activity is a useful quantitative index of erythroid differentiation.

Adult↗
PubMed1979

Tumor promoter-mediated inhibition of cell differentiation: suppression of the expression of erythroid functions in murine erythroleukemia cells.

Previous studies demonstrated that 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a tumor promoter, is a potent inhibitor of inducer-mediated differentiation of murine erythroleukemia cells. Inhibition of cell differentiation was associated with inhibition of cell growth. The present studies, employing a cell line adapted for growth in TPA, demonstrate that inhibition of differentiation is not dependent upon inhibition of cell growth or a change in the cell division cycle; neither is inhibition of differentiation accompanied by detectable effect on cell uptake of [3H]hexamethylene bisacetamide, the inducer used in these studies. TPA causes an inhibition of expression of all hexamethylene bisacetamide-inducible erythroid characteristics measured, including commitment to terminal cell division, accumulation of globin mRNA, and synthesis of globins, spectrin, heme synthetic enzymes (delta-aminolevulinic acid dehydratase and uroporphyrinogen-I synthase) and heme. A hypothetical model for the inhibitory action of tumor promoters on terminal cell differentiation is discussed.

Cell Differentiation↗
PubMed1979

Studies in porphyria IX: Detection of the gene defect of erythropoietic protoporphyria in mitogen-stimulated human lymphocytes.

We have demonstrated in this study that mitogen-stimulated lymphocytes from EPP subjects accumulate substantially greater amounts of protoporphyrin IX than do normal lymphocytes when incubated with ALA. Protoporphyrin IX formation by normal lymphocytes is stimulated by CaMgEDTA, an inhibitor of ferrochelatase, and is decreased by ferrous iron which facilitates the utilization of protoporphyrin IX for heme synthesis. In contrast, protoporphyrin IX formation by EPP lymphocytes is less stimulated by CaMgEDTA than is the case with normal lymphocytes and is only slightly affected by iron. Clinically manifested EPP subjects and completely latent gene carriers of EPP can be identified using this lymphocyte culture technique. The data from this study provide clear evidence of a functional deficiency of ferrochelatase activity in human EPP lymphocytes. EPP thus represents the third of the three dominant porphyric disorders of man, including acute intermittent porphyria and hereditary coproporphyria, which can now be diagnosed using lymphocytes.

Adolescent↗
PubMed1978

Hemin control of heme biosynthesis in mouse Friend virus-transformed erythroleukemia cells in culture.

Hemin treatment of mouse Friend virus-transformed cells in cultured caused a dose-dependent increase in hemoglobin synthesis. By the addition of radioactively labeled hemin and by the analysis of the radioactive heme in hemoglobin, only 60 to 70% of heme in the newly synthesized hemoglobin was accounted for by the exogenously added hemin. In keeping with this finding, hemin treatment increased the activity of two enzymes in the heme biosynthetic activity, i.e. delta-aminolevulinate (ALA) dehydratase and uroporphyrinogen-I (URO) synthase in these cells. Incorporation of [2(-14C)]glycine, [14C]ALA, and 59Fe into heme was also significantly increased in the cells treated with hemin, suggesting that essentially all enzyme activities in the heme biosynethetic pathway were increased after hemin treatment. These results indicate that heme in the newly synthesized hemoglobin in hemin-treated Friend cells derives both from hemin added to the culture and from heme synthesized intracellularly. In addition, these results suggest that the stimulation of heme biosynthesis by hemin in Friend virus-transformed cells is in contrast to the hemin repression of heme biosynthesis in liver cells.

Animals↗
PubMed1978

Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids.

Erythrodifferentiation and hemoglobin synthesis in dimethyl sulfoxide-stimulated Friend erythroleukemia cells were inhibited by hydrocortisone (HC) and four other steroids: dexamethasone, deoxycorticosterone, corticosterone, and aldosterone. The effect was specific, because no significant cytotoxicity occurred with any of these compounds at the concentrations that were inhibitory. The mechanism of action of HC was studied in detail. In the absence of dimethyl sulfoxide, it had no effect on hemoglobin levels; but, in the presence of this inducer, the synthesis of heme and globin were each inhibited by approximately 90%. There was no alteration in the synthesis of any major protein other than globin, as determined by gel electrophoresis of cell lysates. The activities of two enzymes in the heme biosynthetic pathway, delta-aminolevulinate dehydratase and uroporphyrinogen-I synthase, were inhibited by 80% and 70%, respectively. Globin mRNA induction was reduced by approximately 90%. This demonstrated that the HC inhibition of globin synthesis occurred at a pretranslational step. The dimethyl sulfoxide-induced single-stranded breaks in DNA, which have been suggested to play a role in Friend leukemia cell differentiation, were reduced in number but not eliminated. HC reduced the dimethyl sulfoxide-stimulation of virus release into the medium by approximately 50%. HC treatment in the absence of dimethyl sulfoxide doubled the production of virus.

Aldosterone↗
PubMed1978

Studies on porphyrin-heme biosynthesis in organotypic cultures of chick dorsal root ganglion. I. Observations on neuronal and non-neuronal elements.

Living, mature organotypic cultures of chick dorsal root ganglion maintained in culture for 3 weeks were incubated in medium containing various levels of a precursor of porphyrin and heme formation, delta-aminolevulinic acid (ALA), (0.5 mM to 10 mM) or a combination of ALA (10 MM) and a metal chelator, CaMg-EDTA (5 mM) for up to 48 hours. Although no morphologic changes occurred in the cultures incubated with these compounds as observed by bright-field or dark-field microscopy, fluorescence microscopic study at 12, 24, and 48 hours demonstrated an intense red fluorescence with in the non-neuronal cells of the cultures (Schwann cells, fibroblasts, and macrophages) but not in the nerve cells. Spectrofluorometric analysis of perchloric acid-methanol extracts of the cultures revealed an emission spectrum characteristic of porphyrins. Autoradiographic studies, using 14C-labelled ALA, indicated that ALA was taken up by all cells (nerve cells as well as non-neuronal cells) in the cultures. The cultures incubated with ALA plus the metal chelator CaMg-EDTA showed the same distribution of porphyrin fluorescence, but a 2-fold increase in the amount of porphyrins was generated, when compared to cultures incubated with ALA alone. This observation suggests that a considerable fraction of porphyrins may be utilized to form heme in these cells since CaMa-EDTA blocks ferrochelatase activity, the terminal enzyme in the heme biosynthetic pathway. This is the first demonstration of active porphyrin-heme biosynthesis from ALA in cultured nervous system cells. Our results indicate that this biosynthetic pathway remains active in 3-week old cultures of chick dorsal root ganglion, and further, that the pathway appears to be predominantly present in the non-neuronal cellular elements of the ganglion rather than in nerve cells.

Aminolevulinic Acid↗
PubMed1978

Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.

A 50% reduction in the activity of uroporphyrinogen-I (URO) synthase in liver, erythrocytes, and cultured skin fibroblasts characterizes all patients with clinically active acute intermittent porphyria (AIP). The same enzyme defect has also been demonstrated in the erythrocytes and skin fibroblasts of completely latent gene carriers of this disorder and presumably exists in the liver as well. In this study, we examined whether or not the formation of URO-synthase is impaired in AIP cells using lymphocytes treated with mitogens or infected with Epstein-Barr virus. Both mitogens (phytohemagglutinin and pokeweed mitogen) and Epstein-Barr virus induced the synthesis of URO-synthase in lymphocytes, but the induction of URO-synthase in AIP lymphocytes was only 50% as compared with that in normal lymphocytes. The impaired induction of URO-synthase in AIP lymphocytes reflects a specific gene defect because AIP lymphocytes showed normal [(3)H] thymidine uptake into DNA, [(3)H] uridine uptake into RNA, and normal delta-aminolevulinic acid (ALA) synthase, ALA-dehydratase, catalase activities, and heme content. Utilizing the same methodology, the ferrochelatase deficiency of hereditary erythropoietic protoporphyria could also be identified. The K(m) of the induced URO-synthase in AIP cells was identical to that of the enzyme in normal cells. The induced URO-synthase of mitogen-treated AIP lymphocytes was not accompanied by a concurrent enhanced level of ALA-synthase. Moreover, the URO-synthase deficiency in lymphocytes from actively ill AIP patients was not different from the level of enzyme activity when they were in clinical remission, or when compared with the enzyme activity of cells from completely latent AIP gene carriers. The results of this study indicate that the URO-synthase deficiency in AIP may be the result of a gene mutation regulating the rate of synthesis of a normal enzyme rather than a mutation causing a structural abnormality of this enzyme protein.

Acute Disease↗