Hormone control of heme synthesis in cultures of human fetal liver cells

Congote, L.F.; Stern, Martin; Solomon, Samuel

doi:10.1021/bi00718a002

Cited by 15 publications

(25 citation statements)

References 34 publications

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“…The maximum stimulation was observed in cells taken from fetuses of 10-11 weeks of gestation (7). After the addition of testosterone the incorporation of uridine into total RNA remained unchanged in cells from fetuses of [10][11][12][13][14][15] without testosterone or erythropoietin present in the culture medium.…”

Section: Resultsmentioning

confidence: 91%

“…Fig. 2 shows the sedimentation characteristics of the RNA synthesized in freshly prepared fetal liver cultures, which consist mainly of erythroid cells (7), and of RNA synthesized by cells of other tissues under identical conditions. The RNA synthesized in kidney and lung cells after a 1-hr pulse with radioactive uridine is heterogeneous and consists mainly of high-molecular-weight species.…”

Section: Resultsmentioning

confidence: 99%

“…The methods used in preparing these solutions have been described in detail (7). The methods for the preparation of primary cultures of kidney, lung, and liver cells have been described (7,12). All experiments with primary liver erythroid cells were done 1 day after plating.…”

Section: Introductionmentioning

confidence: 99%

“…We have found that primary cultures of erythroid cells from human fetal liver exhibited an enhanced synthesis of heme after addition of erythropoietin or testosterone and that the heme fraction associated with hemoglobin showed the highest stimulation (7).…”

mentioning

confidence: 96%

“…One is the high degree of specificity of the action of 5,B-reduced steroids in human bone marrow cells, where both heme and globin synthesis are stimulated (11 centrations were 50 nM testosterone and 0.5 U/ml of erythropoietin. The methods used in preparing these solutions have been described in detail (7). The methods for the preparation of primary cultures of kidney, lung, and liver cells have been described (7,12).…”

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confidence: 99%

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Testosterone stimulation of a rapidly labeled, low-molecular-weight RNA fraction in human hepatic erythroid cells in culture.

Congote¹,

Solomon²

1975

Proc. Natl. Acad. Sci. U.S.A.

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The addition of erythropoietin to cell cultures of erythroid cells of human fetal liver resulted in an increased incorporation of thymidine, adenine, and uridine into trichloroacetic acid-insoluble cell fractions and in an increased uptake of adenine and uridine into the cell. Although the effects of testosterone and erythropoietin on heme synthesis in these cells are known to be very similar, there was no effect of testosterone on the total incorporation of radioactive precursors into DNA or RNA. The RNA synthesized after short pulses of radioactive uridine, when analyzed on sucrose gradients containing 1% sodium dodecyl sulfate, consisted of a homogeneous peak sedimenting at 10 i 2 S, which is quite different from the heterogeneous, high-molecular-weight RNA synthesized under identical conditions in primary cultures of human fetal lung, kidney, or liver parenchymal cells. Addition of testosterone to liver erythroid cells in cultures for 5 hr followed by a 1-hr uridine pulse resulted in a 3-fold increase of RNA species with an average sedimentation coefficient of 14 A4 3 S. The similarity with the sedimentation coefficient of the globin mRNA described in other systems and the high degree of specialization of the erythroid cells suggest that this RNA may be a stable intermediate involved in the synthesis of hemoglobin.One of the earliest actions of erythropoietin on its target cells is the stimulation of RNA synthesis (1-6). We have found that primary cultures of erythroid cells from human fetal liver exhibited an enhanced synthesis of heme after addition of erythropoietin or testosterone and that the heme fraction associated with hemoglobin showed the highest stimulation (7).At the present time it cannot be said with certainty if testosterone itself is active in hematopoietic cells or whether it exerts its effects via a metabolite(s) with the 5,8-configuration. Several observations support a direct role of testosterone. Erythropoietic mouse spleen and rat bone marrow cells contain testosterone receptors, and there is no metabolism of the hormone in mouse spleen (8,9). The effects of testosterone on colony formation in hematopoietic cells of mice are seen within a few minutes after hormone administration (10) when extensive metabolism of the hormone is not to be expected. In this system testosterone and 5(3-metabolites are equally active in colony formation, whereas in human fetal erythroid cells testosterone seems to be the most active of a large number of steroids tested to date (ref. 7, and our own unpublished results). There are two pieces of evidence that suggest a role of metabolites with the 5(3-configuration. One is the high degree of specificity of the action of 5,B-reduced steroids in human bone marrow cells, where both heme and globin synthesis are stimulated (11). Another supporting piece of evidence is the rapid metabolism of testosterone to androstenedione and 523 etiocholanolone in human fetal liver cells (7 centrations were 50 nM testosterone and 0.5 U/ml of erythropoietin. The methods us...

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 3 more Smart Citations

Testosterone stimulation of a rapidly labeled, low-molecular-weight RNA fraction in human hepatic erythroid cells in culture.

Congote¹,

Solomon²

1975

Proc. Natl. Acad. Sci. U.S.A.

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The Mechanism of Action of Erythropoietin: Erythroid Cell Response

Spivak¹

1992

Biochemical Pharmacology of Blood and Bloodforming Organs

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The effect of testosterone administration on lead induced zincprotoporphyrin in blood concentration in castrated male rabbits

Wibowo

Zielhuis

1981

Arch Toxicol

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The influence of testosterone propionate on the concentration of zincprotoporphyrin in blood (ZPP) of castrated lead treated rabbits was investigated. The experimental design allowed comparison of the relative ZPP increase (RZI) in testosterone treated and non testosterone treated rabbits. Testosterone was administered by subcutaneous injection of 3 mg/kg body weight/day for 7 consecutive days directly prior to the lead exposure, which was performed by subcutaneous injection of 0.50 mg lead acetate/kg body weight, three times a week for 7 weeks. No effect was found on the hemoglobin concentration (Hb) and hematocrit (Ht) and on the increase of body weight during the experiment. But the increase of RZI in the non testosterone treated rabbits was significantly steeper and earlier than in the testosterone treated group. The possible consequences of the findings had been further commented on.

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Hormone control of heme synthesis in cultures of human fetal liver cells

Cited by 15 publications

References 34 publications

Testosterone stimulation of a rapidly labeled, low-molecular-weight RNA fraction in human hepatic erythroid cells in culture.

Testosterone stimulation of a rapidly labeled, low-molecular-weight RNA fraction in human hepatic erythroid cells in culture.

The Mechanism of Action of Erythropoietin: Erythroid Cell Response

The effect of testosterone administration on lead induced zincprotoporphyrin in blood concentration in castrated male rabbits

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