Tissue culture of bone marrow. V. Effect of 5Beta(H) steroids and cyclic AMP on heme synthesis

Abstract

In mice 5beta(H) steroids have been shown tostimulate heme synthesis in vivo. The current studies were undertaken to evaluate the effect of these steroids on heme synthesis by use of the "well" method of marrow culture. The 5beta(H) steroid metabolites 3alpha-hydroxy-5beta-pregnane-11, 20-dione, 3beta-hydroxy-5beta-pregnan-20-one, 3 alpha,17alpha-dihydroxy-5beta-androstan-3-one stimulated Fe uptake by human marrow explants cultured in wells. The dibutyrl analog of adenosine 3',5'-monophosphate (db cAMP) also stimulated Fe uptake. The effect of the latter compound was enhanced by theophylline. There was no additive nor synergistic effect between db cAMP and the 5beta(H) steroid metabolites. There was no inhibition of the steroid metabolite effect by either antierythropoietin serum or cyproterone. Uptake of fe was also enhanced by the cations Ca++ and Co++.

Evolution of Serum Erythropoietin after Androgen Administration to Hemodialysis Patients: A Prospective Study

“…They do not increase the red-cell survival [3], Preliminary studies showed that androgens produced a rise in the serum erythropoietin activity that was attribut ed to the stimulation of endogenous erythropoietin secre tion [1,4], but these data were not confirmed later [5], perhaps because of the low sensitivity of the assay used. Other studies discovered that androgens produced a di rect stimulation of marrow heme synthesis [6], augmenta tion of growth by differentiated stem cells [7] and enhanc ing the sensitivity of erythroid progenitors to circulating erythropoietin [5, 8. 9].…”

Bone Marrow Cyclic Nucleotides (cAMPcGMP) in Phenylhydrazine-Induced Anemia

“…Stimulation of heme and hemoglobin synthesis by cAMP and dbcAMP in cultures of bone marrow ob tained from various animals was confirmed by inves tigations carried out by many authors [2,14,15,21]. This effect was intensified in the cultures enriched with theophylline [14], Another view on the role of cyclic nucleotides has been presented by Rodgers et al [26].…”

“…This effect was intensified in the cultures enriched with theophylline [14], Another view on the role of cyclic nucleotides has been presented by Rodgers et al [26]. This assumes that cGMP is an important nu cleotide mediating the response of erythroid cells to erythropoietin and an active signal in response to erythropoietic stimulating factor.…”

“…A synergistic action of erythropoietin and cAMP has also been noted. The administration of cAMP and its dibutyryl derivative resulted in an in crease in 59Fe incorporation into erythrocytes in mice in vivo [25], as well as in human bone marrow cultures [14].…”

Early Increase of Cyclic Adenosine Monophosphate Level Induced by Erythropoietin on Rabbit Bone Marrow Cell Suspensions

“…Various attempts at verifying the possi bility that Ep action could be mediated through variations of the intracellular level of cyclic nucleotides (a well-established no tion for the action of several proteinaceous hormones [17]) have been reported [5,10,12,18,21]. Increases of cyclic guanosine monophosphate (cGMP) in rabbit bone marrow cultures, in spleen cell suspensions of mice and in fetal liver cells of rats have been found 24 h after treatment with Ep [11].…”