Characterization of heme oxygenase activity in Leydig and Sertoli cells of the rat testes. Differential distribution of activity and response to cadmium.
Leydig and Sertoli cells of the rat testes differ with respect to the activities of the enzymes of the heme and hemoprotein degradative pathway and in their responses to Cd2+ treatment. The microsomal heme oxygenase activity in the Leydig cell preparations was nearly 9- to 10-fold greater than in Sertoli cell preparations, but the characteristics of the enzyme appeared to be similar in both cell populations, as judged by the cofactor requirements and the inhibitory action of heme ligands. Differences between the two cell preparations also were detected in the activity of NADPH-cytochrome c (P-450) reductase and in the contents of cytochrome P-450 and heme, with Leydig cells possessing the higher values. The activities of the cytosolic biliverdin reductase were comparable in both cell preparations. The significantly higher levels of porphyrins and the activities of delta- aminoleuvinate synthetase and uroporphyrinogen-I synthetase suggest that Leydig cells constitute the primary site of heme and hemoprotein biosynthetic activities. The mode of regulation of heme oxygenase activity in the testes and in the liver was compared. The responses of heme oxygenase to Cd2+ treatment (20 mumoles/kg, 24 hr) in the two testicular cell populations were dissimilar and both differed from that of the liver. In Leydig cells, heme oxygenase activity was decreased dramatically, whereas in the liver the activity was greatly increased. Heme oxygenase activity in Sertoli cells was refractory to Cd2+. The Cd2+-mediated decrease in heme oxygenase activity in Leydig cells did not reflect a direct inhibitory action of Cd2+ on the enzyme or a decreased total content of the microsomal protein. The dissimilarity between the mode of regulation of heme metabolic activities in the testes, when determined in Leydig cells, and that in the liver involved the inability of bromobenzene to evoke an increase in heme oxygenase activity and the age-related changes in the activities of heme oxygenase and delta- aminoleuvinate synthetase. In contrast to heme oxygenase activity, the heme concentration in Sertoli cells was remarkably sensitive to Cd2+ treatment, where a 7-fold increase in heme concentration was observed. The same treatment caused only a 2-fold increase in heme concentration in Leydig cells. In the latter cells, however, the increase in heme concentration was accompanied by a marked reduction in cytochrome P-450 levels. The cytochrome could not be measured in Sertoli cell preparations.(ABSTRACT TRUNCATED AT 400 WORDS)
D000367:Age Factors; D000818:Animals; D001969:Bromobenzenes / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D006418:Heme / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis*; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis*; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D010088:Oxidoreductases / Q000032:analysis; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010634:Phenobarbital / Q000494:pharmacology; D000623:Porphobilinogen Synthase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000201:enzymology*
D001969:Bromobenzenes; D002104:Cadmium; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D006419:Heme Oxygenase (Decyclizing); D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D009251:NADPH-Ferrihemoprotein Reductase; D000623:Porphobilinogen Synthase; D010634:Phenobarbital