The authors describe an intoxication by Atractylis gummifera in a 7-year old boy who drunk an extract made from the plant's root as traditional medicine. He was admitted to the Hospital 2 days after ingestion, in coma stage II, with epigastric pain, vomiting and general anxiety. Laboratory findings showed severe hepatocellular damage and acute renal failure. In spite of all treatment and therapeutic efforts, the boy died 8 days after admission. A postmortem histopathological study of the liver confirmed the panlobular hepatic necrosis and allowed the differential diagnosis of the intoxication from Reye syndrome.

Acute Kidney Injury↗

PubMed1987

Regulation of mitochondrial and microsomal cytochrome P-450 enzymes in Leydig cells.

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17-Hydroxysteroid Dehydrogenases↗

PubMed1987

Functional and physical characteristics of rat Leydig cell populations isolated by metrizamide and Percoll gradient centrifugation.

The physical and functional properties of Leydig cell populations obtained by centrifugation of testicular cells in two different density gradient media, Percoll and Metrizamide, were compared. Percoll-gradient centrifugation yielded two Leydig cell bands (Peak I and Peak II) that were comparable, as to their density and testosterone-producing capacity, to the respective Leydig cell bands, Population I and Population II, isolated in a Metrizamide gradient. The denser Leydig cell band (II) had a greater capacity for testosterone production than the less dense band (I), regardless of the type of gradient used for its isolation. Metrizamide gradient centrifugation separated the majority of germ cells from the "light" (Population I) Leydig cells, whereas in the Percoll gradient, germ cells comigrated with Peak I Leydig cells. Leydig cell separation by Percoll gradients was highly dependent on the presence of Ca2+ and Mg2+ in the medium, while these cations had no effect on the separation of Leydig cells by Metrizamide. In conclusion, Metrizamide gradient centrifugation yielded two Leydig cell populations of similar functional and physical properties to the respective populations isolated in Percoll gradients.

Animals↗

PubMed1987

Steroid synthesis-dependent, oxygen-mediated damage of mitochondrial and microsomal cytochrome P-450 enzymes in rat Leydig cell cultures.

Treatment of primary cultures of rat Leydig cells with 1 mM 8-bromo-cAMP for 2 days at ambient oxygen tension (19%) caused a 59% decrease in mitochondrial cholesterol side-chain cleavage (P-450scc) activity. This decrease was completely prevented when the oxygen tension was reduced to 1% O2 or when steroid synthesis was inhibited by aminoglutethimide. When the endogenous concentration of pregnenolone was increased by inhibiting its further metabolism, P-450scc activity was reduced by 80% in unstimulated cultures and was completely eliminated in cAMP-treated cultures. These losses were prevented when cells were maintained at 1% O2. The amount of immunoreactive P-450scc was also decreased by treatments that reduced P-450scc activity. Stimulation with cAMP also lowered microsomal C17-20 lyase activity by an oxygen-mediated, steroid synthesis-dependent mechanism. Treatment of cultures with testosterone caused a similar oxygen tension-sensitive decrease in C17-20 lyase activity. These results suggest that the enhanced loss of mitochondrial and microsomal cytochrome P-450 activities in cAMP-treated cultures is caused by the increased production of pregnenolone and testosterone, respectively, which generate reactive damaging species derived from reduced dioxygen. The increased catalytic turnover of these P-450 enzymes may also contribute to their damage. Although P-450 activities were preserved at 1% O2, the ability of cAMP-treated cells to synthesize testosterone in response to subsequent cAMP stimulation was still reduced. If, however, 25-hydroxycholesterol was supplied to these cells the decrease in testosterone-producing capacity was prevented, which demonstrates that the reduced steroidogenic capacity of cAMP-treated Leydig cells is caused, primarily, by the reduced availability of endogenous cholesterol.

Aldehyde-Lyases↗

PubMed1985

Differences in the control of sterol metabolism between mouse and rat Leydig cells.

The metabolism of hydroxysterols, which bypass the cAMP-dependent, cycloheximide-inhibitable transport to cytochrome P-450 side-chain cleavage enzyme complex (P-450scc) required by cholesterol, and whose metabolism exceeds that of cholesterol in luteal cells, has been investigated in primary cultures of Leydig cells purified from the mouse and the rat. An unexpected finding was that metabolism of 25-hydroxycholesterol by mouse Leydig cells was far lower than cAMP-stimulated cholesterol metabolism. The metabolism of 20 alpha-hydroxycholesterol and 22R-hydroxycholesterol was equivalent to and greater than, respectively, maximal cholesterol metabolism by mouse Leydig cells. As expected, metabolism of 25-hydroxycholesterol by rat Leydig cells was much greater than cholesterol metabolism, as was metabolism of 20 alpha-hydroxycholesterol and 22R-hydroxycholesterol. Hydroxysterol metabolism was not increased by cAMP. Cycloheximide abolished the cAMP-stimulated increase in testosterone production by Leydig cells of both species but had no effect on metabolism of any of the hydroxysterols by Leydig cells of either species. In addition, it was shown that the relatively low rate of 25-hydroxycholesterol supported testosterone production in mouse Leydig cells was not due to inhibition of the conversion of pregnenolone to testosterone. It is concluded that a species-specific difference in the control of mitochondrial sterol metabolism exists between the rat and the mouse. The data suggest that either the P-450scc differs between mice and rats or that an effector of P-450scc, which greatly facilitates the binding and metabolism of cholesterol, is of particular importance in the control of sterol metabolism in the mouse Leydig cell.

Animals↗

PubMed1985

25-Hydroxycholesterol-supported and 8-bromo-adenosine 3',5'-monophosphate-stimulated testosterone production by primary cultures of two populations of rat Leydig cells.

Previous studies from this laboratory have demonstrated the presence of two populations of rat Leydig cells (I and II), which differ in their capacity for hCG- or cAMP-stimulated testosterone production. In the present study, we examined the metabolism of 25-hydroxycholesterol in primary cultures of both populations of Leydig cells. 25-Hydroxycholesterol bypasses the cAMP-dependent transport mechanism to the mitochondrial cytochrome P-450 side-chain cleavage enzyme (P-450scc) required by cholesterol and thus provides an index of the relative activity of P-450scc. Incubation of Leydig cells with increasing concentrations of 25-hydroxycholesterol resulted in a concentration-dependent increase in the amount of testosterone produced, with maximal amounts in both populations being reached at 25-hydroxycholesterol concentrations of 5 microM or greater. Population II produced more than twice as much testosterone as population I Leydig cells, whether incubated with 25-hydroxycholesterol or with 8-bromo-cAMP. Each population of Leydig cells produced 2.5-fold greater amounts of testosterone when incubated with 25-hydroxycholesterol than when incubated with 8-bromo-cAMP. In both populations of Leydig cells, cAMP-stimulated testosterone production was not different in cells cultured for 24 h from that in freshly isolated Leydig cells. These data suggest that cholesterol transport to P-450scc limits maximal testosterone production, and that the difference in hCG- or cAMP-stimulated testosterone production between the two populations of Leydig cells is primarily due to differences in P-450scc activity between the two populations and is not a result of population I consisting mostly of damaged Leydig cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1979