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cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors
M D Maines1, P M Sluss, M Iscan
1Department of Biophysics, University of Rochester School of Medicine, New York 14642.
Endocrinology
|May 1, 1990
Summary
Cis-platinum chemotherapy significantly reduces testosterone levels by decreasing Leydig cell LH receptors and inhibiting mitochondrial side-chain cleavage activity in rats. Human chorionic gonadotropin (hCG) reverses these effects by increasing testosterone production.
Area of Science:
- Endocrinology
- Toxicology
- Reproductive Biology
Background:
- Cis-platinum is a widely used chemotherapeutic agent with known side effects on reproductive function.
- Previous studies indicated cis-platinum decreases serum testosterone levels, and human chorionic gonadotropin (hCG) can reverse this effect.
Purpose of the Study:
- To elucidate the biochemical mechanisms underlying cis-platinum's impact on testicular testosterone production.
- To investigate the effects of cis-platinum on key enzymes and receptor binding within the testis.
Main Methods:
- Rats were treated with cis-platinum (7 mg/kg, iv) and/or hCG (25 IU/100 g daily).
- Measurements included testicular mitochondrial P-450scc concentration, side-chain cleavage activity, microsomal 17 alpha-hydroxylase activity, cytochrome P-450 concentration, and [125I]hCG binding capacity.
- Pituitary hormone levels (LH, FSH) and response to GnRH challenge were assessed.
Main Results:
- Cis-platinum treatment significantly decreased testicular mitochondrial P-450scc and side-chain cleavage activity by 40%, and microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration.
- Testicular LH receptor binding capacity ([125I]hCG) decreased by 75-80%, while FSH binding remained unchanged.
- hCG administration in cis-platinum-treated rats restored testosterone levels, increased mitochondrial P-450scc and side-chain cleavage activity, and fully occupied remaining LH receptors.
Conclusions:
- Cis-platinum primarily reduces serum testosterone by decreasing the number of Leydig cell LH receptors and inhibiting mitochondrial side-chain cleavage activity.
- The reversal of cis-platinum's effects by hCG or GnRH is attributed to increased LH levels, leading to full occupancy of remaining LH receptors and restoration of steroidogenesis.
- These findings highlight specific testicular targets for cis-platinum's toxicity on testosterone production.