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Down-regulation of steroidogenic cytochrome P450XVII in cryptorchid rat testes
N Kühn-Velten1, J Rediger, W Staib
1Institut für Physiologische Chemie II, Heinrich-Heine-Universität, Düsseldorf, Germany.
Abstract:
The objective of the present study was to investigate the regulation of a key component of testicular androgen biosynthesis, i.e. the cytochrome P450XVII of the steroid-17 alpha-monooxygenase/C17,20-lyase, after surgical induction of bilateral cryptorchidism in vivo. Seven days after induction of cryptorchidism, P450XVII concentrations are diminished (as compared to sham-operated controls) by 64% in isolated purified Leydig cells but only by 44% in the total Leydig cell compartment of the testis, since the Leydig cell yield from cryptorchid testes is by 53% higher than that from control testes. Using microsomal suspensions prepared from testicular homogenates, P450XVII content per testis equivalent is found to be decreased by 36% seven days after incubation of cryptorchidism, whereas the P450XVII concentration per gram testis is not changed due to testicular involution. Fourteen days after induction of cryptorchidism, the induction of the Leydig cell system appears to superimpose on the down-regulation of P450XVII. The study demonstrates both a strong sensitivity of P450XVII to short-term elevation of testicular temperature and a differentiation between effects of cryptorchidism on total testicular content and specific cellular and subcellular concentration of this steroidogenic protein.
Insights
Surgical induction of cryptorchidism significantly reduces cytochrome P450XVII (steroid-17 alpha-monooxygenase/C17,20-lyase) in Leydig cells. This highlights the sensitivity of androgen biosynthesis to elevated testicular temperature.
Area of Science:
- Reproductive Endocrinology
- Steroidogenesis Biochemistry
Background:
- Testicular androgen biosynthesis is crucial for male reproductive function.
- Cytochrome P450XVII (steroid-17 alpha-monooxygenase/C17,20-lyase) is a key enzyme in androgen production.
- Cryptorchidism, an undescended testis condition, can impair testicular function.
Purpose of the Study:
- To investigate the regulation of cytochrome P450XVII in testicular androgen biosynthesis following induced cryptorchidism.
- To assess the impact of elevated testicular temperature on P450XVII levels in Leydig cells and the overall testis.
Main Methods:
- Surgical induction of bilateral cryptorchidism in an in vivo model.
- Quantification of P450XVII concentrations in isolated Leydig cells and testicular homogenates.
- Comparison of P450XVII levels between cryptorchid and sham-operated control groups at 7 and 14 days post-surgery.
Main Results:
- Seven days after cryptorchidism induction, P450XVII concentration decreased by 64% in purified Leydig cells and 44% in the total Leydig cell compartment.
- P450XVII content per testis equivalent decreased by 36%, while concentration per gram of testis remained unchanged due to testicular involution.
- Fourteen days post-induction, Leydig cell proliferation appeared to offset the down-regulation of P450XVII.
Conclusions:
- Cytochrome P450XVII exhibits high sensitivity to short-term increases in testicular temperature.
- Cryptorchidism differentially affects the total testicular content versus cellular and subcellular concentrations of P450XVII.
- These findings provide insights into the regulation of androgen biosynthesis under conditions of thermal stress.