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Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse
L Murphy1, I A Jeffcoate, P J O'Shaughnessy
1Department of Veterinary Physiology, University of Glasgow Veterinary School, Scotland.
Endocrinology
|October 1, 1994
Summary
Leydig cells require androgen receptor activity for normal development around day 25. Without androgen receptors, fetal Leydig cell steroidogenesis is enhanced, but adult function is impaired, impacting testicular descent and enzyme activity.
Area of Science:
- Reproductive Biology
- Endocrinology
- Developmental Biology
Background:
- Leydig cells are the primary source of male androgens and are also targets for androgen action.
- The role of androgens in Leydig cell development is crucial for male reproductive function.
- The testicular feminized (Tfm/Y) mouse model lacks androgen receptors, providing a tool to study androgen's role.
Purpose of the Study:
- To investigate the role of androgen action in regulating Leydig cell function during development.
- To determine the impact of androgen receptor absence on Leydig cell steroidogenesis and function.
- To examine the relationship between Leydig cell development, testicular descent, and androgen receptor activity.
Main Methods:
- Utilized testicular feminized (Tfm/Y) mice lacking androgen receptors and control (+/Y) mice.
- Surgically prevented testicular descent in control animals to isolate developmental effects.
- Measured enzyme activities (3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17-ketosteroid reductase) and serum LH levels at various developmental stages (5-40 days).
Main Results:
- Fetal Leydig cell steroidogenesis was enhanced in Tfm mice (lacking androgen receptors).
- Adult Leydig cells in Tfm mice showed impaired development of 17 alpha-hydroxylase and 17-ketosteroid reductase activity.
- Lack of testicular descent at 25 days reduced the pubertal rise in 17 alpha-hydroxylase activity, indicating a role for descent in Leydig cell maturation.
Conclusions:
- Androgen receptor-mediated activity around day 25 is essential for normal adult Leydig cell functional development.
- The absence of androgen receptors enhances fetal Leydig cell steroidogenesis but impairs adult Leydig cell function.
- Testicular descent is linked to the pubertal increase in specific Leydig cell enzyme activities, highlighting its importance in reproductive maturation.