The Effects of Testosterone on Leydig Cell Development in Male YHR+ Mice

摘要

Leydig cells (LC) are specialized cells in the testis that develop during puberty and are responsible for producing testosterone. Luteinizing Hormone (LH) and testosterone are important for LC development. Binding of LH to its receptor (LHR) initiates the production of testosterone. Constitutively active mutations in LHR have been identified in humans resulting in puberty in males as young as 3 or 4 years of age. A transgenic mouse (YHR+), was generated which mimics the constitutively active LHR by fusing the hormone, human chorionic gonadotropin, to LHR to continually activate the receptor. Testosterone levels in YHR+ mice are high at neonatal ages. Previous studies in the lab have shown that YHR+ mice have decreased LC numbers compared to wild type (WT) mice. It was hypothesized that high levels of testosterone at neonatal ages was responsible for the decrease in LC numbers and was causing a decrease in the proliferation of LCs. To test this hypothesis, the action of testosterone was blocked with the androgen antagonist, flutamide, and the total number of LCs as well as the number of proliferating LCs were determined. There was no significant increase in LC number or in proliferation of flutamide treated YHR+ mice suggesting that other factors may be involved in the decrease in LC number. Together, these results suggest that high neonatal testosterone is not sufficient to inhibit LC development.