Regulation of the epididymal glutathione peroxidase-like protein in the mouse: dependence upon androgens and testicular factors.

The protein MEP24 was previously described as a glutathione peroxidase-like molecule specifically secreted by the mouse caput epididymidis. Recently, its binding to the head of spermatozoa was demonstrated. Here, the regulation of MEP24 expression was studied by analyzing transcriptional and translational activities in the epididymis (1) of adult mice castrated on day 60 and given various substitutive testosterone (T) treatments from day 90 and (2) of hemicastrated adult animals. In castrated mice, T treatment induced a significant rise in plasma T and 5 alpha-dihydrotestosterone (DHT) concentrations that greatly exceeded the control values. Owing to efficient regulation, however, the epididymal T and DHT levels were never higher than those of the controls. The restoration of MEP24 mRNA accumulation was complete when the epididymal DHT content returned to its normal value. However, when estimated in a cell-free system, the in vitro translatable MEP24 mRNA level never exceeded 70% of control values, even though the DHT and accumulated mRNAs were restored by 100% or more. In hemicastrates, the T content was normal on the castrated side, while the DHT content exhibited a significant decrease (47%). In this case, the MEP24 mRNA accumulation reached 88% of the normal value, but the translation rate, both in vitro and in vivo, was only about 50%. Ultrastructural studies showed that the normal rough endoplasmic reticulum organization in segment I cells is dependent upon the presence of testicular fluid in the epididymal duct lumen. Thus, this report shows that the MEP24 mRNA steady-state level is completely recovered in the presence of a normal epididymal DHT content, while restoration of the regulation of translation is just partial. This could be related to the cell organization but seems mainly dependent upon the presence of specific mRNA-associated factors which are probably under the control of androgens and/or molecules carried by the testicular fluid.