The change in development of cells rich in H+-ATPase induced by neonatal administration of steroids emphasizes the importance of the steroid hormone environment for maintaining the normal timing and intensity of expression of genes such as H+-ATPase and that altering the steroid environment can repress or retard their expression.
In summary, this study examined whether androgens, estrogens, or both are involved in the development of cells that are rich in H+-ATPase.
Our data show that treatment with either a potent GnRHa or estrogen (DES or EE) is sufficient to significantly reduce the expression of this protein. It is possible that these compounds induce this reduction via suppressing the hypothalamo-pituitary axis with consequent reduction in androgen levels and subsequent loss of androgen receptor protein expression or action in the reproductive tract. Because cells rich in H+-ATPase were not lost in animals treated neonatally with DES + TE, this suggests that androgens are capable of preventing some of the effects induced by DES. This role for androgens is supported by the reduction in the number of H+ATPase-rich cells observed in rats treated with the androgen receptor antagonist flutamide during postnatal development. Additional support is provided by the previous observation that flutamide treatment of the adult rat epididymis induces an increase in lumenal pH, consistent with androgen action being responsible for maintaining a low pH within the epididymis. Our data suggest that normal serum testosterone levels and functional epididymal ARs are required for normal developmental expression of H+-ATPase-rich cells in the epididymis.