Effects of metoclopramide on mRNA levels of steroid 5á-reductase isozymes in prostate of adult rats

ABSTRACT

The rising incidence of prostate cancer and benign prostatic hypertrophy in the Western world is a cause of increasing public health concern. The most active androgen in the prostate is 5á-dihydrotestosterone obtained from testosterone (T) by the enzyme 5á-reductase (5á-R), expressed in the prostate as two isozymes, 5á-R1 and 5á-R2. These isozymes are involved in the growth and development of normal prostate and in the onset and progression of prostate disease. Besides androgens, prolactin (PRL) may also play a role, although it is not clear whether its effects on the prostate are in synergism with or independent of those of androgens. We previously demonstrated that sulpiride, an inductor of hyperprolactinemia, increased mRNA levels of 5á-R isozymes in prostate of adult rat. We hypothesized a possible interrelationship between PRL levels and 5á-R, although the effects of sulpiride per se cannot be ruled out. In the present study, one-step quantitative reverse transcription polymerase chain reaction coupled with laser-induced fluorescence capillary electrophoresis was used to quantify mRNA levels of both 5á-R isozymes in prostate of adult rat after administration of metoclopramide (MTC), another inductor of PRL secretion. With the administration regimens studied, MTC produced an increase in prostate weight and mRNA levels of 5á-R1 and 5á-R2 in adult rats. Given our finding that MTC per se or MTC-induced hyperprolactinemia modifies prostate disease-related parameters in animals with reduced plasma T levels, further investigation is warranted into the possibility that MTC use by aging males may increase their risk of prostate disease (AU)