Prostate gland growth during development is stimulated in both male and female rat fetuses by intrauterine proximity to female fetuses

In rodents, steroid hormones are transported between adjacent fetuses, and male or female fetuses that develop in utero between female fetuses (2F mal es or 2F females) have higher serum levels of estradiol and lower serum lev els of testosterone relative to siblings of the same sex that develop betwe en two male fetuses (2M males or 2M females). The present study was prompte d by the prior unexpected finding that as adults, 2F male mice have an enla rged prostate, and increased numbers of prostatic androgen receptors relati ve to 2M males. We examined prostate development in both male and female ra t fetuses from different intrauterine positions using computer-assisted, 3- dimensional reconstruction of the urogenital complex. In males, this includ ed the prostate, seminal vesicles and utricle (a remnant of the Mullerian d ucts), while in females it included development of prostatic glandular buds . The mean cross-sectional area of developing prostatic epithelial buds, ut ricle and seminal vesicles was significantly increased in 2F male relative to 2M male fetuses. In female fetuses, prostatic bud development was signif icant;ly more likely to occur in 2F (67%) than in 2M (29%) animals. These f indings suggest that, the transport of a small supplement of estrogen from adjacent female fetuses enhances androgen-dependent accessory organ develop ment. We also found that mRNAs encoding receptors for both estrogen and and rogen were located in the mesenchyme of the developing male prostate. The l ocalization of estrogen and androgen receptor mRNA in this region further s uggests that the mesenchymal induction of prostatic epithelial growth invol ves both hormones. The cranial dorsolateral prostatic buds exhibited the gr eatest enlargement in 2F males. This region of the developing prostate in r ats is comparable (that is the embryonic homologue) to the region exhibitin g benign prostatic hyperplasia (BPH) during aging in men. We propose that t he potential for pathological regrowth of the prostate during aging is impr inted by estradiol during fetal development.