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 males or 2F females) have higher serum levels of estradiol and lower serum levels of testosterone relative to siblings of the same sex that develop between two male fetuses (2M males or 2M females). The present study was prompted by the prior unexpected finding that as adults, 2F male mice have an enlarged prostate, and increased numbers of prostatic androgen receptors relative to 2M males. We examined prostate development in both male and female rat fetuses from different intrauterine positions using computer-assisted, 3-dimensional reconstruction of the urogenital complex. In males, this included the prostate, seminal vesicles and utricle (a remnant of the Müllerian ducts), while in females it included development of prostatic glandular buds. The mean cross-sectional area of developing prostatic epithelial buds, utricle and seminal vesicles was significantly increased in 2F male relative to 2M male fetuses. In female fetuses, prostatic bud development was significantly more likely to occur in 2F (67%) than in 2M (29%) animals. These findings suggest that the transport of a small supplement of estrogen from adjacent female fetuses enhances androgen-dependent accessory organ development. We also found that mRNAs encoding receptors for both estrogen and androgen were located in the mesenchyme of the developing male prostate. The localization of estrogen and androgen receptor mRNA in this region further suggests that the mesenchymal induction of prostatic epithelial growth involves both hormones. The cranial dorsolateral prostatic buds exhibited the greatest enlargement in 2F males. This region of the developing prostate in rats is comparable (that is the embryonic homologue) to the region exhibiting benign prostatic hyperplasia (BPH) during aging in men. We propose that the potential for pathological regrowth of the prostate during aging is imprinted by estradiol during fetal development.
Timms
B G
BG
Division of Basic Biomedical Sciences, School of Medicine, University of South Dakota, Vermillion 57069, USA.
Petersen
S L
SL
vom Saal
F S
FS
D000818:Animals; D005260:Female; D005333:Fetus / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000196:embryology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D012727:Sex Characteristics
D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen