Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells.
Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) alpha and beta was assessed, an induction of ERbeta by DES was found predominantly in PRL cells. However, since these effects were abolished in ERalpha knockout mice, DES appears to act primarily through ERalpha. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10-15 days, and Pit-1-positive cells were increased at 5-15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells.
Division of Histology and Cell Biology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan.
Keiko
K
Shukuwa
Shin-Ichi
S
Izumi
Yoshitaka
Y
Hishikawa
Kuniaki
K
Ejima
Satoshi
S
Inoue
Masami
M
Muramatsu
Yasuyoshi
Y
Ouchi
Takashi
T
Kitaoka
Takehiko
T
Koji
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015342:DNA Probes; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D050817:Transcription Factor Pit-1 / Q000502:physiology
D015342:DNA Probes; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006062:Gonadotropins; D019394:Ki-67 Antigen; D050817:Transcription Factor Pit-1; D004054:Diethylstilbestrol; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone