Abstract
Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgendependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.
| Original language | English |
|---|---|
| Pages (from-to) | 449-462 |
| Number of pages | 14 |
| Journal | Endocrinology |
| Volume | 155 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2014 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Endocrinology
Cite this
Bmp7 and lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in Medaka. / Ogino, Yukiko; Hirakawa, Ikumi; Inohaya, Keiji; Sumiya, Eri; Miyagawa, Shinichi; Denslow, Nancy; Yamada, Gen; Tatarazako, Norihisa; Iguchi, Taisen.
In: Endocrinology, Vol. 155, No. 2, 01.02.2014, p. 449-462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bmp7 and lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in Medaka
AU - Ogino, Yukiko
AU - Hirakawa, Ikumi
AU - Inohaya, Keiji
AU - Sumiya, Eri
AU - Miyagawa, Shinichi
AU - Denslow, Nancy
AU - Yamada, Gen
AU - Tatarazako, Norihisa
AU - Iguchi, Taisen
PY - 2014/2/1
Y1 - 2014/2/1
N2 - Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgendependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.
AB - Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgendependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.
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UR - http://www.scopus.com/inward/citedby.url?scp=84893195295&partnerID=8YFLogxK
U2 - 10.1210/en.2013-1507
DO - 10.1210/en.2013-1507
M3 - Article
C2 - 24248458
AN - SCOPUS:84893195295
VL - 155
SP - 449
EP - 462
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 2
ER -