TY - JOUR
T1 - Possible testosterone redundancy for 5α-dihydrotestosterone in the masculinization of mouse external genitalia
AU - Ueda, Yuko
AU - Suzuki, Kentaro
AU - Kajimoto, Mizuki
AU - Fujimoto, Kota
AU - Mahendroo, Mala
AU - Ema, Masatsugu
AU - Yamada, Gen
AU - Hara, Isao
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science KAKENHI grants 18K06837, 18K06938, 21K06822, and 21K19538.
Publisher Copyright:
© 2022 Japanese Association for Laboratory Animal Science.
PY - 2022
Y1 - 2022
N2 - The development of embryonic external genitalia (eExG) into characteristic male structures, such as urethra and penile erectile tissues, depends on 5α-dihydrotestosterone (DHT). Although the corpus cavernosum (CC) is well known as essential for erectile function in adults, its developmental process and its dependency on DHT have been unknown. To reveal the dimorphic formation of the murine CC from the embryonic stage, we first analyzed the production of the protein vascular endothelial growth factor receptor-2 (FLK1) via its expression (hereinafter referred as “expression of FLK1”) and the expression of alpha-smooth muscle actin (ACTA2) and collagen type 1 (COL1A1) in developing external genitalia. The 5-α reductase type 2 encoded by the SRD5A2 gene has been suggested to be a crucial enzyme for male sexual differentiation, as it converts testosterone (T) into DHT in the local urogenital organs. In fact, SRD5A2 mutation results in decreased synthesis of DHT, which leads to various degrees of masculinized human external genitalia (ExG). We further investigated the expression profile of SRD5A2 during the formation of the murine CC. We observed that SRD5A2 was expressed in smooth muscle of the CC. To determine the role of SRD5A2 in CC formation, we analyzed the formation of erectile tissue in the male Srd5a2 KO mice and measured the levels of androgens in the ExG by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Intriguingly, there were no obvious defects in the CCs of male Srd5a2 KO mice, possibly due to increased T levels. The current study suggests possible redundant functions of androgens in CC development.
AB - The development of embryonic external genitalia (eExG) into characteristic male structures, such as urethra and penile erectile tissues, depends on 5α-dihydrotestosterone (DHT). Although the corpus cavernosum (CC) is well known as essential for erectile function in adults, its developmental process and its dependency on DHT have been unknown. To reveal the dimorphic formation of the murine CC from the embryonic stage, we first analyzed the production of the protein vascular endothelial growth factor receptor-2 (FLK1) via its expression (hereinafter referred as “expression of FLK1”) and the expression of alpha-smooth muscle actin (ACTA2) and collagen type 1 (COL1A1) in developing external genitalia. The 5-α reductase type 2 encoded by the SRD5A2 gene has been suggested to be a crucial enzyme for male sexual differentiation, as it converts testosterone (T) into DHT in the local urogenital organs. In fact, SRD5A2 mutation results in decreased synthesis of DHT, which leads to various degrees of masculinized human external genitalia (ExG). We further investigated the expression profile of SRD5A2 during the formation of the murine CC. We observed that SRD5A2 was expressed in smooth muscle of the CC. To determine the role of SRD5A2 in CC formation, we analyzed the formation of erectile tissue in the male Srd5a2 KO mice and measured the levels of androgens in the ExG by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Intriguingly, there were no obvious defects in the CCs of male Srd5a2 KO mice, possibly due to increased T levels. The current study suggests possible redundant functions of androgens in CC development.
KW - 5-α reductase type 2
KW - 5α-dihydrotestosterone
KW - corpus cavernosum
KW - external genitalia
KW - redundancy
UR - http://www.scopus.com/inward/record.url?scp=85141495957&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141495957&partnerID=8YFLogxK
U2 - 10.1538/expanim.22-0038
DO - 10.1538/expanim.22-0038
M3 - Article
C2 - 35613877
AN - SCOPUS:85141495957
SN - 1341-1357
VL - 71
SP - 451
EP - 459
JO - Experimental Animals
JF - Experimental Animals
IS - 4
ER -