Regulated and Functional Expression of the Corepressor MTA3 in Rodent Testis.
Metastasis-associated protein (MTA)3 is a subunit of the Mi-2/nucleosome remodeling and deacetylase protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive. We, therefore, document here for the first time the expression of Mta3/MTA3 in mammalian testes, where MTA3 protein was identified mainly in interstitial Leydig cells. Testicular levels of Mta3/MTA3 were overtly modulated by pituitary gonadotropins, as well as metabolic signals, such as dexamethasone, T4, and rosiglitazone. In addition, ablation of endogenous Mta3 by short hairpin RNA significantly inhibited human choriogonadotropin/dibutyryl-cAMP (db-cAMP)-stimulated progesterone secretion in MA-10 Leydig cells, whereas overexpression of exogenous MTA3 effectively reversed Mta3 deficiency damaged progesterone production. Moreover, attenuated Mta3 expression positively correlated to the deregulated level of serum testosterone in murine type 2 diabetes mellitus. From a functional standpoint, MTA3 deficiency was involved in insulin-mediated inhibition of testicular steroidogenesis. Our data are the first to disclose the presence and functional role of MTA3 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues and is closely associated with steroidogenic dysfunction. The current study expands the reproductive dimension of MTA3, which may operate directly at the testicular level to modulate steroidogenic function.
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Ke
K
He
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Hu
H
Qu
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Hui
H
Wang
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Shun
S
Zhang
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Xin-Hong
XH
Qian
Department of Obstetrics and Gynecology/Reproductive Medical Center (K.H.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China; Department of Urology/Reproductive Medicine Research Center (H.Q.), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, People's Republic of China; and Departments of Medical Psychology (H.W.), Department of Gynecology and Obstetrics (S.Z.), Reproductive Medicine Center, Tangdu Hospital, Department of Pediatrics (X.-h.Q.), Xijing Hospital, and Department of Histology and Embryology (W.L.), Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Wei
W
Li
D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D051381:Rats; D000077154:Rosiglitazone; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D045162:Thiazolidinediones / Q000494:pharmacology
D006063:Chorionic Gonadotropin; C435499:Mta3 protein, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013739:Testosterone; D011374:Progesterone; D003907:Dexamethasone; D000242:Cyclic AMP