PMID- 28250236
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20180609
IS  - 1741-7899 (Electronic)
IS  - 1470-1626 (Linking)
VI  - 153
IP  - 5
DP  - 2017 May
TI  - TGFB1 represses the expression of SF1 and LRH1 to inhibit E(2) production in rat 
      LCs.
PG  - 621-629
LID - 10.1530/REP-16-0044 [doi]
AB  - Leydig cells (LCs) in the adult testis have been identified as the major sites of 
      oestrogen production, which is crucial for mammalian germ cell differentiation. 
      Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits 
      estradiol (E(2)) secretion via down-regulating Cyp19 gene expression in mature 
      rat LCs. However, the mechanism remains unclear. In the present study, the 
      effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver 
      receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP 
      responsive element modulator (CREM) were evaluated both in primary cultured LCs 
      and in rat testis. The involvement of TGFB1 signalling in the regulation of SF1 
      and LRH1 expression was then validated by applying the inhibitor of the TGFB type 
      1 receptor (TGFBR1) SB431542. Moreover, the expression of CYP19 in testicular LCs 
      was investigated and the production of E(2) in testicular interstitial fluid 
      (TIF) was measured. The results showed that TGFB1 especially down-regulated the 
      expression levels of SF1 and LRH1 both in primary cultured LCs and in rat testis. 
      The down-regulations of TGFB1 in the production of E(2) in TIF and the expression 
      of CYP19 in testicular LCs were also observed in vivo These inhibitory effects 
      could be reversed by TGFBR1 inhibitor SB431542. Our findings suggest that TGFB1 
      may act through the canonical signalling pathway involving ALK5 to restrain SF1 
      and LRH1 accumulation and eventually attenuate Cyp19 transcription and oestrogen 
      production in LCs.
CI  - (c) 2017 Society for Reproduction and Fertility.
FAU - Yang, Qianqian
AU  - Yang Q
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China.
AD  - Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military 
      Medical University, Xi'an, Shaanxi, People's Republic of China.
FAU - Ma, Binfang
AU  - Ma B
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China.
FAU - Qiao, Huilian
AU  - Qiao H
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China.
FAU - Ma, He
AU  - Ma H
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China.
FAU - Dong, Yuhang
AU  - Dong Y
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China.
FAU - Cao, Liang
AU  - Cao L
AD  - Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military 
      Medical University, Xi'an, Shaanxi, People's Republic of China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military 
      Medical University, Xi'an, Shaanxi, People's Republic of China jingma@fmmu.edu.cn 
      lizhenhe@fmmu.edu.cn.
FAU - Li, Zhen
AU  - Li Z
AD  - Department of Histology and EmbryologyThe Fourth Military Medical University, 
      Xi'an, Shaanxi, People's Republic of China jingma@fmmu.edu.cn 
      lizhenhe@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170301
PL  - England
TA  - Reproduction
JT  - Reproduction (Cambridge, England)
JID - 100966036
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (NR5A2 protein, rat)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Steroidogenic Factor 1)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (steroidogenic factor 1, rat)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/*antagonists & inhibitors/metabolism
MH  - Estradiol/*metabolism
MH  - Leydig Cells/cytology/drug effects/*metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cytoplasmic and Nuclear/*antagonists & inhibitors/metabolism
MH  - Steroidogenic Factor 1/*antagonists & inhibitors/metabolism
MH  - Testis/cytology/drug effects/*metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
EDAT- 2017/03/03 06:00
MHDA- 2017/11/01 06:00
CRDT- 2017/03/03 06:00
PHST- 2016/01/24 00:00 [received]
PHST- 2017/02/10 00:00 [revised]
PHST- 2017/02/28 00:00 [accepted]
PHST- 2017/03/03 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2017/03/03 06:00 [entrez]
AID - REP-16-0044 [pii]
AID - 10.1530/REP-16-0044 [doi]
PST - ppublish
SO  - Reproduction. 2017 May;153(5):621-629. doi: 10.1530/REP-16-0044. Epub 2017 Mar 1.