PMID- 33622350
OWN - NLM
STAT- MEDLINE
DCOM- 20211029
LR  - 20211104
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 19
IP  - 1
DP  - 2021 Feb 23
TI  - Downregulation of TTF1 in the rat hypothalamic ARC or AVPV nucleus inhibits Kiss1 
      and GnRH expression, leading to puberty delay.
PG  - 30
LID - 10.1186/s12958-021-00710-7 [doi]
LID - 30
AB  - BACKGROUND: TTF1 is a transcription factor that is expressed in the hypothalamus 
      after birth and plays crucial roles in pubertal development. TTF1 may regulate 
      the expression of the Kiss1 gene, which may drive puberty onset in the 
      hypothalamic arcuate (ARC) and anterior ventral paraventricular (AVPV) nuclei. 
      METHODS: A dual-luciferase reporter assay was used to detect binding between TTF1 
      and the Kiss1 gene promoter. To investigate the effects of TTF1, we modified TTF1 
      expression in cell lines and in the ARC or AVPV nucleus of 21-day-old female rats 
      via lentivirus infection. TTF1 and other puberty onset-related genes were 
      detected by qRT-PCR and western blot analyses. RESULTS: The in vitro data 
      indicated that TTF1 knockdown (KD) significantly reduced Kiss1 and GnRH 
      expression. Overexpression (OE) of TTF1 promoted Kiss1 expression. In vivo, the 
      expression of Kiss1 and GnRH decreased significantly in the rats with 
      hypothalamic ARC- or AVPV-specific TTF1 KD. The TTF1-KD rats showed vaginal 
      opening delay. H&E staining revealed that the corpus luteum was obviously reduced 
      at the early puberty and adult stages in the rats with ARC- or AVPV-specific TTF1 
      KD. CONCLUSION: TTF1 bound to the promoter of the Kiss1 gene and enhanced its 
      expression. For 21-day-old female rats, decreased TTF1 in the hypothalamic ARC or 
      AVPV nucleus resulted in delayed vaginal opening and ovarian abnormalities. These 
      observations suggested that TTF1 regulates puberty onset by promoting the 
      expression of Kiss1 and plays an important role in gonad development.
FAU - Zang, Shaolian
AU  - Zang S
AD  - Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong 
      University, Shanghai, 200062, People's Republic of China.
FAU - Yin, Xiaoqin
AU  - Yin X
AD  - Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong 
      University, Shanghai, 200062, People's Republic of China.
FAU - Li, Pin
AU  - Li P
AD  - Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong 
      University, Shanghai, 200062, People's Republic of China. lipin2019@126.com.
LA  - eng
GR  - 81871131/National Natural Science Foundation of China (CN)/
GR  - 20YF1440700/Shanghai Science and Technology Development Foundation/
PT  - Journal Article
DEP - 20210223
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (Kiss1 protein, rat)
RN  - 0 (Kisspeptins)
RN  - 0 (Nkx2-1 protein, rat)
RN  - 0 (Thyroid Nuclear Factor 1)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/metabolism
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Female
MH  - Gonadotropin-Releasing Hormone/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Hypothalamus/*metabolism
MH  - Hypothalamus, Anterior/metabolism
MH  - Kisspeptins/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sexual Maturation/*genetics
MH  - Thyroid Nuclear Factor 1/*genetics/metabolism
MH  - Time Factors
PMC - PMC7901190
OTO - NOTNLM
OT  - Gonadotropin-releasing hormone (GnRH)
OT  - Kiss1
OT  - Puberty
OT  - RNA interference (RNAi)
OT  - Stereotaxic injection
OT  - Thyroid-specific transcription factor 1 (TTF1)
COIS- The authors declare that they have no competitive interests.
EDAT- 2021/02/25 06:00
MHDA- 2021/10/30 06:00
PMCR- 2021/02/23
CRDT- 2021/02/24 05:32
PHST- 2020/07/21 00:00 [received]
PHST- 2021/02/12 00:00 [accepted]
PHST- 2021/02/24 05:32 [entrez]
PHST- 2021/02/25 06:00 [pubmed]
PHST- 2021/10/30 06:00 [medline]
PHST- 2021/02/23 00:00 [pmc-release]
AID - 10.1186/s12958-021-00710-7 [pii]
AID - 710 [pii]
AID - 10.1186/s12958-021-00710-7 [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2021 Feb 23;19(1):30. doi: 10.1186/s12958-021-00710-7.