PMID- 29080672
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20201209
IS  - 1095-6867 (Electronic)
IS  - 0018-506X (Linking)
VI  - 97
DP  - 2018 Jan
TI  - Fezf1 is a novel regulator of female sex behavior in mice.
PG  - 94-101
LID - S0018-506X(17)30162-9 [pii]
LID - 10.1016/j.yhbeh.2017.10.010 [doi]
AB  - Female sexual behavior is a complex process regulated by multiple brain circuits 
      and influenced by sex steroid hormones acting in the brain. Several regions in 
      the hypothalamus have been implicated in the regulation of female sexual behavior 
      although a complete circuitry involved in female sexual behavior is not 
      understood. Fez family zinc finger 1 (Fezf1) gene is a brain specific gene that 
      has been mostly studied in the context of olfactory development, although in a 
      recent study, FEZF1 has been identified as one of the genes responsible for the 
      development of Kallman syndrome. In the present study, we utilized shRNA approach 
      to downregulate Fezf1 in the ventromedial nucleus of the hypothalamus (VMN) with 
      the aim to explore the role of this gene. Adult female mice were stereotaxically 
      injected with lentiviral vectors encoding shRNA against Fezf1 gene. Mice injected 
      with shRNA against Fezf1 had significantly reduced female sexual behavior, 
      presumably due to the downregulation of estrogen receptor alpha (ERalpha), as the 
      number of ERalpha-immunoreactive cells in the VMN of Fezf1 mice was significantly 
      lower in comparison to controls. However, no effect on body weight or physical 
      activity was observed in mice with downregulated Fezf1, suggesting that the role 
      of Fezf1 in the VMN is limited to the regulation of sexual behavior. SIGNIFICANCE 
      STATEMENT: Fezf1 gene has been identified in the present study as a regulator of 
      female sexual behavior in mice. Regulation of the female sexual behavior could be 
      through the regulation of estrogen receptor alpha expression in the ventromedial 
      nucleus of the hypothalamus, as the expression of this receptor was reduced in 
      mice with downregulated Fezf1. As expression of Fezf1 is very specific in the 
      brain, this gene could present a potential target for the development of novel 
      drugs regulating hypoactive sexual desire disorder in women, if similar function 
      of FEZF1 will be confirmed in humans.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Budefeld, Tomaz
AU  - Budefeld T
AD  - Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, 
      Gerbiceva 60, 1000 Ljubljana, Slovenia.
FAU - Spanic, Tanja
AU  - Spanic T
AD  - Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, 
      Gerbiceva 60, 1000 Ljubljana, Slovenia.
FAU - Vrecl, Milka
AU  - Vrecl M
AD  - Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, 
      Gerbiceva 60, 1000 Ljubljana, Slovenia.
FAU - Majdic, Gregor
AU  - Majdic G
AD  - Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, 
      Gerbiceva 60, 1000 Ljubljana, Slovenia; Institute of Physiology, Medical School, 
      University of Maribor, Maribor, Slovenia. Electronic address: 
      gregor.majdic@vf.uni-lj.si.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171114
PL  - United States
TA  - Horm Behav
JT  - Hormones and behavior
JID - 0217764
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Fezf1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Animals
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Down-Regulation
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Female
MH  - Mice
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - RNA, Small Interfering
MH  - Repressor Proteins
MH  - Sexual Behavior, Animal/*physiology
MH  - Ventromedial Hypothalamic Nucleus/*metabolism
OTO - NOTNLM
OT  - Estrogen receptor alpha
OT  - Female sexual behavior
OT  - Fezf1
OT  - Lordosis
OT  - Mouse
EDAT- 2017/10/31 06:00
MHDA- 2018/12/12 06:00
CRDT- 2017/10/30 06:00
PHST- 2017/04/26 00:00 [received]
PHST- 2017/09/26 00:00 [revised]
PHST- 2017/10/24 00:00 [accepted]
PHST- 2017/10/31 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/10/30 06:00 [entrez]
AID - S0018-506X(17)30162-9 [pii]
AID - 10.1016/j.yhbeh.2017.10.010 [doi]
PST - ppublish
SO  - Horm Behav. 2018 Jan;97:94-101. doi: 10.1016/j.yhbeh.2017.10.010. Epub 2017 Nov 
      14.