PMID- 31963388
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 16
TI  - Hormonal and Molecular Regulation of Phallus Differentiation in a Marsupial 
      Tammar Wallaby.
LID - 10.3390/genes11010106 [doi]
LID - 106
AB  - Congenital anomalies in phalluses caused by endocrine disruptors have gained a 
      great deal of attention due to its annual increasing rate in males. However, the 
      endocrine-driven molecular regulatory mechanism of abnormal phallus development 
      is complex and remains largely unknown. Here, we review the direct effect of 
      androgen and oestrogen on molecular regulation in phalluses using the marsupial 
      tammar wallaby, whose phallus differentiation occurs after birth. We summarize 
      and discuss the molecular mechanisms underlying phallus differentiation mediated 
      by sonic hedgehog (SHH) at day 50 pp and phallus elongation mediated by 
      insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding 
      protein 3 (IGFBP3), as well as multiple phallus-regulating genes expressed after 
      day 50 pp. We also identify hormone-responsive long non-coding RNAs (lncRNAs) 
      that are co-expressed with their neighboring coding genes. We show that the 
      activation of SHH and IGF1, mediated by balanced androgen receptor (AR) and 
      estrogen receptor 1 (ESR1) signalling, initiates a complex regulatory network in 
      males to constrain the timing of phallus differentiation and to activate the 
      downstream genes that maintain urethral closure and phallus elongation at later 
      stages.
FAU - Chen, Yu
AU  - Chen Y
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL 32603, USA.
AD  - School of BioSciences, The University of Melbourne, Victoria 3010, Australia.
FAU - Renfree, Marilyn B
AU  - Renfree MB
AD  - School of BioSciences, The University of Melbourne, Victoria 3010, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200116
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (Androgens)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Estrogens)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Receptors, Androgen)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Androgens/metabolism
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Endocrine Disruptors
MH  - Estrogens/metabolism/pharmacology
MH  - Female
MH  - Genitalia, Female
MH  - Genitalia, Male/growth & development
MH  - Hedgehog Proteins/genetics/metabolism
MH  - Insulin-Like Growth Factor Binding Protein 3/genetics/metabolism
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Macropodidae/*growth & development/metabolism
MH  - Male
MH  - Penis/*growth & development/metabolism
MH  - Receptors, Androgen/metabolism
MH  - Sex Differentiation/*drug effects
PMC - PMC7017150
OTO - NOTNLM
OT  - IGF1
OT  - RNAseq
OT  - SHH
OT  - WGCNA
OT  - androstanediol
OT  - castration
OT  - lncRNA
OT  - marsupial
OT  - oestrogen
OT  - phallus
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/01/23 06:00
MHDA- 2020/09/30 06:00
PMCR- 2020/01/01
CRDT- 2020/01/23 06:00
PHST- 2019/12/09 00:00 [received]
PHST- 2019/12/24 00:00 [revised]
PHST- 2020/01/14 00:00 [accepted]
PHST- 2020/01/23 06:00 [entrez]
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - genes11010106 [pii]
AID - genes-11-00106 [pii]
AID - 10.3390/genes11010106 [doi]
PST - epublish
SO  - Genes (Basel). 2020 Jan 16;11(1):106. doi: 10.3390/genes11010106.