PMID- 11698654
OWN - NLM
STAT- MEDLINE
DCOM- 20020108
LR  - 20220408
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 24
DP  - 2001 Nov 20
TI  - Estrogen action and male fertility: roles of the sodium/hydrogen exchanger-3 and 
      fluid reabsorption in reproductive tract function.
PG  - 14132-7
AB  - Estrogen receptor alpha (ER alpha) is essential for male fertility. Its activity 
      is responsible for maintaining epithelial cytoarchitecture in efferent ductules 
      and the reabsorption of fluid for concentrating sperm in the head of the 
      epididymis. These discoveries and others have helped to establish estrogen's 
      bisexual role in reproductive importance. Reported here is the molecular 
      mechanism to explain estrogen's role in fluid reabsorption in the male 
      reproductive tract. It is shown that estrogen regulates expression of the 
      Na(+)/H(+) exchanger-3 (NHE3) and the rate of (22)Na(+) transport, sensitive to 
      an NHE3 inhibitor. Immunohistochemical staining for NHE3, carbonic anhydrase II 
      (CAII), and aquaporin-I (AQP1) was decreased in ER alpha knockout (alpha ERKO) 
      efferent ductules. Targeted gene-deficient mice were compared with alpha ERKO, 
      and the NHE3 knockout and CAII-deficient mice showed alpha ERKO-like fluid 
      accumulation, but only the NHE3 knockout and alpha ERKO mice were infertile. 
      Northern blot analysis showed decreases in mRNA for NHE3 in alpha ERKO and 
      antiestrogen-treated mice. The changes in AQP1 and CAII in alpha ERKO seemed to 
      be secondary because of the disruption of apical cytoarchitecture. Ductal 
      epithelial ultrastructure was abnormal only in alpha ERKO mice. Thus, in the 
      male, estrogen regulates one of the most important epithelial ion transporters 
      and maintains epithelial morphological differentiation in efferent ductules of 
      the male, independent of its regulation of Na(+) transport. Finally, these data 
      raise the possibility of targeting ER alpha in developing a contraceptive for the 
      male.
FAU - Zhou, Q
AU  - Zhou Q
AD  - Department of Veterinary Biosciences, University of Illinois, Urbana, IL 61802, 
      USA.
FAU - Clarke, L
AU  - Clarke L
FAU - Nie, R
AU  - Nie R
FAU - Carnes, K
AU  - Carnes K
FAU - Lai, L W
AU  - Lai LW
FAU - Lien, Y H
AU  - Lien YH
FAU - Verkman, A
AU  - Verkman A
FAU - Lubahn, D
AU  - Lubahn D
FAU - Fisher, J S
AU  - Fisher JS
FAU - Katzenellenbogen, B S
AU  - Katzenellenbogen BS
FAU - Hess, R A
AU  - Hess RA
LA  - eng
SI  - GENBANK/M85300
SI  - GENBANK/S83406
SI  - RefSeq/NM_007472
GR  - R01 52358/PHS HHS/United States
GR  - R01HD35126/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20011106
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Aqp1 protein, mouse)
RN  - 0 (Aquaporins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Slc9a3 protein, mouse)
RN  - 0 (Sodium-Hydrogen Exchanger 3)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 059QF0KO0R (Water)
RN  - 146410-94-8 (Aquaporin 1)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 63231-63-0 (RNA)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Absorption
MH  - Animals
MH  - Aquaporin 1
MH  - Aquaporins/genetics/metabolism
MH  - Base Sequence
MH  - Carbonic Anhydrase II/metabolism
MH  - DNA, Complementary
MH  - Estradiol/*analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogen Receptor alpha
MH  - Estrogens/*metabolism
MH  - Fertility/*physiology
MH  - Fulvestrant
MH  - Gene Expression
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - RNA
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Sodium/*metabolism
MH  - Sodium-Hydrogen Exchanger 3
MH  - Sodium-Hydrogen Exchangers/genetics/metabolism/*physiology
MH  - Vas Deferens/metabolism/*physiology
MH  - Water/metabolism
PMC - PMC61180
EDAT- 2001/11/08 10:00
MHDA- 2002/01/10 10:01
PMCR- 2002/05/20
CRDT- 2001/11/08 10:00
PHST- 2001/11/08 10:00 [pubmed]
PHST- 2002/01/10 10:01 [medline]
PHST- 2001/11/08 10:00 [entrez]
PHST- 2002/05/20 00:00 [pmc-release]
AID - 241245898 [pii]
AID - 2458 [pii]
AID - 10.1073/pnas.241245898 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14132-7. doi: 
      10.1073/pnas.241245898. Epub 2001 Nov 6.