PMID- 7515764
OWN - NLM
STAT- MEDLINE
DCOM- 19940713
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 54
IP  - 12
DP  - 1994 Jun 15
TI  - Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of 
      uterine insulin-like growth factor binding protein 3 gene expression.
PG  - 3115-9
AB  - We have recently shown that uterine insulin-like growth factor I (IGF-I) gene 
      expression is up-regulated by tamoxifen, a uterotrophic partial antagonist to the 
      estrogen receptor, but down-regulated by the complete estrogen receptor 
      antagonist ICI 182780, which causes uterine involution. This result is consistent 
      with prior reports indicating that the uterotrophic effects of estradiol are 
      mediated at least in part by estradiol-stimulated uterine IGF-I gene expression. 
      We demonstrate here that the uterotrophic agents estradiol and tamoxifen each 
      suppress expression of the IGF binding protein 3 (IGFBP-3) gene in uterus to less 
      than one-third of control values, while oophorectomy or administration of the 
      complete estrogen receptor antagonist ICI 182780, both of which result in uterine 
      involution, are associated with a greater than 3-fold stimulation of uterine 
      IGFBP-3 gene expression. The data reveal a negative correlation between uterine 
      weight and uterine IGFBP-3 gene expression as well as reciprocal regulation by 
      estradiol of expression in uterus of the genes encoding IGF-I and IGFBP-3. In 
      vitro, IGFBP-3 protein accumulation in media conditioned by primary uterine 
      cultures was decreased by estradiol treatment and increased by ICI 182780 
      treatment. Together, these observations provide a novel mechanism by which 
      estradiol and antiestrogens modulate uterine IGF-I physiology that is consistent 
      with the view that the mitogenic activity of IGF-I is reduced in the presence of 
      IGFBP-3. The uterotrophic toxicity of chronic estradiol or tamoxifen treatment 
      may be causally related to both the inhibition of uterine IGFBP-3 expression and 
      the stimulation of uterine IGF-I expression by these compounds.
FAU - Huynh, H
AU  - Huynh H
AD  - Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.
FAU - Pollak, M
AU  - Pollak M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Carrier Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
GS  - IGF-I
GS  - IGFBP-3
MH  - Animals
MH  - Carrier Proteins/blood/*genetics
MH  - Cells, Cultured
MH  - Culture Techniques
MH  - Estradiol/*pharmacology
MH  - Estrogen Replacement Therapy
MH  - Female
MH  - Gene Expression/drug effects
MH  - Hypophysectomy
MH  - Insulin-Like Growth Factor Binding Proteins
MH  - Organ Size/drug effects
MH  - Ovariectomy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tamoxifen/*pharmacology
MH  - Uterus/*drug effects/*metabolism
EDAT- 1994/06/15 00:00
MHDA- 1994/06/15 00:01
CRDT- 1994/06/15 00:00
PHST- 1994/06/15 00:00 [pubmed]
PHST- 1994/06/15 00:01 [medline]
PHST- 1994/06/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1994 Jun 15;54(12):3115-9.