PMID- 12834913
OWN - NLM
STAT- MEDLINE
DCOM- 20030908
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 978
IP  - 1-2
DP  - 2003 Jul 18
TI  - Immediate and residual effects of tamoxifen and ethynylestradiol in the female 
      rat hypothalamus.
PG  - 185-93
AB  - Very little is known about the impact of selective estrogen receptor modulators 
      (SERMs) on the brain. We examined the effects of tamoxifen (TAMOX) and the 
      synthetic estrogen 17alpha-ethynylestradiol (EE) on estrogen-dependent gene 
      expression and receptor binding in the female rat brain. Both immediate and 
      residual effects were examined in both the presence and absence of 
      17beta-estradiol. Two groups of adult, ovariectomized, female rats (n=30 per 
      group) were injected with TAMOX (5 mg/kg), EE (0.1 mg/kg), or sesame oil daily 
      for 14 days. Animals from the first group were implanted with blank or 
      17beta-estradiol Silastic capsules concurrently with the last three SERM 
      injections (immediate, group 1). Animals from the second group received either 
      blank or 17beta-estradiol implants 2 weeks after the last injection (residual, 
      group 2). All animals were sacrificed 72 h after implantation. TAMOX increased 
      uterine weight in the absence of estrogen, but inhibited uterine weight gain in 
      the presence of estrogen in both groups 1 and 2. TAMOX and EE increased oxytocin 
      receptor binding in the ventromedial nucleus of the hypothalamus (VMN) in the 
      absence of estrogen in both groups 1 and 2. The estrogen-dependent induction of 
      PR mRNA expression in the VMN was significantly attenuated by TAMOX in group 1. 
      Finally, TAMOX and EE had opposite effects on ERbeta mRNA expression in the 
      paraventricular nucleus in the absence of 17beta-estradiol in group 1. Neither 
      had any effect in group 2 when 17beta-estradiol was present. These results 
      suggest that TAMOX has mixed agonist/antagonist effects in the female rat brain, 
      many of which persist at least 2 weeks after the administration ceases.
FAU - Patisaul, Heather B
AU  - Patisaul HB
AD  - NSF Center for Behavioral Neuroscience, Emory University, Atlanta, GA 30329, USA. 
      hbeaupr@emory.edu
FAU - Aultman, Eleni A
AU  - Aultman EA
FAU - Bielsky, Isadora F
AU  - Bielsky IF
FAU - Young, Larry J
AU  - Young LJ
FAU - Wilson, Mark E
AU  - Wilson ME
LA  - eng
GR  - HD 38917/HD/NICHD NIH HHS/United States
GR  - RR 00165/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Estradiol Congeners)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Oxytocin)
RN  - 0 (Receptors, Progesterone)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 114056-26-7 (vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic 
      acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2)
RN  - 423D2T571U (Ethinyl Estradiol)
RN  - W6S6URY8OF (Vasotocin)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Binding Sites
MH  - Drug Administration Schedule/veterinary
MH  - Estradiol Congeners/adverse effects/pharmacology
MH  - Estrogen Antagonists/adverse effects/pharmacology
MH  - Ethinyl Estradiol/adverse effects/*pharmacology
MH  - Fallopian Tubes/drug effects
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Hypothalamus/*drug effects/metabolism
MH  - In Situ Hybridization
MH  - Organ Size/drug effects
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Oxytocin/genetics/metabolism
MH  - Receptors, Progesterone/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Tamoxifen/adverse effects/*pharmacology
MH  - Time Factors
MH  - Vasotocin/*analogs & derivatives/pharmacokinetics
EDAT- 2003/07/02 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - S0006899303028075 [pii]
AID - 10.1016/s0006-8993(03)02807-5 [doi]
PST - ppublish
SO  - Brain Res. 2003 Jul 18;978(1-2):185-93. doi: 10.1016/s0006-8993(03)02807-5.