PMID- 17188730
OWN - NLM
STAT- MEDLINE
DCOM- 20070410
LR  - 20131121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 218
IP  - 2
DP  - 2007 Jan 15
TI  - Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: 
      developmental exposure of rats to 4-methylbenzylidene camphor.
PG  - 152-65
AB  - The developing neuroendocrine brain represents a potential target for endocrine 
      active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits 
      estrogenic activity, but also interferes with the thyroid axis. We investigated 
      effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at 
      brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered 
      in chow to the parent generation before mating, during gestation and lactation, 
      and to the offspring until adulthood. mRNA of estrogen target genes involved in 
      control of sexual behavior and gonadal functions was measured by real-time RT-PCR 
      in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of 
      adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone 
      receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in 
      a sex- and region-specific manner. In order to assess possible changes in 
      sensitivity of target genes to estrogens, offspring were gonadectomized on day 
      70, injected with estradiol (E2, 10 or 50 microg/kg s.c.) or vehicle on day 84, 
      and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h) 
      of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO, 
      whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor 
      coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data 
      indicate profound sex- and region-specific alterations in the regulation of 
      estrogen target genes at brain level. Effect patterns in baseline and E2-induced 
      gene expression differ from those in uterus and prostate.
FAU - Maerkel, Kirsten
AU  - Maerkel K
AD  - Institute of Pharmacology and Toxicology and GREEN Tox, University of Zurich, 
      CH-8057 Zurich, Switzerland.
FAU - Durrer, Stefan
AU  - Durrer S
FAU - Henseler, Manuel
AU  - Henseler M
FAU - Schlumpf, Margret
AU  - Schlumpf M
FAU - Lichtensteiger, Walter
AU  - Lichtensteiger W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061101
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Enkephalins)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Thyroid Hormones)
RN  - 4TI98Z838E (Estradiol)
RN  - 76-22-2 (Camphor)
RN  - 8I3XWY40L9 (enzacamene)
RN  - 93443-35-7 (preproenkephalin)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Brain Chemistry/*drug effects
MH  - Camphor/*analogs & derivatives/toxicity
MH  - Endocrine Disruptors/*pharmacology
MH  - Enkephalins/biosynthesis
MH  - Estradiol/pharmacology
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, src/genetics
MH  - Litter Size/drug effects
MH  - Male
MH  - Molecular Sequence Data
MH  - Orchiectomy
MH  - Organ Size/drug effects
MH  - Ovariectomy
MH  - Preoptic Area/drug effects/metabolism
MH  - Protein Precursors/biosynthesis
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, Estrogen/biosynthesis/genetics
MH  - Receptors, Progesterone/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Characteristics
MH  - Thyroid Gland/drug effects/growth & development
MH  - Thyroid Hormones/biosynthesis
MH  - Ventromedial Hypothalamic Nucleus/drug effects/metabolism
EDAT- 2006/12/26 09:00
MHDA- 2007/04/11 09:00
CRDT- 2006/12/26 09:00
PHST- 2006/07/19 00:00 [received]
PHST- 2006/10/02 00:00 [revised]
PHST- 2006/10/29 00:00 [accepted]
PHST- 2006/12/26 09:00 [pubmed]
PHST- 2007/04/11 09:00 [medline]
PHST- 2006/12/26 09:00 [entrez]
AID - S0041-008X(06)00406-6 [pii]
AID - 10.1016/j.taap.2006.10.026 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2007 Jan 15;218(2):152-65. doi: 
      10.1016/j.taap.2006.10.026. Epub 2006 Nov 1.