Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman.
BACKGROUND
Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology.


METHODS
We analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17beta-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17beta-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene.


RESULTS
A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation.


CONCLUSIONS
At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.
Jelinsky
Scott A
SA
Biological Technologies, Wyeth Research, Cambridge, USA. sjelinsky@wyeth.com
Choe
Sung E
SE
Crabtree
Judy S
JS
Cotreau
Monette M
MM
Wilson
Ewa
E
Saraf
Kathryn
K
Dorner
Andrew J
AJ
Brown
Eugene L
EL
Peano
Bryan J
BJ
Zhang
Xiaochun
X
Winneker
Richard C
RC
Harris
Heather A
HA