Estrogen receptor-{alpha} antisense decreases brain estrogen receptor levels and affects ventilation in male and female rats

October 17, 2001

Report Among the Highlighted Topics on Gender Differences in the October Edition of the Journal of Applied Physiology

BETHESDA, Md. -- October 18, 2001 -- The American Physiological Society (APS) kicks off a special series entitled, "Highlighted Topics on Gender Differences in Physiology," beginning with the October 2001 edition of the Journal of Applied Physiology, the Society's flagship publication. The October issue offers the following examination:

Estrogen Receptor-{alpha} Antisense Decreases Brain Estrogen Receptor Levels and Affects Ventilation in Male and Female Rats
The finding that "Estrogen receptor-{alpha} antisense decreases brain estrogen receptor levels and affects ventilation in male and female rats," is the result of an investigation conducted by Shashita R. Inamdar, Kathleen M. Eyster, and Evelyn H. Schlenker, all of the Division of Basic Biomedical Sciences at the University of South Dakota School of Medicine, Vermillion, SD.

Dr. Inamdar and colleagues explored the effects of estrogen receptor-{alpha}protein production in the brain of neonatal rats on the gender-specific ventilatory response to aspartic acid. To determine whether the activational effects of puberty modified these responses to aspartic acid the investigators evaluated animals shortly after weanling (~23 days old) and at adulthood (2-3 months old).

Background, Methodology and Findings
These investigators found that, during the late fetal and early neonatal period, estrogen receptors are more widely and abundantly expressed compared with that shown during adulthood. This is of great importance because the late fetal and early neonatal periods coincide with the critical developmental period when major organizational changes take place in the neuronal circuitry of the brain. Thus changes in ER expression during this stage can influence the growth and pattern of differentiation of the developing rat brain and may have enduring consequences into adulthood.

A novel molecular technique employed in the present study involves the use of antisense oligodeoxynucleotide against estrogen receptors. Such antisense oligodeoxynucleotides are short sequences of DNA or RNA, usually 12-15 bases in length, that are complementary to a specific gene and inhibit the expression of the gene and thus the protein that would normally be produced. The investigators found that aspartic acid decreased 65 percent at six hours and 35 percent at 24 hours after antisense oligodeoxynucleotide exposure. Weanling estrogen receptor oligodeoxynucleotide-treated rats were shorter and weighed less than controls. Only adult estrogen receptor oligodeoxynucleotide-treated males exhibited these traits.

These results indicated that neonatal estrogen receptors affect aspartic acid modulation of breathing and body growth in a gender-specific and developmental manner.
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.


Contact: Donna Krupa:
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American Physiological Society

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