Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens.

Abstract

The antiestrogens MER-25, CI-628, and nafoxidine inhibit the uptake of [3H]-estradiol in whole homogenates and isolated cell nuclei tissues and the pituitary, and inhibit estradiol-induced female sexual behavior. The antiestrogens were injected intraperitoneally 2 h prior to an intravenous injection of [3H]estradiol, and the animals were killed 2 h after the estradiol. CI-628 reduces radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area -septum and pituitary. Nafoxidine reduces uptake in cell nuclei of the hypothalamus, preoptic area-septum and pituitary. In this paradigm, MER-25 inhibited uptake only in the pituitary. In the analogous behavioral experiments, with antiestrogens injected 2 h prior to an intravenous injection of unesterified estradiol, CI-628 and nafoxidine totally inhibited lordosis responding. MER-25 shows no inhibition of behavior in this paradigm. However, when MER-25 is injected 12 h prior to the estradiol, it inhibits retention of [3H]estradiol at 2 h in brain and pituitary cell nuclei, and lordosis responding is also inhibited. Additionally, the antiestrogens can apparently displace previously bound [3H]estrdiol. When the antiestrogens are injected 2 h prior to an injection of [3H]estradiol, MER-25, CI-628 and nafoxidine all show greater inhibition of nuclear estradiol retention at 12 h after the [3H]estradiol injection than 2 h. Analogously, when CI-628 is injected 2 h after an intravenous injection of [3H]estradiol, it displaces most of the radioactivity present in hypothalamic-preoptic area nuclei at 12 h after the estradiol injection. These results indicate that antiestrogens can prevent or reverse the nuclear concentration of estradiol in brain cells and are consistent with a role of the cell nucleus in the induction of estrous behavior by estradiol.

• Authors: E J Roy, G N Wade
• Journal: Brain research (Brain Res) Vol. 126 Issue 1 Pg. 73-87 (Apr 22 1977) ISSN: 0006-8993 [Print] Netherlands
• PMID: 856418 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Estrogen Antagonists
• Nafoxidine
• Estradiol
• Nitromifene
• Ethamoxytriphetol

Topics

• Animals
• Brain (drug effects, metabolism)
• Cell Nucleus (metabolism)
• Cerebral Cortex (metabolism)
• Estradiol (metabolism, pharmacology)
• Estrogen Antagonists
• Ethamoxytriphetol (pharmacology)
• Female
• Hypothalamus (metabolism)
• Nafoxidine (pharmacology)
• Nitromifene (pharmacology)
• Pituitary Gland (drug effects, metabolism)
• Posture
• Preoptic Area (metabolism)
• Rats
• Sexual Behavior, Animal (drug effects)
• Time Factors