Antisense oligonucleotide blocks progesterone-induced lordosis behavior in ovariectomized rats.
Antisense oligonucleotides were utilized to interfere with the synthesis of progesterone receptor. A specific aODN was shown to decrease significantly the levels of PR in the T47D cell line known to express the PR gene. The molecule described was proved to be effective in hindering the effect of progesterone on target gene expression in T47D cells. The aODN was then utilized in an in vivo study to test its efficacy on the female rat sex behavior. Its injection in the ventromedial hypothalamus significantly inhibited the estrous responsiveness induced by progesterone. This study provides a clear demonstration of the full involvement of PR in the manifestation of lordosis behavior and demonstrates the activity of an aODN as antiprogestative.
Pollio
G
G
Institute of Pharmacological Sciences, University of Milan, Italy.
Xue
P
P
Zanisi
M
M
Nicolin
A
A
Maggi
A
A
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D011187:Posture; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol