Chronic estrogenic drug treatment increases preproenkephalin mRNA levels in the rat striatum and nucleus accumbens.
Estrogens modulate the expression of preproenkephalin (PPE) in the hypothalamus but little is known for other brain regions. The present study investigated the effect of hormonal withdrawal and replacement therapy on PPE expression in the striatum, nucleus accumbens and cortex. Ovariectomized Sprague-Dawley rats were treated for 2 weeks with estradiol, a specific ligand for estrogen receptor alpha (ERalpha), 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and estrogen receptor beta (ERbeta) 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), or the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. Brain PPE mRNA levels, measured by in situ hybridization, were high in the striatum and nucleus accumbens compared to the low expression in the cortex. Ovariectomy decreased uterine weights compared to intact uterus, which was corrected by estradiol and PPT. Tamoxifen and raloxifene partially stimulated uterine weights while DPN left it unchanged. In the anterior, median and posterior striatum and in the core and shell of the nucleus accumbens, ovariectomy decreased PPE mRNA levels compared to intact rats, this was corrected by estradiol treatment except for the posterior striatum. PPT, DPN, tamoxifen and raloxifene reproduced the estradiol effect. In the prefrontal and cingulate cortices, neither ovariectomy nor treatments changed PPE mRNA levels. These results show for the first time that estradiol increases PPE mRNA in the striatum and nucleus accumbens. This effect is observed also with estrogen receptor agonists for the ERalpha and ERbeta as well as with SERMs.
Le Saux
Maryvonne
M
Molecular Endocrinology and Oncology Research Center, Faculté de Pharmacie, Laval University Medical Center (CHUL), 2705, Laurier Boulevard, Sainte-Foy, Que., Canada G1V 4G2.
Di Paolo
Thérèse
T
D000704:Analysis of Variance; D000818:Animals; D004334:Drug Administration Schedule; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000502:physiology*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size; D010052:Ovariectomy; D010636:Phenols / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D011422:Propionates
D004745:Enkephalins; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; D010636:Phenols; D011498:Protein Precursors; D011720:Pyrazoles; D012333:RNA, Messenger; D020849:Raloxifene Hydrochloride; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C033660:preproenkephalin