The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.
The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.
Katayama
Seiichi
S
Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Kamisu, Ibaraki 314-0255, Japan. katayama@ankaken.co.jp
Ashizawa
Koji
K
Gohma
Hiroshi
H
Fukuhara
Tadahiro
T
Narumi
Kazunori
K
Tsuzuki
Yasuhiro
Y
Tatemoto
Hideki
H
Nakada
Tadashi
T
Nagai
Kenji
K
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists* / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D004965:Estrogen Antagonists; D004967:Estrogens; D053823:Hedgehog Proteins; D009570:Nitriles; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010636:Phenols; D011422:Propionates; C000606239:Ptch1 protein, rat; D011720:Pyrazoles; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D004997:Ethinyl Estradiol; D004958:Estradiol