Progesterone, as well as 17β-estradiol, is important for regulating AHR battery homoeostasis in the rat uterus.
Several studies indicate that the aryl hydrocarbon receptor (AHR), which plays an important role in mediating the toxicity of many industrial chemicals, plays an important role in the physiology of female reproductive tract organs. This makes it likely that the AHR and additional components of the AHR signalling pathway are under the control of female sex steroids. In a previous study, we could already demonstrate the regulation of many members of the AHR battery by 17β-estradiol (E2) in the uterus of rats. In this study, we addressed the potential role of progesterone (P4) in this context. In a comparative approach using ovariectomized rats which were treated for 3 days with either vehicle control, E2, progesterone (P4) or the combination of both hormones in addition to sham-operated animals, we could demonstrate that in addition to E2, P4 is also an important factor in regulating AHR signalling in the rat uterus. P4 has effects similar to E2 on uterine Ahr, Arnt and Arnt2 mRNA levels, resulting in a downregulation of these genes, while the E2-mediated downregulation of key AHR response genes Cyp1a1, Gsta2 and Ugt1 is completely antagonized by P4. As with E2, P4 leads to an increase in uterine AHR levels, especially in the endometrial epithelium despite the decrease in corresponding mRNA levels. This indicates a complex gene-specific regulatory network involving E2, P4 and possibly AHR itself to maintain all components of the AHR signalling cascade at the required levels during all stages of the oestrous cycle and pregnancy.
Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany.
Felicitas
F
Rataj
Frank Josef
FJ
Möller
Maria
M
Jähne
Pia
P
Hönscheid
Oliver
O
Zierau
Günter
G
Vollmer
Georg
G
Kretzschmar
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects*; D007150:Immunohistochemistry; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018336:Receptors, Aryl Hydrocarbon; D011374:Progesterone; D004958:Estradiol