Characterization of [11C]vorozole binding in ovarian tissue in rats throughout estrous cycle in association with conversion of androgens to estrogens in vivo and in vitro.
Estrogen levels vary in a cyclic fashion during the rat estrous cycle, reaching peak concentrations during proestrus. Previously, it was suggested that the preovulatory peak in estrogen production in rats in vivo is regulated by other control mechanisms than concentration of precursor and amount of aromatase enzyme, changing the specific activity of the enzyme. To explore this hypothesis, ovarian binding of [11C]vorozole in vivo and in vitro, representing the amount of active aromatase, and conversion activity of ovarian homogenate were assayed together with serum androstenedione (A4) and estradiol-17beta (E2) levels during the estrous cycle in rats. The reducing ovarian [11C]vorozole binding in vivo from proestrus +4 up to +8h might indicate that the ovarian aromatase is blocked, probably to prevent premature increase of E2 levels. Thereafter (between proestrus +9 and +13h), the binding dramatically increases (aromatase enzyme is unblocked), to enable increased E2 synthesis. In addition, during the latter period, serum E2 levels were strongly correlated with serum A4 levels after adjustment for amount of ovarian aromatase (P=0.03), but not with amount of aromatase adjusted for levels of A4 (P=0.13), which might indicate changes in specific activity of the aromatase enzyme. Significant correlation between Kd and serum E2 levels during the same period indicated that aromatase-precursor affinity might be involved in the regulation of the enzyme-specific activity. This conclusion is done assuming that [11C]vorozole binding mimics that of the substrate (A4). The [11C]vorozole in vivo technique keeps auto- and paracrine mechanisms intact, and might therefore yield additional information about biological processes compared with traditional in vitro techniques.
Kirilovas
Dmitrijus
D
Department of Women's and Children's Health, Section for Obstetrics and Gynecology, University Hospital, SE-751 85 Uppsala, Sweden.
Naessen
Tord
T
Bergström
Mats
M
Bergström-Petterman
Elizabeth
E
Carlström
Kjell
K
Långström
Bengt
B
D000735:Androstenedione / Q000097:blood*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004958:Estradiol / Q000097:blood*; D030762:Estrous Cycle / Q000502:physiology*; D004971:Estrus / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000378:metabolism*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D014230:Triazoles; C060523:vorozole; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D001141:Aromatase