Characterization of [ [formula omitted]]vorozole binding in ovarian tissue in rats throughout estrous cycle in association with conversion of androgens to estrogens in vivo and in vitro

• Published in: Steroids 2003, Vol.68 (14), p.1139-1146
• Main Authors: Kirilovas, Dmitrijus, Naessen, Tord, Bergström, Mats, Bergström-Petterman, Elizabeth, Carlström, Kjell, Långström, Bengt
• Format: Article
• Language: English
• Subjects: Androstenedione - blood; Animals; Aromatase; Aromatase - metabolism; Aromatase Inhibitors; Binding Sites; Biological and medical sciences; Enzyme Inhibitors - metabolism; Estradiol - blood; Estrous cycle; Estrous Cycle - physiology; Estrus - metabolism; Female; Fundamental and applied biological sciences. Psychology; In Vitro; In Vitro Techniques; Luteinizing Hormone - blood; Medicin och hälsovetenskap; Ovary; Ovary - metabolism; Positron emission tomography; Radioimmunoassay; Rat; Rats; Rats, Sprague-Dawley; Triazoles - metabolism; Vertebrates: endocrinology; Vorozole
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2003.08.013

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 [ 11 C ]vorozole in vivo and in vitro, representing the amount of active aromatase, and conversion activity of ovarian homogenate were assayed together with serum androstenedione (A 4) and estradiol-17β (E 2) levels during the estrous cycle in rats. The reducing ovarian [ 11 C ]vorozole binding in vivo from proestrus +4 up to +8 h might indicate that the ovarian aromatase is blocked, probably to prevent premature increase of E 2 levels. Thereafter (between proestrus +9 and +13 h), the binding dramatically increases (aromatase enzyme is unblocked), to enable increased E 2 synthesis. In addition, during the latter period, serum E 2 levels were strongly correlated with serum A 4 levels after adjustment for amount of ovarian aromatase ( P=0.03), but not with amount of aromatase adjusted for levels of A 4 ( P=0.13), which might indicate changes in specific activity of the aromatase enzyme. Significant correlation between K d and serum E 2 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 [ 11 C ]vorozole binding mimics that of the substrate (A 4). The [ 11 C ]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.