Granulosa cell aromatase enzyme activity: effects of follicular fluid from patients with polycystic ovary syndrome, using aromatase conversion and [11C]vorozole-binding assays.
The local regulation of ovarian aromatase enzyme in polycystic ovary syndrome (PCOS) was studied with aromatase conversion and [11C]vorozole-binding assays to analyze aromatase activity, substrate-enzyme affinity and number of aromatase binding sites in non-cultured human granulosa cells (GC) incubated with different sources and preparations of follicular fluid (FF). Incubation with FF from women stimulated in in vitro fertilization cycles with follicle-stimulating hormone yielded higher conversion activity than with FF from healthy women and PCOS patients, paralleled with higher substrate affinity (lower Kd) than with FF from healthy women. In PCOS women, charcoal-pretreated FF yielded higher conversion, whereas the ether-pretreated FF yielded lower conversion activity, than with untreated PCOS FF. Both preparations of FF yielded higher affinity to substrate (lower Kd values) and the ether-pretreated FF a lower number of binding sites (Bmax). It seems that steroids with the presence of proteins in PCOS FF reduced aromatase conversion activity through decreased substrate affinity, whereas FF preparations devoid of proteins reduced the aromatase conversion activity mainly through blocking of aromatase active sites. Identification of specific agents responsible for this rapid regulation of aromatase function might help to understand normal regulation of the menstrual cycle and supposed imbalances of inhibitors/activators in PCOS.
Kirilovas
Dmitrijus
D
Department of Women's and Children's Health, Section for Obstetrics and Gynecology, University Hospital, Uppsala, Sweden.
Chaika
Andrey
A
Bergström
Mats
M
Bergström-Petterman
Elizabeth
E
Carlström
Kjell
K
Nosenko
Jelena
J
Korniyenko
Svetlana
S
Yakovets
Anna
A
Mogilevkina
Iryna
I
Naessen
Tord
T
D001141:Aromatase / Q000032:analysis / Q000378:metabolism*; D003947:Diagnostic Techniques, Radioisotope; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry* / Q000201:enzymology; D006107:Granulosa Cells / Q000201:enzymology*; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D013379:Substrate Specificity; D014230:Triazoles / Q000737:chemistry
D004967:Estrogens; D014230:Triazoles; C060523:vorozole; D001141:Aromatase