[Effects of gonadotropin-releasing hormone and its analogue (buserelin) on aromatase in cultured human granulosa cells].
We studied the direct effects of gonadotropin-releasing hormone (GnRH) and its analogue (buserelin) on aromatase activity and the aromatase cytochrome P-450 (P-450arom) concentration in cultured human granulosa cells which were obtained during oocyte retrieval for in vitro fertilization. Aromatase activity was assessed by radioassay with [1beta-3H]androstenedione as the substrate. The P-450arom concentration was determined by an enzyme-linked immunosorbent assay with specific antibodies to P-450arom. Buserelin stimulated aromatase activity and P-450arom at low concentrations (10(-13) - 10(-9)M), but it suppressed these parameters at high concentrations (10(-8) - 10(-7)M). The stimulatory effect increased with time during 12- to 48-h culture and disappeared after 72-h culture. Follicle-stimulating hormone (FSH) (100 ng/ml) stimulated aromatase activity and the P-450arom concentration but, FSH stimulation was suppressed by co-administration of low or high concentrations of buserelin. In contrast GnRH suppressed aromatase activity and P-450arom at all concentrations (10(-12) - 10(-6)M). GnRH also suppressed FSH stimulation of aromatase. Aromatase activity was correlated with the P-450arom concentration. These results suggest that in human preovulatory granulosa cells, buserelin and GnRH modulate aromatase activity by changing the P-450arom concentration.
Maeda
K
K
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.
Kitawaki
J
J
Yokota
K
K
Noguchi
T
T
Urabe
M
M
Yamamoto
T
T
Honjo
H
H
D001141:Aromatase / Q000378:metabolism*; D002064:Buserelin / Q000494:pharmacology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans
D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D002064:Buserelin