Gonadotropin-releasing hormone has a biphasic action on aromatase activity through protein kinase C in granulosa cells.
Gonadotropin-releasing hormone (GnRH) exerts direct effects on the ovary by binding to its specific receptor, and stimulates inositol phospholipid turnover in granulosa cells. This study was undertaken to determine the involvement of protein kinase C in the action of GnRH on follicle-stimulating hormone (FSH)-stimulated aromatase activity in rat granulosa cells. The aromatase activity was examined by conversion of exogenously supplied androstenedione to estrogen. FSH stimulated aromatase activity, with a low rate of estrogen production for the first 18 hours, followed by a high rate of production on further incubation. Addition of GnRH potentiated the aromatase response to FSH in the first 18 hours, but caused a dose-dependent inhibition of the FSH-stimulated aromatase activity from 20 to 45 hours of incubation. Half-maximal effects of GnRH occurred at 10 nM. Both of the biphasic actions of GnRH on aromatase response to FSH were mimicked by protein kinase C activators, phobol myristate acetate (PMA) and oleoylacetyl glycerol; maximal effects occurred at 1 to 10 ng/mL. When the cells were exposed first to FSH for 18 hours and then to PMA, the second phase of estrogen production was also suppressed. The second phase, producing quantitative estrogen, might result from induction of the enzyme, because cycloheximide (100 ng/mL) prevented the FSH-induced activation of aromatase from 20 hours of incubation. These results indicate that the biphasic actions of GnRH on FSH-stimulated aromatase activity are mediated by protein kinase C. The inhibitory action of GnRH on quantitative steroidogenesis caused by prolonged FSH stimulation might be expressed through the impaired induction of aromatase.
Imai
A
A
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Iida
K
K
Tamaya
T
T
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D000735:Androstenedione; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate