Interleukin-6 decreases estrogen production and messenger ribonucleic acid expression encoding aromatase during in vitro cytodifferentiation of rat granulosa cell.
To elucidate the influence of interleukin-6 (IL-6) on the maturation of rat granulosa cell (GC), we have established a differentiation model of rat GC in vitro and examined the expression of IL-6 and its receptors, and its possible actions during GC maturation. Bioactive IL-6 was detectable in the conditioned media of GC at approximately 2.5 ng/ml/24 h per 5x10(5) cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that messenger RNAs encoding components of functional IL-6 receptor, namely both ligand-binding subunit (IL-6R) and gp130, were expressed in GC. Treatment of GC with IL-6 for 72 h during the process of in vitro GC maturation dose-dependently inhibited the accumulation of estradiol-17beta (E(2)) and the expression of cytochrome P450 aromatase (P450arom). IL-6 did not change nitric oxide (NO) production and inducible NO synthase expression, implying that IL-6-induced suppression on E(2) levels is dissociated with NO expression. Further, GC which had been incubated with neutralizing anti-IL-6 antibody showed a distinct increase in the levels of P450arom mRNA. These results suggest that IL-6 may attenuate E(2) production partially by inhibiting the expression of aromatase mRNA as an intraovarian regulator for suppressing GC maturation.
Tamura
K
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1, Hachioji-shi, Tokyo 192-0392, Japan. hiro@ps.toyaku.ac.jp
Kawaguchi
T
T
Hara
T
T
Takatoshi
S
S
Tohei
A
A
Miyajima
A
A
Seishi
T
T
Kogo
H
H
D000818:Animals; D001141:Aromatase / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000166:cytology*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000096:biosynthesis
D004967:Estrogens; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011974:Receptors, LH; D009569:Nitric Oxide; D001141:Aromatase