Interaction of melatonin and BMP-6 in regulation of steroidogenesis by rat granulosa cells

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 358-380-Steroid Hormone Biosynthesis & Metabolism
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-365
Eri Nakamura*1, Fumio Otsuka2, Kenichi Inagaki1, Tomoko Miyoshi2, Naoko Tsukamoto1, Kishio Toma1, Tomohiro Terasaka2 and Hirofumi Makino2
1Okayama University Hospital, Okayama, Japan, 2Okayama Univ Grad School, Okayama, Japan
Ovarian follicle growth and maturation occur as a result of complex interactions between pituitary gonadotropins and autocrine/paracrine factors expressed in the ovary.  Melatonin is functionally involved in the regulation of circadian rhythm and the activities of hormone and cytokine.  It has been revealed that melatonin modulates the ovarian function by regulating gonadotropin release in the hypothalamus-pituitary gland axis.  Melatonin receptors including MT1 and MT2 were detected in various endocrine tissues including GnRH neurons and ovaries, suggesting that melatonin plays a functional role in the reproductive system not only centrally but also peripherally in the ovary.  On the other hand, recent studies have also shown that BMPs play important roles as autocrine/paracrine factors in female fertility in mammals.  The regulation of FSH responsiveness in growing follicles is important for the establishment of dominant follicles and subsequent ovulation.  The ovarian BMP system is a physiological inhibitor of luteinization in growing ovarian follicles.  BMP-6, which is expressed in oocytes and granulosa cells of healthy follicles, specifically inhibits FSH actions and cAMP synthesis by suppressing adenylate cyclase activity.  In the present study, we studied the role of melatonin in ovarian steroidogenesis regulated by BMP-6 using rat primary granulosa cells of immature female rat ovaries.  Treatment with melatonin had no direct effect on FSH-induced progesterone or estradiol production by granulosa cells, and the results were not affected by the presence of co-cultured oocytes.  In addition, synthesis of cAMP by granulosa cells was not significantly altered by melatonin treatment.  To know the interaction between the activities of melatonin and BMPs, the impact of melatonin treatment on BMP-6 suppression of progesterone synthesis was studied.  Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by the co-treatment with melatonin.  Granulosa cells mainly expressed MT1 compared with MT2, in which BMP-6 had no significant effect on the MT1 expression.  However, BMP-6-induced Id-1 transcription was suppressed by melatonin treatment in the presence of FSH, suggesting that melatonin has an inhibitory role on BMP-Smad pathway in granulosa cells.  Thus, it was shown that melatonin plays a key role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary.

Nothing to Disclose: EN, FO, KI, TM, NT, KT, TT, HM

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