Abstract
The ovarian bone morphogenetic protein (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 by suppressing adenylate cyclase activity. In the present study, we studied the role of melatonin in ovarian steroidogenesis using rat primary granulosa cells of immature female rat ovaries by focusing on the interaction with BMP-6 activity. 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 elucidate the interaction between activities of melatonin and BMPs, the effect of melatonin treatment on suppression of progesterone synthesis by BMP-6 was investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by co-treatment with melatonin. Granulosa cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8 phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting that melatonin has an inhibitory effect on BMP receptor signaling in granulosa cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not affected by melatonin, inhibitory Smad6, but not Smad7, expression was upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary. These findings suggest that the effect of melatonin on maintenance of ovarian function is, at least in part, due to the regulation of endogenous BMP activity in granulosa cells.
| Original language | English |
|---|---|
| Pages (from-to) | 233-239 |
| Number of pages | 7 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 143 |
| DOIs | |
| Publication status | Published - 2014 |
Fingerprint
Keywords
- Bone morphogenetic protein (BMP)
- Follicle-stimulating hormone (FSH)
- Granulosa cells
- Melatonin
- Oocyte
- Steroidogenesis
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Endocrinology
- Cell Biology
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
- Molecular Medicine
Cite this
Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells. / Nakamura, Eri; Otsuka, Fumio; Terasaka, Tomohiro; Inagaki, Kenichi; Hosoya, Takeshi; Tsukamoto-Yamauchi, Naoko; Toma, Kishio; Makino, Hirofumi.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 143, 2014, p. 233-239.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melatonin counteracts BMP-6 regulation of steroidogenesis by rat granulosa cells
AU - Nakamura, Eri
AU - Otsuka, Fumio
AU - Terasaka, Tomohiro
AU - Inagaki, Kenichi
AU - Hosoya, Takeshi
AU - Tsukamoto-Yamauchi, Naoko
AU - Toma, Kishio
AU - Makino, Hirofumi
PY - 2014
Y1 - 2014
N2 - The ovarian bone morphogenetic protein (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 by suppressing adenylate cyclase activity. In the present study, we studied the role of melatonin in ovarian steroidogenesis using rat primary granulosa cells of immature female rat ovaries by focusing on the interaction with BMP-6 activity. 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 elucidate the interaction between activities of melatonin and BMPs, the effect of melatonin treatment on suppression of progesterone synthesis by BMP-6 was investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by co-treatment with melatonin. Granulosa cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8 phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting that melatonin has an inhibitory effect on BMP receptor signaling in granulosa cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not affected by melatonin, inhibitory Smad6, but not Smad7, expression was upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary. These findings suggest that the effect of melatonin on maintenance of ovarian function is, at least in part, due to the regulation of endogenous BMP activity in granulosa cells.
AB - The ovarian bone morphogenetic protein (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 by suppressing adenylate cyclase activity. In the present study, we studied the role of melatonin in ovarian steroidogenesis using rat primary granulosa cells of immature female rat ovaries by focusing on the interaction with BMP-6 activity. 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 elucidate the interaction between activities of melatonin and BMPs, the effect of melatonin treatment on suppression of progesterone synthesis by BMP-6 was investigated. Interestingly, the inhibitory effect of BMP-6 on FSH-induced progesterone production was impaired by co-treatment with melatonin. Granulosa cells express higher levels of MT1 than MT2, and BMP-6 had no significant effect on MT1 expression in granulosa cells. However, BMP-6-induced Smad1/5/8 phosphorylation and Id-1 transcription were suppressed by melatonin, suggesting that melatonin has an inhibitory effect on BMP receptor signaling in granulosa cells. Although the expression levels of ALK-2, -6, ActRII and BMPRII were not affected by melatonin, inhibitory Smad6, but not Smad7, expression was upregulated by melatonin. Thus, melatonin plays a role in the regulation of BMP-6 signal intensity for controlling progesterone production in the ovary. These findings suggest that the effect of melatonin on maintenance of ovarian function is, at least in part, due to the regulation of endogenous BMP activity in granulosa cells.
KW - Bone morphogenetic protein (BMP)
KW - Follicle-stimulating hormone (FSH)
KW - Granulosa cells
KW - Melatonin
KW - Oocyte
KW - Steroidogenesis
UR - http://www.scopus.com/inward/record.url?scp=84899789246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899789246&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2014.04.003
DO - 10.1016/j.jsbmb.2014.04.003
M3 - Article
C2 - 24751708
AN - SCOPUS:84899789246
VL - 143
SP - 233
EP - 239
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
ER -