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Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis

Nakamura, Eri and Otsuka, Fumio and Inagaki, Kenichi and Miyoshi, Tomoko and Tsukamoto, Naoko and Ogura-Ochi, Kanako and Takeda, Masaya and Toma, Kishio and Makino, Hirofumi (2013) Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis. The Journal of steroid biochemistry and molecular biology, 134. pp. 67-74. ISSN 0960-0760

Abstract

Somatostatin is expressed in the hypothalamus, pancreas and gastrointestinal tracts and it inhibits the secretion of various hormones in vivo. In the rodent ovary, somatostatin receptor (SSTR) subtypes 2 and 5 are mainly expressed in granulosa cells and oocytes. Although somatostatin analogs have been clinically used for treatment of endocrine tumors, the direct impact of somatostatin analogs on gonadal functions has yet to be elucidated. In the present study, we investigated the effects of somatostatin analogs (octreotide and pasireotide) on ovarian steroidogenesis by rat primary granulosa cell culture. Treatment with somatostatin analogs decreased FSH-induced estradiol production with reduction in aromatase mRNA expression, while the treatment also suppressed FSH-induced progesterone production with reduction of mRNAs levels of StAR, P450scc and 3βHSD2 in granulosa cells. This trend was also observed in a granulosa/oocyte co-culture condition. The effect of pasireotide was more potent than that of octreotide. FSH-induced synthesis of steroids and cAMP was also suppressed by somatostatin analog treatment. Notably, pretreatment with a BMP-binding protein, noggin, reversed the suppressive effects of somatostatin analogs on progesterone and cAMP production, suggesting that the endogenous BMP system is functionally involved in the SSTR effects in granulosa cells. Treatment with BMP-2, -4, -6 and -7 decreased the mRNA expression of inhibitory Smads6 and 7, leading to enhancement of BMP actions detected by Id-1 transcription in granulosa cells. Collectively, the results revealed that SSTR activity modulates ovarian steroidogenesis by upregulating endogenous BMP activity in growing follicles.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/8119

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