Hypoxia Promotes Progesterone Synthesis During Luteinization in Bovine Granulosa Cells |
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Authors: | FADHILLAH Shin YOSHIOKA Ryo NISHIMURA Kiyoshi OKUDA |
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Institution: | 1)Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan;2)Laboratory of Reproductive Physiology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan;3)Laboratory of Theriogenology, Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8550, Japan |
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Abstract: | To determine whether hypoxia has an effect on luteinization, we examined the influence of hypoxia on a model of bovine
luteinizing and non-luteinizing granulosa cell culture. The granulosa cells were obtained from small antral follicles (≤ 6 mm
in diameter). To induce luteinization, the cells were treated for 24 h with insulin (2 µg/ml), forskolin (10 µM) or insulin
in combination with forskolin at 20% O2. After 24 h, progesterone (P4) production was higher in the treated cells,
which we defined as luteinizing granulosa cells, than in non-treated cells, which we defined as non-luteinizing granulosa
cells. P4 production by non-luteinizing granulosa cells was not affected by hypoxia (24 h at 10% and 5% O2), while
P4 production by granulosa cells treated with insulin in combination with forskolin was significantly increased under hypoxia
(24 h at 10% and 5% O2). Because hypoxia affected P4 production by the luteinizing granulosa cells but not by the
non-luteinizing granulosa cells, hypoxia seems to promote P4 production during, rather than before, luteinization. In the
cells treated with insulin in combination with forskolin, mRNA and protein expression of steroidogenic acute regulatory
protein (StAR) and protein expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) increased under 10% O2, while
mRNA and protein expressions of key protein and enzymes in P4 biosynthesis did not increase under 5% O2. The
overall results suggest that hypoxia plays a role in progressing and completing the luteinization by enhancing P4 production
through StAR as well as 3β-HSD expressions in the early time of establishing the corpus luteum. |
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Keywords: | Granulosa cells Hypoxia Luteinization Progesterone |
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