title: Lysosomes are involved in induction of steroidogenic acute regulatory protein (StAR) gene expression and progesterone synthesis through low-density lipoprotein in cultured bovine granulosa cells.
abstract: Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL.
authors.affiliation: Laboratory of Animal Reproductive Science, College of Animal Science and Technology, Northeast Agricultural University, Harbin, China; National Key Laboratory of Animal Nutrition, Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing, China; Animal Husbandry and Veterinary Institute, Heilongjiang Academy of Land Reclamation Sciences, Harbin, China.
authors.forename: Jin-You
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Animal Nutrition, Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: National Key Laboratory of Animal Nutrition, Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Shuan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: National Key Laboratory of Animal Nutrition, Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Animal Nutrition, Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Shen-Ming
authors.initials: SM
authors.lastname: Zeng
authors.affiliation: Laboratory of Animal Reproductive Science, College of Animal Science and Technology, Northeast Agricultural University, Harbin, China. Electronic address: Gxzhang@neau.edu.cn.
authors.forename: Gui-Xue
authors.initials: GX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D008077:Lipoproteins, LDL; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone
keywords: Bovine; Granulosa cell; Low-density lipoprotein; Lysosome; StAR