Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Li, Wei-Ren; Chen, Liang; Chen, Zhijie; Hua, Xing; Liu, Tao; Zhang, Yanquan; Li, Guangyong; Zhou, Feng; Gong, Yanqing; Gao, Zhiqiang; Xin, Zhongcheng

doi:10.1038/aja.2011.85

Cited by 71 publications

(62 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the exact role of autophagy in granulosa/luteal cell function is not clear, autophagy is generally hypothesized to be a critical regulator of cell metabolism and homeostasis (72). With respect to other reproductive tissues, Becn1 has been linked to testosterone production in mouse Leydig cells (73). This data nicely dovetails our findings and suggests that Becn1 has a broader role in steroid production in other organs.…”

Section: Discussionsupporting

confidence: 42%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40-75% of human breast, ovarian, and prostate cancers. Because Becn1 is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becn1 provides essential functions in the ovary that are essential for mammalian reproduction.A utophagy is an evolutionarily conserved cellular process from yeast to mammals that recycles long-lived proteins and organelles to maintain cell energy homeostasis, and is classically activated through the nutrient sensor, mammalian target of rapamycin complex (1-3). Cellular material is encapsulated within a double phospholipid bilayer organelle called the "autophagosome," which fuses with a lysosome to degrade the internalized debris. Using genetic screens in yeast, more than 34 autophagyrelated (Atg) genes have been identified, with most having clear homologs in higher eukaryotes through protein-sequence identity (4-6). BECLIN1 (BECN1), a haploinsufficient tumor suppressor, is an essential autophagy protein that directs the initiation phase and maturation-fusion phase through its participation in two distinct phosphoinositide 3-kinase class III complexes (7-9). Autophagy is not only important for normal development, but it is linked to an array of diseases including neurodegenerative disorders, liver disease, heart disease, inflammatory diseases, and cancer (10, 11). We previously showed a role for BECN1 and autophagy in the establishment of the murine primordial follicle pools in a germ-line knockout model (12). In this study, we follow up on these results and investigate the role of BECN1 in ovarian granulosa cells.In mammals, the success of early pregnancy from embryo implantation to development of the conceptus depends on the function of an ephemeral endocrine gland, the "corpus luteum" (CL), which rapidly forms in the ovary from the remains of the ovulated follicle and migrating somatic cells through a process called "luteinization." Progesterone is an essential hormone that acts at several different levels during pregnancy, including the development of the endometrium for implantation of the embryo and the maintenance of pregnancy through quiescence of the myometrium (13,14). Luteal cells within the CL use cholesterol for steroidogenesis to produce progesterone ...

show abstract

Section: Discussionsupporting

confidence: 42%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In the case of aged Leydig cells, decreased autophagy, particularly mitophagy or the selective degradation of damaged mitochondria, leads to a decrease in the clearance of dysfunctional mitochondria and consequently, an accumulation of ROS. As ROS are detrimental to Leydig cell steroidogenesis (Zirkin & Chen 2000, Diemer et al 2003, this accumulation leads to a decrease in testosterone levels, ultimately resulting in conditions such as late-onset hypogonadism (Li et al 2011).…”

Section: Ovaries and Testesmentioning

confidence: 99%

Autophagy in the endocrine glands

Weckman¹,

Ieva²,

Rotondo³

et al. 2014

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Autophagy is an important cellular process involving the degradation of intracellular components. Its regulation is complex and while there are many methods available, there is currently no single effective way of detecting and monitoring autophagy. It has several cellular functions that are conserved throughout the body, as well as a variety of different physiological roles depending on the context of its occurrence in the body. Autophagy is also involved in the pathology of a wide range of diseases. Within the endocrine system, autophagy has both its traditional conserved functions and specific functions. In the endocrine glands, autophagy plays a critical role in controlling intracellular hormone levels. In peptide-secreting cells of glands such as the pituitary gland, crinophagy, a specific form of autophagy, targets the secretory granules to control the levels of stored hormone. In steroid-secreting cells of glands such as the testes and adrenal gland, autophagy targets the steroid-producing organelles. The dysregulation of autophagy in the endocrine glands leads to several different endocrine diseases such as diabetes and infertility. This review aims to clarify the known roles of autophagy in the physiology of the endocrine system, as well as in various endocrine diseases.

show abstract

“…In Leydig cells, autophagy regulates the accumulation of ROS by promoting the clearance of damaged mitochondria, oxidized cellular substrates, and by activating antioxidant systems. Inhibition of autophagy by disrupting Beclin1 decreases the expression of StAR, while inducing autophagy in Leydig cells from aged or young rat by rapamycin increases the expression of StAR under the stimulation of LH [40]. Thus, it is possible that the downregulation of testosterone in aged Leydig cells might result from two aspects: (1) the deficiency of autophagic machinery and (2) the increase of ROS level.…”

Section: Autophagy and Leydig Cell Functionmentioning

confidence: 99%

“…These evidences lead to the hypothesis that the autophagic activity might relate to the regulation of hormonal secretion in Leydig cells. Indeed, the process of autophagy is high related to the production of testosterone in rat Leydig cells, and the deficiency of autophagy is frequently associated with the dysregulation of testicular homeostasis [40]. However, little is known about the relationship between autophagy and testosterone production in Leydig cells under physiological conditions.…”

Section: Autophagy and Leydig Cell Functionmentioning

confidence: 99%

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

Tang¹,

Wang²

2017

Testes and Ovaries - Functional and Clinical Differences and Similarities

View full text Add to dashboard Cite

Mammalian spermatogenesis is a high regulated biological process occurring in the seminiferous tubules in the testis. The processing of this program requires delicate balance between cell proliferation, differentiation, apoptosis, and expedite cell interaction.Autophagy, an evolutionarily conserved cell reprograming machinery, had been shown to function as an important regulatory mechanism in spermatogenesis and steroid production in testis. Herein, we mainly focused on our understanding of autophagy in mammalian testis. By showing autophagy in physiological and pathophysiological conditions, we try to elicit the regulatory role of autophagy in spermatogenic cells and somatic cells of testis. Moreover, this review is intended to point out factors and mechanisms, which contribute to the initiation of autophagy in testicular cells.

show abstract

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Cited by 71 publications

References 41 publications

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Autophagy in the endocrine glands

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

Contact Info

Product

Resources

About