Leptin Receptor Mediates Bmal1 Regulation of Estrogen Synthesis in Granulosa Cells

Overview

Journal Animals (Basel)

Date 2019 Nov 6

PMID 31683864

Citations 8

Authors

Guiyan Chu

Guangjun Ma

Jingchun Sun

Youbo Zhu

Aoqi Xiang

Gongshe Yang

Shiduo Sun

Affiliations

Soon will be listed here.

Abstract

Chronobiology affects female fertility in mammals. Lepr is required for leptin regulation of female reproduction. The presence of E-box elements in the promoter that are recognized and bound by clock genes to initiate gene transcription suggested that circadian systems might regulate fertility through . However, it is unclear whether Bmal1, a key oscillator controlling other clock genes, is involved in leptin regulation in hormone synthesis through Lepr. In this study, serum estradiol (E) concentration and the expressions of , , , and genes were found to display well-synchronized circadian rhythms. Knockdown of significantly reduced expression levels of , , and genes; protein production of Bmal1, Lep, and Cyp19a1; and the E concentration in granulosa cells. Knockdown of reduced the expression levels of and genes and Cyp19a1 protein, and also reduced E concentration. Addition of leptin affected the expression of , , and genes. deficiency counteracted leptin-stimulated upregulation of the genes encoding E synthesis in granulosa cells. These results demonstrated that Bmal1 participates in the process by which leptin acts on to regulate E synthesis.

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References

Shub Y, Ashkenazi I, Reinberg A . Differences between left- and right-hand reaction time rhythms: indications of shifts in strategies of human brain activity. Brain Res Cogn Brain Res. 1998; 6(2):141-6. DOI: 10.1016/s0926-6410(97)00025-6. View

Batista A, Silva D, Rego M, Silva F, Silva E, Beltrao E . The expression and localization of leptin and its receptor in goat ovarian follicles. Anim Reprod Sci. 2013; 141(3-4):142-7. DOI: 10.1016/j.anireprosci.2013.08.007. View

Reinberg A, Nouguier J, GORCEIX A, Mechkouri M, Touitou Y, Ashkenazi I . Circadian rhythm period in reaction time to light signals: difference between right- and left-hand side. Brain Res Cogn Brain Res. 1998; 6(2):135-40. DOI: 10.1016/s0926-6410(97)00024-4. View

Harrath A, Ostrup O, Rafay J, Florkovicova I, Laurincik J, Sirotkin A . Metabolic state defines the response of rabbit ovarian cells to leptin. Reprod Biol. 2016; 17(1):19-24. DOI: 10.1016/j.repbio.2016.11.002. View

Chu A, Zhu L, Blum I, Mai O, Leliavski A, Fahrenkrug J . Global but not gonadotrope-specific disruption of Bmal1 abolishes the luteinizing hormone surge without affecting ovulation. Endocrinology. 2013; 154(8):2924-35. DOI: 10.1210/en.2013-1080. View

Amaral F, Castrucci A, Cipolla-Neto J, Poletini M, Mendez N, Richter H . Environmental control of biological rhythms: effects on development, fertility and metabolism. J Neuroendocrinol. 2014; 26(9):603-12. DOI: 10.1111/jne.12144. View

Finn P, Cunningham M, Pau K, Spies H, Clifton D, Steiner R . The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey. Endocrinology. 1998; 139(11):4652-62. DOI: 10.1210/endo.139.11.6297. View

Yoshii T, Hermann-Luibl C, Helfrich-Forster C . Circadian light-input pathways in Drosophila. Commun Integr Biol. 2016; 9(1):e1102805. PMC: 4802797. DOI: 10.1080/19420889.2015.1102805. View

Hu S, Gan C, Wen R, Xiao Q, Gou H, Liu H . Role of leptin in the regulation of sterol/steroid biosynthesis in goose granulosa cells. Theriogenology. 2014; 82(5):677-85. DOI: 10.1016/j.theriogenology.2014.05.025. View

10.

Wang W, Yin L, Bai L, Ma G, Zhao C, Xiang A . Bmal1 interference impairs hormone synthesis and promotes apoptosis in porcine granulosa cells. Theriogenology. 2017; 99:63-68. DOI: 10.1016/j.theriogenology.2017.05.010. View

11.

Wen R, Hu S, Xiao Q, Han C, Gan C, Gou H . Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway. J Steroid Biochem Mol Biol. 2015; 149:70-9. DOI: 10.1016/j.jsbmb.2015.01.001. View

12.

Elias C, Purohit D . Leptin signaling and circuits in puberty and fertility. Cell Mol Life Sci. 2012; 70(5):841-62. PMC: 3568469. DOI: 10.1007/s00018-012-1095-1. View

13.

De Placido G, Alviggi C, Clarizia R, Mollo A, Alviggi E, Strina I . Intra-follicular leptin concentration as a predictive factor for in vitro oocyte fertilization in assisted reproductive techniques. J Endocrinol Invest. 2006; 29(8):719-26. DOI: 10.1007/BF03344182. View

14.

Beymer M, Henningsen J, Bahougne T, Simonneaux V . The role of kisspeptin and RFRP in the circadian control of female reproduction. Mol Cell Endocrinol. 2016; 438:89-99. DOI: 10.1016/j.mce.2016.06.026. View

15.

Mereness A, Murphy Z, Forrestel A, Butler S, Ko C, Richards J . Conditional Deletion of Bmal1 in Ovarian Theca Cells Disrupts Ovulation in Female Mice. Endocrinology. 2015; 157(2):913-27. PMC: 5393362. DOI: 10.1210/en.2015-1645. View

16.

Dupuis L, Schuermann Y, Cohen T, Siddappa D, Kalaiselvanraja A, Pansera M . Role of leptin receptors in granulosa cells during ovulation. Reproduction. 2013; 147(2):221-9. DOI: 10.1530/REP-13-0356. View

17.

Mounzih K, Lu R, Chehab F . Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology. 1997; 138(3):1190-3. DOI: 10.1210/endo.138.3.5024. View

18.

Sen A, Sellix M . The Circadian Timing System and Environmental Circadian Disruption: From Follicles to Fertility. Endocrinology. 2016; 157(9):3366-73. DOI: 10.1210/en.2016-1450. View

19.

Friedman J . The function of leptin in nutrition, weight, and physiology. Nutr Rev. 2002; 60(10 Pt 2):S1-14; discussion S68-84, 85-7. DOI: 10.1301/002966402320634878. View

20.

Liu Y, Johnson B, Shen A, Wallisser J, Krentz K, Moran S . Loss of BMAL1 in ovarian steroidogenic cells results in implantation failure in female mice. Proc Natl Acad Sci U S A. 2014; 111(39):14295-300. PMC: 4191810. DOI: 10.1073/pnas.1209249111. View