Androgen and Luteinizing Hormone Stimulate the Function of Rat Immature Leydig Cells Through Different Transcription Signals

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 Apr 5

PMID 33815270

Citations 5

Authors

Xiaoheng Li

Qiqi Zhu

Zina Wen

Kaimin Yuan

Zhijian Su

Yiyan Wang

Ying Zhong

Ren-Shan Ge

Affiliations

Soon will be listed here.

Abstract

The function of immature Leydig cells is regulated by hormones, such as androgen and luteinizing hormone (LH). However, the regulation of this process is still unclear. The objective of this study was to determine whether luteinizing hormone (LH) or androgens contribute to this process. Immature Leydig cells were purified from 35-day-old male Sprague Dawley rats and cultured with LH (1 ng/ml) or androgen (7α-methyl-19- nortestosterone, MENT, 100 nM) for 2 days. LH or MENT treatment significantly increased the androgens produced by immature Leydig cells in rats. Microarray and qPCR and enzymatic tests showed that LH up-regulated the expression of , , , and while down-regulated the expression of and . On the contrary, the expression of was up-regulated by MENT. LH and MENT regulate Leydig cell function through different sets of transcription factors. We conclude that LH and androgens participate in the regulation of rat immature Leydig cell function through different transcriptional pathways.

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References

Ge R, Hardy M . Variation in the end products of androgen biosynthesis and metabolism during postnatal differentiation of rat Leydig cells. Endocrinology. 1998; 139(9):3787-95. DOI: 10.1210/endo.139.9.6183. View

Griffin D, Ellis P, Dunmore B, Bauer J, Abel M, Affara N . Transcriptional profiling of luteinizing hormone receptor-deficient mice before and after testosterone treatment provides insight into the hormonal control of postnatal testicular development and Leydig cell differentiation. Biol Reprod. 2010; 82(6):1139-50. PMC: 2874499. DOI: 10.1095/biolreprod.109.082099. View

Shan L, Phillips D, Bardin C, Hardy M . Differential regulation of steroidogenic enzymes during differentiation optimizes testosterone production by adult rat Leydig cells. Endocrinology. 1993; 133(5):2277-83. DOI: 10.1210/endo.133.5.8404681. View

Yoshino M, Mizutani T, Yamada K, Tsuchiya M, Minegishi T, Yazawa T . Early growth response gene-1 regulates the expression of the rat luteinizing hormone receptor gene. Biol Reprod. 2002; 66(6):1813-9. DOI: 10.1095/biolreprod66.6.1813. View

Odeh H, Kleinguetl C, Ge R, Zirkin B, Chen H . Regulation of the proliferation and differentiation of Leydig stem cells in the adult testis. Biol Reprod. 2014; 90(6):123. PMC: 4094000. DOI: 10.1095/biolreprod.114.117473. View

Jo M, Curry Jr T . Luteinizing hormone-induced RUNX1 regulates the expression of genes in granulosa cells of rat periovulatory follicles. Mol Endocrinol. 2006; 20(9):2156-72. PMC: 1783681. DOI: 10.1210/me.2005-0512. View

Murphy L, Jeffcoate I, OShaughnessy P . Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse. Endocrinology. 1994; 135(4):1372-7. DOI: 10.1210/endo.135.4.7925099. View

Hoeffler J, Meyer T, Yun Y, Jameson J, Habener J . Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988; 242(4884):1430-3. DOI: 10.1126/science.2974179. View

Chen P, Zirkin B, Chen H . Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications. Endocr Rev. 2019; 41(1). PMC: 7753054. DOI: 10.1210/endrev/bnz013. View

10.

Ge R, Dong Q, Sottas C, Papadopoulos V, Zirkin B, Hardy M . In search of rat stem Leydig cells: identification, isolation, and lineage-specific development. Proc Natl Acad Sci U S A. 2006; 103(8):2719-24. PMC: 1413776. DOI: 10.1073/pnas.0507692103. View

11.

Strober W . Trypan Blue Exclusion Test of Cell Viability. Curr Protoc Immunol. 2015; 111:A3.B.1-A3.B.3. PMC: 6716531. DOI: 10.1002/0471142735.ima03bs111. View

12.

Habberfield A, Dix C, COOKE B . Effects of lutropin (LH) receptor internalization and recycling on the apparent numbers of LH receptors in rat testis Leydig cells at different temperatures. Mol Cell Endocrinol. 1987; 51(1-2):153-61. DOI: 10.1016/0303-7207(87)90129-8. View

13.

Stanley E, Lin C, Jin S, Liu J, Sottas C, Ge R . Identification, proliferation, and differentiation of adult Leydig stem cells. Endocrinology. 2012; 153(10):5002-10. PMC: 3512003. DOI: 10.1210/en.2012-1417. View

14.

Foulkes N, Mellstrom B, Benusiglio E, Sassone-Corsi P . Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature. 1992; 355(6355):80-4. DOI: 10.1038/355080a0. View

15.

Hardy M, Kelce W, Klinefelter G, EWING L . Differentiation of Leydig cell precursors in vitro: a role for androgen. Endocrinology. 1990; 127(1):488-90. DOI: 10.1210/endo-127-1-488. View

16.

Ye L, Li X, Li L, Chen H, Ge R . Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells. Front Physiol. 2017; 8:430. PMC: 5487449. DOI: 10.3389/fphys.2017.00430. View

17.

Shan L, Hardy D, Catterall J, Hardy M . Effects of luteinizing hormone (LH) and androgen on steady state levels of messenger ribonucleic acid for LH receptors, androgen receptors, and steroidogenic enzymes in rat Leydig cell progenitors in vivo. Endocrinology. 1995; 136(4):1686-93. DOI: 10.1210/endo.136.4.7895679. View

18.

Habberfield A, Dix C, COOKE B . The dynamics of LH-induced desensitization of adenylate cyclase and LH receptor internalization in rat Leydig cells at physiological levels of LH. J Endocrinol. 1987; 114(3):415-22. DOI: 10.1677/joe.0.1140415. View

19.

Tourtellotte W, Nagarajan R, Bartke A, Milbrandt J . Functional compensation by Egr4 in Egr1-dependent luteinizing hormone regulation and Leydig cell steroidogenesis. Mol Cell Biol. 2000; 20(14):5261-8. PMC: 85975. DOI: 10.1128/MCB.20.14.5261-5268.2000. View

20.

Rehfuss R, Walton K, Loriaux M, Goodman R . The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. J Biol Chem. 1991; 266(28):18431-4. View