The expression of CKLFSF2B is regulated by GATA1 and CREB in the Leydig cells, which modulates testicular steroidogenesis

Kumar, Sudeep; Kang, Hana; Park, Eunsook; Park, Hee-Sae; Lee, Keesook

doi:10.1016/j.bbagrm.2018.10.002

Cited by 17 publications

(11 citation statements)

References 57 publications

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“…The constant level of Jagged1 during Leydig cell differentiation and maturation at around 3-5 weeks could be linked to the proper balance of steroidogenic gene expression during testicular development and maturation. Similar repressive effects of CKLFSF2A and CKLFSF2B on testicular steroidogenesis have been previously reported [36,37]. Therefore, the differential expression pattern of Jagged1 and Notch1 in testicular Leydig cells suggests a role of Jagged1 independent of Notch1.…”

Section: Plos Onesupporting

confidence: 84%

Jagged1 intracellular domain modulates steroidogenesis in testicular Leydig cells

2020

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Leydig cells represent the steroidogenic lineage of mammalian testis, which produces testosterone. Genetic evidence indicates the requirement of Notch signaling in maintaining a balance between differentiated Leydig cells and their progenitors during fetal development. In primary Leydig cells, Notch1 expression decreases with testicular development, while the expression of its ligand, Jagged1, remains relatively unchanged, suggesting that the roles of Jagged1 extend beyond Notch signaling. In addition, Jagged1 is known to be processed into its intracellular domain, which then translocate to the nucleus. In this study, we investigated the effect of Jagged1 intracellular domain (JICD) on steroidogenesis in Leydig cells. The independent overexpression of JICD in MA-10 Leydig cells was found to inhibit the activity of cAMP-induced Nur77 promoter. In addition, JICD suppressed Nur77 transactivation of the promoter of steroidogenic genes such as P450scc, P450c17, StAR, and 3β-HSD. Further, adenovirus-mediated overexpression of JICD in primary Leydig cells repressed the expression of steroidogenic genes, consequently lowering testosterone production. These results collectively suggest that steroidogenesis in testicular Leydig cells, which is regulated by LH/cAMP signaling, is fine-tuned by Jagged1 during testis development.

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Section: Plos Onesupporting

confidence: 84%

Jagged1 intracellular domain modulates steroidogenesis in testicular Leydig cells

2020

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“…Moreover, CREB factors cooperate with SF1 (NR5A1, Ad4BP) to enhance Star transcription ( 15 ). CREB also stimulates CKLFSF2B promoter activity in response to LH/cAMP ( 16 ). Cklfsf2b codes for a protein that inhibits steroidogenesis in Leydig cells ( 16 ).…”

Section: Superclass Of Basic Domainsmentioning

confidence: 99%

Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

2022

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Cell differentiation and acquisition of specialized functions are inherent steps in events that lead to normal tissue development and function. These processes require accurate temporal, tissue, and cell-specific activation or repression of gene transcription. This is achieved by complex interactions between transcription factors that form a unique combinatorial code in each specialized cell type and in response to different physiological signals. Transcription factors typically act by binding to short, nucleotide-specific DNA sequences located in the promoter region of target genes. In males, Leydig cells play a crucial role in sex differentiation, health, and reproductive function from embryonic life to adulthood. To better understand the molecular mechanisms regulating Leydig cell differentiation and function, several transcription factors important to Leydig cells have been identified, including some previously unknown to this specialized cell type. This mini review summarizes the current knowledge on transcription factors in fetal and adult Leydig cells, describing their roles and mechanisms of action.

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“…E2 downregulated genes included the immune regulators GZMA and LECT2 [ 42 , 43 , 44 , 45 ]. The most upregulated gene by soy was SMAD6, which is an inhibitor of BMPs and TGF-b signaling, and in vitro experiments showed that SMAD6 overexpression blocks BMPs-induced osteoblast and chondrocyte differentiation [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study

et al. 2022

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Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 group compared to the Milk group related to endocrine/metabolic disorders. However, little overlap was observed between the other treatment groups. These data suggest soy formula is not estrogenic in the male neonatal piglet and that soy formula does not significantly alter male reproductive development.

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The expression of CKLFSF2B is regulated by GATA1 and CREB in the Leydig cells, which modulates testicular steroidogenesis

Cited by 17 publications

References 57 publications

Jagged1 intracellular domain modulates steroidogenesis in testicular Leydig cells

Jagged1 intracellular domain modulates steroidogenesis in testicular Leydig cells

Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study

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