TGF-β1 Regulation of Estrogen Production in Mature Rat Leydig Cells

Abstract

BackgroundBesides androgens, estrogens produced in Leydig cells are also crucial for mammalian germ cell differentiation. Transforming growth factor-β1 (TGF-β1) is now known to have multiple effects on regulation of Leydig cell function. The objective of the present study is to determine whether TGF-β1 regulates estradiol (E2) synthesis in adult rat Leydig cells and then to assess the impact of TGF-β1 on Cx43-based gap junctional intercellular communication (GJIC) between Leydig cells.Methodology/Principal FindingsPrimary cultured Leydig cells were incubated in the presence of recombinant TGF-β1 and the production of E2 as well as testosterone (T) were measured by RIA. The activity of P450arom was addressed by the tritiated water release assay and the expression of Cyp19 gene was evaluated by Western blotting and real time RT-PCR. The expression of Cx43 and GJIC were investigated with immunofluorescence and fluorescence recovery after photo-bleaching (FRAP), respectively. Results from this study show that TGF-β1 down-regulates the level of E2 secretion and the activity of P450arom in a dose-dependent manner in adult Leydig cells. In addition, the expression of Cx43 and GJIC was closely related to the regulation of E2 and TGF-β1, and E2 treatment in turn restored the inhibition of TGF-β1 on GJIC.ConclusionsOur results indicate, for the first time in adult rat Leydig cells, that TGF-β1 suppresses P450arom activity, as well as the expression of the Cyp19 gene, and that depression of E2 secretion leads to down-regulation of Cx43-based GJIC between Leydig cells.

Androgen receptor activation integrates complex transcriptional effects in osteoblasts, involving the growth factors TGF-β and IGF-I, and transcription factor C/EBPδ

“…Even so, TGF-β1 has been shown to increase androgen precursor synthesis from dehydroepiandrosterone as well as the expression of at least three hydroxysteroid dehydrogenases involved in androgen biosynthesis in prostate stromal cells (Piao et al, 2013), predicting its ability to enhance local androgen synthesis within prostate tumors. TGF-β can also decrease aromatase activity in Leydig cells, thus allowing more local DHT accumulation in the absence of testosterone metabolism to 17β-E (Liu et al, 2013). Other recent studies revealed that TGF-β can activate AR in the absence of DHT and, as we show here in osteoblasts, it can cooperate with and enhance AR activation in response to DHT (Yang et al, 2014).…”

Epigallocatechin gallate improves airway inflammation through TGF‑β1 signaling pathway in asthmatic mice

“…Transforming growth factor (TGF)-β has a wide range of biological activities, participates in early embryonic development ( 9 ), cartilage and bone formation, inflammation, interstitial fibrosis, and regulation of immune and endocrine functions ( 10 , 11 ), and tumor formation and development ( 12 , 13 ). Eosinophils and bronchial epithelial cells are the major sources of TGF-β production in the bronchial asthma airway.…”

Modulatory Effects of Estradiol and Its Mixtures with Ligands of GPER and PPAR on MAPK and PI3K/Akt Signaling Pathways and Tumorigenic Factors in Mouse Testis Explants and Mouse Tumor Leydig Cells

“…Administration of PPARγ agonists (as therapeutic treatment in bronchopulmonary dysplasia) inhibits the canonical WNT/TGF-β pathway and stimulates PPARγ activity [ 72 ]. TGF-β1 as PPARγ, suppresses aromatase activity and the expression of the Cyp19 gene as revealed in adult rat Leydig cells [ 73 ]. According to Gonzales et al [ 74 ] TGF-β1 together with progesterone is involved in the hyperplasia and/or hypertrophy of Leydig cells via Smad1/5 signaling.…”