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Regulation of Sertoli cell differentiation by the testicular paracrine factor PModS: potential role of
1Reproductive Endocrinology Center, University of California, San Francisco 94143-0556.
Abstract:
Testicular peritubular cells produce a paracrine factor, PModS, under androgen control that modulates Sertoli cell functions that are essential for the process of spermatogenesis. PModS has a more dramatic effect on Sertoli cell differentiated functions in vitro than any regulatory agent previously shown to influence the cell, including FSH. Investigation of the actions of PModS on a molecular level have used transferrin expression as a marker of Sertoli cell differentiation. PModS was found to stimulate transferrin gene expression while having no effect on transferrin mRNA stability. The ability of PModS to elevate transferrin mRNA levels was inhibited by cycloheximide. Therefore, the actions of PModS require ongoing protein synthesis and appear to be indirectly mediated through trans-acting early event genes. PModS was found to dramatically increase mRNA levels for c-fos, but had no effect on c-jun mRNA levels. The c-fos mRNA levels increased transiently within a few minutes to a maximal level of stimulation at 1 h and returned to basal levels within 6 h. The rise in c-fos mRNA preceded the elevation in transferrin mRNA, which started to increase at 2 h to a maximum level between 6-12 h that was maintained at high levels for several days in cell culture. Treatment of Sertoli cells with an antisense c-fos oligonucleotide was found to inhibit the actions of PModS on transferrin expression. Combined results support the hypothesis that PModS acts indirectly through transcription factors (e.g. c-fos) to induce Sertoli cell differentiated functions (e.g. transferrin expression). Therefore, PModS appears to act as a differentiation-type factor to promote and maintain optimal Sertoli cell function.
Insights
Testicular peritubular cells secrete PModS, a factor that enhances Sertoli cell function and spermatogenesis. This process involves c-fos gene activation and protein synthesis, promoting transferrin expression.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cell Signaling
Background:
- Spermatogenesis relies on Sertoli cell function, which is modulated by paracrine factors.
- Testicular peritubular cells produce PModS, a key regulator of Sertoli cell differentiation under androgen control.
- PModS exhibits a potent effect on Sertoli cell differentiated functions, exceeding that of FSH.
Purpose of the Study:
- To elucidate the molecular mechanisms by which PModS influences Sertoli cell differentiation.
- To identify the role of gene expression and protein synthesis in PModS-mediated effects.
- To investigate the involvement of transcription factors, such as c-fos, in PModS signaling.
Main Methods:
- Sertoli cells were treated with PModS in vitro.
- Transferrin gene expression and mRNA levels were measured as markers of differentiation.
- The effect of cycloheximide and antisense c-fos oligonucleotides on PModS action was assessed.
- mRNA levels for c-fos and c-jun were quantified over time.
Main Results:
- PModS significantly stimulated transferrin gene expression without affecting mRNA stability.
- PModS-induced transferrin mRNA elevation required ongoing protein synthesis.
- PModS rapidly and transiently increased c-fos mRNA levels, preceding transferrin mRNA increase.
- Antisense c-fos oligonucleotide treatment blocked PModS-induced transferrin expression.
Conclusions:
- PModS acts indirectly via transcription factors, notably c-fos, to regulate Sertoli cell differentiation.
- The PModS signaling pathway involves early gene activation and protein synthesis.
- PModS functions as a differentiation-promoting factor essential for optimal Sertoli cell function and spermatogenesis.