Endocrinology, Vol 124, 2711-2719, Copyright © 1989 by Endocrine Society

ARTICLES

Regulation of Sertoli cell function and differentiation through the actions of a testicular paracrine factor P-Mod-S

JN Norton and MK Skinner
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

The current study was designed to investigate the actions of the testicular paracrine factor P-Mod-S on Sertoli cell function and differentiation. Transferrin production by Sertoli cells was stimulated by P-Mod-S to a greater extent than any individual regulatory agent and in a manner similar to a combination of FSH, insulin, retinol, and testosterone (FIRT). P-Mod-S had an additive response in combination with FIRT. The increase in transferrin production with a combination of P-Mod-S and FIRT is the highest level of stimulation (up to 8-fold) observed. These profound effects of P-Mod-S on Sertoli cell function implied a potential unique mechanism of action for the paracrine factor. FSH and FIRT significantly stimulated cAMP levels with both 60- min and 72-h treatments. In contrast, P-Mod-S had no effect on cAMP levels with a 60-min treatment and only a small increase with a 72-h treatment. Interestingly, P-Mod-S stimulated cGMP levels that remained above basal levels up to 72 h of treatment. FSH had no effect on cGMP levels. P-Mod-S did not affect inositol phosphate hydrolysis with treatments between 15 and 60 min. The actions of P-Mod-S on cGMP levels influenced Sertoli cell function on a molecular level. Northern blot analysis indicated that P-Mod-S and FIRT both stimulated the apparent levels of the 2.6-kilobase transcript of transferrin and the 1.7- kilobase transcript of androgen-binding protein. A solution hybridization procedure was used to quantitate the influence of P-Mod-S on Sertoli cell gene expression. P-Mod-S stimulated steady state levels of both transferrin and androgen-binding protein message approximately 2-fold, similar to the effects of FIRT. Both forms of P-Mod-S had similar biological activities and mechanisms of action. P-Mod-S (A) and P-Mod-S (B) both stimulated cGMP, altered Sertoli cell gene expression, and had profound effects on transferrin production. Although slightly different biochemically, both forms of P-Mod-S appear to be functionally similar. Combined observations indicate that the paracrine factor produced by peritubular cells, P-Mod-S, acts on Sertoli cells in part through a cGMP-mediated response to influence the expression of specific genes which subsequently have profound effects on Sertoli cell function and differentiation.

This article has been cited by other articles:

				C. Zhang, S. Yeh, Y.-T. Chen, C.-C. Wu, K.-H. Chuang, H.-Y. Lin, R.-S. Wang, Y.-J. Chang, C. Mendis-Handagama, L. Hu, et al. Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells PNAS, November 21, 2006; 103(47): 17718 - 17723. [Abstract] [Full Text] [PDF]

				C. Chang, Y.-T. Chen, S.-D. Yeh, Q. Xu, R.-S. Wang, F. Guillou, H. Lardy, and S. Yeh Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells PNAS, May 4, 2004; 101(18): 6876 - 6881. [Abstract] [Full Text] [PDF]

				S. Migrenne, C. Racine, F. Guillou, and R. Habert Pituitary Hormones Inhibit the Function and Differentiation of Fetal Sertoli Cells Endocrinology, June 1, 2003; 144(6): 2617 - 2622. [Abstract] [Full Text] [PDF]

				R. Middendorff, M. Kumm, M. S. Davidoff, A. F. Holstein, and D. Müller Generation of Cyclic Guanosine Monophosphate by Heme Oxygenases in the Human Testis--A Regulatory Role for Carbon Monoxide in Sertoli Cells? Biol Reprod, August 1, 2000; 63(2): 651 - 657. [Abstract] [Full Text]

				J. Chaudhary and M. K. Skinner E-Box and Cyclic Adenosine Monophosphate Response Elements Are Both Required for Follicle-Stimulating Hormone-Induced Transferrin Promoter Activation in Sertoli Cells Endocrinology, March 1, 1999; 140(3): 1262 - 1271. [Abstract] [Full Text]

				L. Gnessi, A. Fabbri, and G. Spera Gonadal Peptides as Mediators of Development and Functional Control of the Testis: An Integrated System with Hormones and Local Environment Endocr. Rev., August 1, 1997; 18(4): 541 - 609. [Abstract] [Full Text] [PDF]

				S. Maiti, J. Doskow, S. Li, R. P. Nhim, J. S. Lindsey, and M. F. Wilkinson The Pem Homeobox Gene. ANDROGEN-DEPENDENT AND -INDEPENDENT PROMOTERS AND TISSUE-SPECIFIC ALTERNATIVE RNA SPLICING J. Biol. Chem., July 19, 1996; 271(29): 17536 - 17546. [Abstract] [Full Text] [PDF]