Endocrinology, Vol 124, 3015-3024, Copyright © 1989 by Endocrine Society

ARTICLES

Regulation of Sertoli cell differentiated function: testicular transferrin and androgen-binding protein expression

MK Skinner, SM Schlitz and CT Anthony
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

The regulation of Sertoli cell function was investigated through an examination of the effects of various hormones, regulatory agents, and culture conditions on testicular transferrin and androgen-binding protein (ABP) synthesis and steady state levels of mRNA. FSH stimulated both transferrin and ABP production 2-fold above control levels. Interestingly, FSH had a differential effect on transferrin and ABP mRNA levels, with 1.25- and 2.0-fold respective increases in steady state levels of mRNA. Insulin and retinol stimulated both transferrin and ABP synthesis in a similar manner. Testosterone had no significant effect on either transferrin or ABP mRNA levels or synthesis. Maximum stimulation of both transferrin and ABP production occurred when Sertoli cell cultures were treated with a combination of FSH, insulin, and retinol, which resulted in a greater than 4-fold stimulation of synthesis and 2-fold stimulation of gene expression. Optimal transferrin and ABP secretion occurred between days 4-6 of Sertoli cell culture and subsequently declined. Sertoli cell number decreased with time in culture, such that approximately a 50% loss of cells was observed after 10 days of culture. The responsiveness of Sertoli cells to regulatory agents was altered by cell density, with a maximum responsiveness achieved at a density of 12 micrograms DNA/2 cm2 for both transferrin and ABP. As the cell density deviated from this level the responsiveness of cells to regulatory agents decreased and approached control values. These observations indicate that the culture conditions and the method of data normalization are important parameters in an analysis of the hormonal regulation of Sertoli cell function. FSH actions on Sertoli cells increased both cellular and excreted cAMP levels but had no effect on cGMP levels. (Bu)2 cAMP affected transferrin and ABP mRNA levels and synthesis in a similar manner, with approximately a 3-fold increase in synthesis and a 1.5- fold increase in steady state levels of mRNA. The minimum and maximum effective concentrations of (Bu)2AMP for both proteins were 1 and 10 microM, respectively. Observations imply that regulatory agents that act via a cAMP-mediated signal transduction mechanism, such as FSH, will probably have similar actions on transferrin and ABP production. In addition, data obtained with insulin and retinol indicate that transferrin and ABP production can be similarly regulated with cAMP- independent signal transduction mechanisms. Results indicate that transferrin and ABP mRNA levels and synthesis are regulated in a coordinate manner with the regulatory agents and culture conditions evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				R.-S. Wang, S. Yeh, L.-M. Chen, H.-Y. Lin, C. Zhang, J. Ni, C.-C. Wu, P. A. di Sant'Agnese, K. L. deMesy-Bentley, C.-R. Tzeng, et al. Androgen Receptor in Sertoli Cell Is Essential for Germ Cell Nursery and Junctional Complex Formation in Mouse Testes Endocrinology, December 1, 2006; 147(12): 5624 - 5633. [Abstract] [Full Text] [PDF]

				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]

				S. J Meachem, S. M Ruwanpura, J. Ziolkowski, J. M Ague, M. K Skinner, and K. L Loveland Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation J. Endocrinol., September 1, 2005; 186(3): 429 - 446. [Abstract] [Full Text] [PDF]

				T. Muir, I. Sadler-Riggleman, and M. K. Skinner Role of the Basic Helix-Loop-Helix Transcription Factor, Scleraxis, in the Regulation of Sertoli Cell Function and Differentiation Mol. Endocrinol., August 1, 2005; 19(8): 2164 - 2174. [Abstract] [Full Text] [PDF]

				D. M. Selva, K. N. Hogeveen, and G. L. Hammond Repression of the Human Sex Hormone-binding Globulin Gene in Sertoli Cells by Upstream Stimulatory Transcription Factors J. Biol. Chem., February 11, 2005; 280(6): 4462 - 4468. [Abstract] [Full Text] [PDF]

				J. J. Buzzard, N. G. Wreford, and J. R. Morrison Thyroid Hormone, Retinoic Acid, and Testosterone Suppress Proliferation and Induce Markers of Differentiation in Cultured Rat Sertoli Cells Endocrinology, September 1, 2003; 144(9): 3722 - 3731. [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]

				F. Munell, C. A. Suarez-Quian, D. M. Selva, O. M. Tirado, and J. Reventos Androgen-Binding Protein and Reproduction: Where Do We Stand? J Androl, September 1, 2002; 23(5): 598 - 609. [Full Text] [PDF]

				J. Chaudhary and M. K. Skinner Role of the Transcriptional Coactivator CBP/p300 in Linking Basic Helix-Loop-Helix and CREB Responses for Follicle-Stimulating Hormone-Mediated Activation of the Transferrin Promoter in Sertoli Cells Biol Reprod, August 1, 2001; 65(2): 568 - 574. [Abstract] [Full Text] [PDF]

				J. Chaudhary, J. Johnson, G. Kim, and M. K. Skinner Hormonal Regulation and Differential Actions of the Helix-Loop-Helix Transcriptional Inhibitors of Differentiation (Id1, Id2, Id3, and Id4) in Sertoli Cells Endocrinology, May 1, 2001; 142(5): 1727 - 1736. [Abstract] [Full Text]

				J. E. Ottenweller, M.-T. Li, W. Giglio, R. Anesetti, L. M. Pogach, and H. F.S. Huang Alteration of Follicle-Stimulating Hormone and Testosterone Regulation of Messenger Ribonucleic Acid for Sertoli Cell Proteins in the Rat During the Acute Phase of Spinal Cord Injury Biol Reprod, September 1, 2000; 63(3): 730 - 735. [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]

				M. F. Carlevaro, A. Albini, D. Ribatti, C. Gentili, R. Benelli, S. Cermelli, R. Cancedda, and F. D. Cancedda Transferrin Promotes Endothelial Cell Migration and Invasion: Implication in Cartilage Neovascularization J. Cell Biol., March 24, 1997; 136(6): 1375 - 1384. [Abstract] [Full Text] [PDF]