Proteases are implicated in the changes in the Sertoli cell cytoskeleton elicited by follicle-stimulating hormone or by dibutyryl cyclic AMP.
Follicle-stimulating hormone (FSH) or dibutyryl cyclic AMP (dbcAMP) elicits striking morphological changes in Sertoli cells in culture in serum-free medium, resulting in a transition from an epithelial type of cell association pattern to that of an astrocytic or fibroblast-like cell, with attenuated cytoplasmic extensions between cells, and with diminished F-actin stained stress fibers. These responses of Sertoli cells do not occur in the presence of normal untreated serum, but they do take place in the presence of acid-treated serum which is depleted of antiproteases. The addition of alpha 2-macroglobulin to serum-free medium or to antiprotease-depleted serum resulted in the blockage of morphological responses of Sertoli cells to FSH or to dbcAMP. Changes in pattern of arrangements of F-actin in Sertoli cells in culture, which occur in response to FSH or to dbcAMP, were also prevented by the presence of alpha 2-macroglobulin. Thus, the diminution in bundles of F-actin containing stress fibers, which otherwise takes place in Sertoli cells stimulated by FSH or by dbcAMP, did not occur in cells in culture in the presence of alpha 2-macroglobulin, in the presence or absence of acid-treated serum. The inhibiting effects of dbcAMP on the migration of Sertoli cells in serum-free medium became nondetectable in medium containing normal untreated serum, but remained evident in Sertoli cells in culture in medium containing acid-treated serum depleted of antiproteases. Addition of alpha 2-macroglobulin blocked the inhibitory effects of dbcAMP on Sertoli cell migration. Similarly, the presence of alpha 2-macroglobulin prevented the inhibitory effects of dbcAMP on the contractility of TM4 cells which had been embedded in collagen type-I and incubated in serum-free medium. We discuss the possibility that cellular proteases may be implicated in the disintegration of microfilament bundles, either by favoring depolymerization of actin filaments; by facilitating breakage of the link of the transmembrane molecular assembly between cytoskeletal extracellular matrix components; or by catalyzing a disruption of the modular organization of one or more of the actin cross-linking proteins. By inference, we postulate that morphological responses of Sertoli cells to FSH require the activation of cellular proteases for one or more of these reactions, and that alpha 2-macroglobulin blocks the Sertoli cell morphological responses to FSH by inhibiting the proteases involved.
Tung
P S
PS
Banting and Best Department of Medical Research C.H. Best Institute, University of Toronto, Ontario, Canada.
Burdzy
K
K
Fritz
I B
IB
D000199:Actins / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002417:Cattle / Q000097:blood; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D003599:Cytoskeleton / Q000187:drug effects*; D004338:Drug Combinations; D010450:Endopeptidases / Q000097:blood / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007797:Laminin; D008297:Male; D011509:Proteoglycans; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000187:drug effects; D000511:alpha-Macroglobulins / Q000494:pharmacology
D000199:Actins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D000511:alpha-Macroglobulins; C059485:matrigel; D003994:Bucladesine; D005640:Follicle Stimulating Hormone; D003094:Collagen; D010450:Endopeptidases