Factors affecting Sertoli cell function in the testis.
The Sertoli cell is the primary target for FSH action in the mammalian testis. These cells contain the majority of testicular plasma membrane receptors for this hormone. Receptor occupancy is directly correlated with a stimulation of adenylyl cyclase and a decrease in the activity of a cytoplasmic Ca++-sensitive cAMP phosphodiesterase. Regulation of these two enzymes allows increased intracellular accumulation of cAMP, activation of cAMP-dependent protein kinase and phosphorylation of a variety of protein substrates. All of these events occur within the first 30 min following exposure of isolated Sertoli cells to FSH. RNA and protein synthesis are also enhanced by FSH. Previous studies have suggested that this gonadotropin may augment the overall cellular synthesis of proteins. Our results reveal that protein kinase inhibitor (PKI) is selectively elevated by FSH both in vivo and in vitro. PKI thus becomes the initial intracellular protein whose synthesis is under FSH control. In addition to effects on protein synthesis, FSH also positively modulates the secretion of several specific proteins. One of the proteins in this latter category is androgen binding protein (ABP). Again, regulation can be observed both in vivo and in vitro. Elevated synthesis of PKI occurs prior to demonstrable secretion of ABP. Both of these events occur subsequent to the effects of FSH on cAMP metabolism. Indeed cAMP (or any of several nonhydrolyzable derivatives) can substitute for FSH in vitro. The temporal sequence of events subsequent to hormone binding and cAMP production are identical, but occur more rapidly. Together these data support the hypothesis that most of the biochemical steps leading to the synthesis and secretion of proteins by FSH are regulated by elevated levels of cAMP.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000727:Androgen-Binding Protein / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011962:Receptors, FSH; D012708:Sertoli Cells / Q000187:drug effects / Q000502:physiology*; D013091:Spermatogenesis / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology
D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D011962:Receptors, FSH; C015482:protein kinase modulator; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D011494:Protein Kinases; D000262:Adenylyl Cyclases