The effect of calcium ions on testosterone production in Leydig cells from rat testis

Abstract

Leydig-cell suspensions, prepared from rat testes, were incubated with different amounts of Ca2+ with and without added luteinizing hormone. The basal testosterone production in the absence of luteinizing hormone was unaffected by the Ca2+ concentration in the incubation medium. The luteinizing hormone-stimulated testosterone production, however, was progressively decreased in the absence of Ca2+ to one-third of that with 2.50 mM-Ca2+. This decrease in luteinizing hormone-stimulated testosterone production was independent of the different concentrations of luteinizing hormone (0-10mug/ml) used and could be restored by the addition of Ca2+ to the incubation medium. The restoration of the stimulation was achieved within 30 min after the addition of Ca2+ to the medium. Activation of cyclic AMP-dependent protein kinase by luteinizing hormone was not decreased by omission of Ca2+ from the incubation medium, suggesting that Ca2+ may be involved in steroidogenesis at a stage beyond the luteinizing hormone receptor-adenylate cyclase-protein kinase system.

Protein Kinase C Increases 11β‐Hydroxysteroid Dehydrogenase Oxidation and Inhibits Reduction in Rat Leydig Cells

“…PKC signaling is activated by arachidonic acid and the latter induces steroidogenic acute regulatory protein, leading to increased steroidogenesis (Janzen et al, 1976;Gudermann et al, 1992b). Calcium fluxes, triggered by LH binding, have also been shown to activate Leydig cell steroidogenesis (Janzen et al, 1976;Sullivan and Cooke, 1985;Gudermann et al, 1992b;Wang et al, 2000). In the present study, we observed that cal-cium-dependent signal transduction was required for stimulation of 11␤HSD reductive activity.…”

“…An indirect mechanism is seen, for example, in the case of testosterone itself, which has been shown to decrease 11␤HSD oxidative activity and increase reductive activity (Gao et al, 1997). Both PKC and calcium signaling have been shown to regulate testosterone production (Janzen et al, 1976;Nikula et al, 1987;Gudermann et al, 1992b). Both PKC and calcium/ calmodulin modulators could affect 11␤HSD via the action of testosterone.…”

“…PKC, a key signaling system in many cell types, is known to be present in Leydig cells where it regulates testosterone biosynthesis (Nikula et al, 1987). PKC signaling is activated by arachidonic acid and the latter induces steroidogenic acute regulatory protein, leading to increased steroidogenesis (Janzen et al, 1976;Gudermann et al, 1992b). Calcium fluxes, triggered by LH binding, have also been shown to activate Leydig cell steroidogenesis (Janzen et al, 1976;Sullivan and Cooke, 1985;Gudermann et al, 1992b;Wang et al, 2000).…”

“…Calcium is believed to be a second messenger controlling steroidogenesis in Leydig cells (Janzen et al, 1976;Gudermann et al, 1992b). Two basic mechanisms contribute to the elevation of cytosolic calcium levels: 1) movement of calcium from the extracellular space into the cell through the cell membrane, and 2) release of calcium from intracellular storage sites.…”

“…Because these hormones regulate Leydig cell function through more than one intracellular signal transduction pathway, including the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA; Cooke, 1996), calcium (Janzen et al, 1976;Gudermann et al, 1992a,b), protein kinase C (PKC; Nikula et al, 1987;Majercik and Puett, 1991), and tyrosine protein kinase (Wuerther et al, 1995), 11␤HSD oxidation and reduction may be separately controlled. In the present investigation, after testing a series of modulators of PKA, calcium, PKC, and tyrosine protein kinase, we demonstrated that 11␤HSD oxidation and reduction in rat Leydig cells are controlled in opposing fashion by PKC and calcium-dependent signaling.…”