Trafficking inside cells

The formation of androgens from pregnenolone in the smooth endoplasmic reticulum of Leydig cells is the result of interactions between different membrane-bound enzymes with steroids as mobile elements. Within the smooth endoplasmic retic-ulum, to a great extent trafficking of the steroids is influenced by the affinities of the enzymes and binding properties of other membrane components. Apart from these binding entities, the movements of steroids in tissues appear to depend mostly on diffusion (reviewed by Mendel 1989). There are no reports that steroids are secreted like proteins that are released from vesicles after fusion with the cell membrane. Conjugated steroids, however, cannot easily pass cell membranes by diffusion and for this class of steroids specific transport systems are required (Mulder et al. 1973). Binding proteins for androgens or other steroids can play an important role in decreasing the concentration of unbound steroids outside the cell and so enhance the diffusion process, but there are no indications that such proteins are also important inside the cell. Another argument against an important role of specific transport systems for steroids in Leydig cells is the observation that secretion of pregnenolone that is normally very low, can become as high as secretion of testosterone when metabolism of pregnenolone to testosterone is inhibited (van Haren etal. 1989). Although diffusion is probably the main driving force for steroid trafficking within the cell, it has been shown that multiple-drug resistance proteins in the plasma membrane can increase the rate of transport of steroids over the plasma membrane (Ueda et al. 1992). If these transport proteins can also transport androgens and are localised in the Leydig cell, they could aid in the secretion of androgens. Alternatively these steroid transport proteins could alter the steady state concentrations of androgens in target cells. However, since the transport activities of these proteins have mainly been shown for corticosteroids and their derivatives (Gruol and Bourgeois 1997) the relevance of this transport system for androgens is unknown.

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