Effects of Forskolin on Androgen Production by Mouse Interstitial Cells in Vitro. Interactions with Luteinizing Hormone and Isoproterenol

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Abstract
Micromolar concentrations of the diterpene forskolin [isolated from the roots of Coleus forskohlii, activates adenylate cyclase in cells and cell membranes] stimulated androgen production by collagenase-dispersed mouse testicular interstitial cells. With maximum stimulatory concentrations, forskolin and luteinizing hormone (LH) increased androgen production with similar time courses and to similar extents. The concentration of LH required for half-maximum stimulation (EC50) was reduced .apprx. 10-fold in the presence of forskolin whereas maximum androgen production was unaffected. LH reduced the EC50 for forskolin .apprx. 5-fold. The observed synergism between LH and forskolin was most likely at the level of cAMP generation as forskolin did not alter the EC50 for dibutyryl cAMP activation of androgen production. When cells were allowed to attach to the wells of tissue culture plates for 3 h prior to stimulation, isoproterenol treatment induced a small increase in androgen producton when, and only when, submaximum concentrations of forskolin were also present. The increase in androgen production attributable to isoproterenol was blocked by simultaneous exposure to the .beta.-antagonist propranolol. When cells were immediately (0 h) exposed to forskolin and isoproterenol, no interaction was observed. These results demonstrate the ability of forskolin treatment to reveal the presence of latent .beta.-adrenergic receptors. They also indicate that isolated adult mouse Leydig cells may not contain such receptors.