Effects of the calcium-channel blockers cobalt, verapamil, and D600 on Leydig cell steroidogenesis

• Published in: Biology of reproduction Vol. 28; no. 3; pp. 528 - 535
• Main Author: Moger, W H
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01-04-1983
• Subjects: Androgens - biosynthesis; Animals; Calcium Channel Blockers - pharmacology; Cobalt - pharmacology; Gallopamil - pharmacology; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Mice; Phosphoprotein Phosphatases - antagonists & inhibitors; Protein Biosynthesis; Verapamil - analogs & derivatives; Verapamil - pharmacology
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod28.3.528

The effects of various calcium-channel blockers on androgen production by collagenase-dispersed mouse testicular interstitial
cells were investigated. Cobalt caused a dose-dependent inhibition of the maximum rate of luteinizing hormone (LH)-stimulated
androgen production without altering the concentration of LH required for half maximum stimulation (EC50). Nickel and manganese
also inhibited LH-stimulated steroidogenesis but were less potent than cobalt. The major site at which cobalt treatment inhibited
steroidogenesis was beyond cAMP formation and before 3 beta-hydroxysteroid dehydrogenase. This conclusion was based on the
observation that cobalt inhibited dibutyryl cAMP-stimulated androgen production but did not affect protein synthesis and pregnenolone-supported
androgen production. Androgen production was unaffected by the organic calcium-channel blockers verapamil and the (+) and
(-) enantiomers of D600 at concentrations less than 0.1 mM. At a concentration of 0.1 mM the organic calcium-channel blockers
inhibited LH- and dibutyryl cAMP-stimulated androgen production. Unlike cobalt, the organic calcium-channel blockers also
inhibited pregnenolone-supported androgen production and reduced the rate of protein synthesis. Similarities between the effects
of cobalt in the present study and previous reports of the effects of reduced extracellular calcium concentrations on androgen
production suggest that cobalt inhibits androgen production as a result of its ability to block calcium influx. The calcium
channels involved in the steroidogenic process appear, however, to be relatively insensitive to the organic calcium-channel
blockers.