In hypophysectomized rats, treatment with pregnenolone (pregn-5-en-3β-ol-20-one) for 14 days prevented testicular atrophy, maintained spermatogenesis but did not counteract Leydig cell atrophy. Spermatogenic activity was abolished when a 16α-nitrile group was attached to the pregnenolone molecule, but pregnenolone-16α-carbonitrile (PCN) did not interfere with the spermatogenic effect of pregnenolone. These results are discussed in view of the fact that PCN inhibits intoxication with excess amounts of many steroids (e.g. anaesthesia due to heavy overdosage with progesterone or hydroxydione), whereas steroid hormones, administered at doses necessary to maintain physiological functions, are virtually resistant to this type of catatoxic action, which usually takes the form of enhanced metabolic degradation and/or substrate excretion.
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