Inhibitory Actions of Pineal Indoles on Steroidogenesis in Isolated Rat Leydig Cells

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Abstract
The inhibition elicited by pineal indoles on testosterone production by isolated rat Leydig cells could not be overcome by a maximally active dose of luteinizing hormone (LH), and dibutyryl-CAMP-induced steroidogenesis was also suppressed, suggesting that the indoles did not exert their effect through an interaction with LH receptors on Leydig cells. Pregnenolone-induced progesterone secretion was unaffected, indicating that the activity of 3P-dehydrogenase was not altered. Methoxytryptamine (MTN) at a dose of I mM decreased progesterone-induced 17αL- hydroxyprogesterone secretion by 50%, suggesting that the enzyme 17α-hydroxylase was inhibited. The inhibition caused by other pineal indoles was either very slight or absent. MTN reduced 17α-hydroxyprogesterone-induced androstenedione production by 65%, methoxytryptophol (MTOL) and melatonin (MEL) by 35%, and methoxyindoleacetic acid (MIAA) and hydroxyindoleacetic acid (HIAA) by 10%, revealing an inhibition of 17–20 desmolase. The reduction of androstenedioneinduced testosterone production by MTN infers inhibition of 17-ketoreductase activity. However, testosterone production induced by either dehydroepiandroster- one or androstenedione was unaffected by other indoles. The data suggest that MTN inhibited 17α-hydroxylase, 17–20 desmolase, and 17-ketoreductase while MEL, MTOL, MIAA, and HIAA inhibited only 17–20 desmolase. The highest potency of MTN in inhibiting enzymes on the testosterone biosynthestic pathway was reflected in its greatest inhibition of testosterone production. On the other hand, MIAA and HIAA had the lowest potency in inhibiting the enzymes and testosterone production while MEL and MTOL had intermediate potencies.