Wafula Nyongesa Albert, Muge Edward, Nyaboga Evans
Consumption of fresh khat leaves has been shown to impair male reproductive function. (-)-cathinone, the principal alkaloid, is known for its euphoric and psychostimulatory effects. High dose and chronicity of exposure to khat and (-)-cathinone is associated with impaired reproductive hormone synthesis in experimental animal. It is currently not known whether expression of genes encoding for specific testicular steroidogenic enzymes are involved. The present study examined the effects of (-)-cathinone from fresh khat leaves on mRNA expression of (3b hydroxy steroid dehydrogenase [3b-HSD] type I and 17b hydroxy- steroid dehydrogenase [17b-HSD] type I) genes and intra-testicular hormone production in vervet monkey testis. Eight male animals divided into 4 groups, were administered (-)-cathinone at 0.8, 3.2 and 6.4 mg/kg body weight, respectively while control group received normal saline. The mRNA expression of steroidogenesis-associated genes using semi-quantitative reverse transcription and real-time quantitative polymerase chain reaction as well as ex vivo measurement of intracellular progesterone, androstenedione and testosterone were investigated. Results showed significant (P < 0.05) increase in mRNA expression of 3b-HSD type I and 17b- HSD type I at 3.2 and 6.4 mg/kg body weight of (-)-cathinone compared to the control but at 0.8 mg/kg body weight, the changes were not significant. There was increased intra-testicular progesterone, androstenedione and testosterone in cultured interstitial cells exposed to luteinizing hormone but significantly suppressed when co-treated with (-)-cathinone at 100 µl of 6.4 mg/kg body weight. It appears (-)-cathinone at high doses affect steroidogenesis and thus directly or indirectly influence spermatogenesis in habitual male khat users. Key words: (-)-Cathinone, hydroxysteroid dehydrogenase, real-time polymerase chain reaction (PCR), sex steroid biosynthesis, vervet monkey.