Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell Development but Inhibiting Spermatogenesis in Rats

Abstract

Background: Piperine is the primary pungent alkaloid isolated from the fruit of black peppercorns. Piperine is used frequently in dietary supplements and traditional medicines. The objective of the present study was to investigate the effects of piperine on the testis development in the pubertal rat.Methods: Piperine (0 or 5 or 10 mg/kg) was gavaged to 35-day-old male Sprague-Dawley rats for 30 days. Serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The development of adult Leydig cell population was also analyzed 65 days postpartum. For in vitro studies, immature Leydig cells were isolated from 35-day-old male rats and treated with 50 μM piperine in the presence of different steroidogenic stimulators/substrates for 24 h.Results: Thirty-day treatment of rats with piperine significantly increased serum T levels without affecting LH concentrations. However, piperine treatment reduced serum FSH levels. Consistent with increase in serum T, piperine increased Leydig cell number, cell size, and multiple steroidogenic pathway proteins, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, 17α-hydroxylase/20-lyase, and steroidogenic factor 1 expression levels. Piperine significantly increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phosphos-AKT2 (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Interestingly, piperine inhibited spermatogenesis. Piperine in vitro also increased androgen production and stimulated cholesterol side-chain cleavage enzyme and 17α-hydroxylase/20-lyase activities in immature Leydig cells.Conclusion: Piperine stimulates pubertal Leydig cell development by increasing Leydig cell number and promoting its maturation while it inhibits spermatogenesis in the rat. ERK1/2 and AKT pathways may involve in the piperine-mediated stimulation of Leydig cell development.

Piperine-A Major Principle of Black Pepper: A Review of Its Bioactivity and Studies

“…Similar effects of piperine were recently reported for pubertal rats administered with piperine (5 and 10 mg/kg) for 30 days. In the mentioned study, piperine increased testosterone (T) and follicle-stimulating hormone (FSH) levels, number and size of Leydig cells, but negatively affected spermatogenesis [84]. This was partially opposite to the results of the earlier study, which reported only negative effects of piperine to testes, and performed the same treatment of mature male albino rats (administered for 30 days at the same doses of 5 and 10 mg/kg).…”

“…It activates transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, a novel anti-epileptogenic target, indicating the anti-seizure effects [83]. Chen et al [84] recently reported the effects of piperine (5 and 10 mg/kg) on the testis development in the pubertal rat, where piperine increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phospho-AKT2 (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis in rats, showing a stimulating effect to the Leydig cell development.…”

Piperine: A review of its biological effects

“…of piperine did not cause any negative effects on reproductive functions and the male germ cells, spermatogenesis, and epididymis enzymes. However, higher doses caused significant reduction in epididymis enzymatic functions, sialic levels, and development of testis in pubertal rats (Chen et al, 2018; D'cruz & Mathur, 2005; Daware, Mujumdar, & Ghaskadbi, 2000). In an earlier report, researchers observed a partial to severe degeneration of germ cells when albino rats were fed with 5 and 10 mg/kg b.w.…”

Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway

“…Deng et al ( 26 ) demonstrated that activation of the PI3K/AKT signaling pathway promoted myocardial survival by attenuating ERS-induced apoptosis. Moreover, there is a close relationship between PIP and the activation of the PI3K/AKT pathway ( 13 ). Chen et al ( 13 ) revealed that PIP promoted Leydig cell development but inhibited spermatogenesis in rats by activating AKT.…”

“…Moreover, there is a close relationship between PIP and the activation of the PI3K/AKT pathway ( 13 ). Chen et al ( 13 ) revealed that PIP promoted Leydig cell development but inhibited spermatogenesis in rats by activating AKT. Consistent with a previous study ( 13 ), the present study validated that pretreatment with PIP not only inhibited apoptosis induced by H/R injury, but also upregulated the expression of p-PI3K and p-AKT.…”