Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary–gonadal axis and Leydig cell steroidogenesis

Abstract

Procymidone is a fungicide with anti-androgenic properties, widely used to protect fruits from fungal infection. Thereby it contaminates fruit products prepared for human consumption. Genistein-containing soy products are increasingly used as food additives with healthpromoting properties. Therefore we examined the effects of long-term dietary administration (3 months) of the anti-androgen procymidone (26·4 mg/animal per day) or the phytoestrogen genistein (21·1 mg/animal per day) to rats on the pituitary-gonadal axis in vivo, as well as on Leydig cell steroidogenesis and on spermatogenesis ex vivo. The procymidone-containing diet elevated serum levels of LH and testosterone and, furthermore, Leydig cells isolated from procymidone-treated animals displayed an enhanced capacity for producing testosterone in response to stimulation by hCG or dibutyryl cAMP, as well as elevated expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450 scc) and cytochrome P450 17 (P450c17). In contrast, the rate of DNA synthesis during stages VIII and IX of spermatogenesis in segments of seminiferous tubules isolated from genistein-treated rats was decreased without accompanying changes in the serum level of either LH or testosterone. Nonetheless, genistein did suppress the ex vivo steroidogenic response of Leydig cells to hCG or dibutyryl cAMP by down-regulating their expression of P450 scc. Considered together, our present findings demonstrate that long-term dietary administration of procymidone or genistein to rats exerts different effects on the pituitarygonadal axis in vivo and on Leydig cell steroidogenesis ex vivo. Possibly as a result of disruption of hormonal feedback control due to its anti-androgenic action, procymidone activates this endocrine axis, thereby causing hypergonadotropic activation of testicular steroidogenesis. In contrast, genistein influences spermatogenesis and significantly inhibits Leydig cell steroidogenesis ex vivo without altering the serum level of either LH or testosterone.

Origin, Development and Regulation of Human Leydig Cells

“…In addition, possible reduction of the capacity of fetal human Leydig cells to produce androgens induced by xenobiotics (see, for example [75,76]), which may lead to incomplete masculinization of male fetuses and various malformations in the reproductive tract, should be explored.…”

Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

“…The effect of (Bu) 2 cAMP on the level of expression of cytochrome P450c17 by PFLCs was examined by PAGE/Western blotting as described earlier (Svechnikov et al, 2003;Svechnikov et al, 2005). Briefly, PFLCs stimulated with or without (Bu) 2 cAMP for 4 days were washed …”

Reference Profile Correlation Reveals Estrogen-like Trancriptional Activity of Curcumin

“…In addition to receptor dependent functions there is growing evidence that phytoestrogens reduce local production of estrogens by inhibiting the activity of key steroidogenic enzymes involved in the synthesis of estradiol (E2) [7,8]. Phytoestrogens could diminish local estrogen levels by inhibiting their converting enzymes thereby reducing the proliferation stimulus and thus protect against breast cancer progression.…”