Benzo[a]pyrene Reduces Testosterone Production in Rat Leydig Cells via a Direct Disturbance of Testicular Steroidogenic Machinery

Abstract

Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells.Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins.Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production.Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs.

Disturbance in Testosterone Production in Leydig Cells by Polycyclic Aromatic Hydrocarbons

“…Recently, however, a potent endocrine disrupting mechanism of testosterone production was proposed in Leydig cells after exposure to B[a]P (Chung et al, 2011 …”

The effects of transovarian exposure to <i>p,p’</i>-DDT and <i>p,p’</i>-DDE on avian reproduction using Japanese quails

“…The reduced transcription arises at very low in ovo doses of estrogens and was observed in male hatchlings exposed to o,p' -sist into adulthood (Kamata et al, 2009a(Kamata et al, , 2009b. p,p'-DDT, but not p,p'-DDE, conversely upregulated transcription of the CYP11A1 gene even at the lowest dose CYP11A1 was reported in the ovary and testis of fathead minnows (Pimephales promelas) exposed for 4 days to prochloraz, a fungicide which acts as an aromatase inhibitor and anti-estrogen, and in the testis of rats orally exposed to benzo[a]pyrene (B[a]P) for 90 days (Ankley et al, 2009;Chung et al, 2011). In female fathead minnows transcriptions of the cyp19a1a, cyp17 and follicle stimulating hormone receptor (fshr) genes increased at the same time, and in B[a]P exposed rats serum and pituitary gland levels of luteinizing hormone (LH) increased.…”

Involvement of the Multidrug and Toxic Compound Extrusion Transporter in Testosterone Release from Cultured Pig Leydig Cells

“…The regulation of testosterone production has been extensively reported [4,5,6,7,8,9,10,11]; Leydig cells are responsible for the production of the testicular androgen testosterone in the mammalian testis. A previous report showed that decreased testosterone production in Leydig cells leads to decrease in serum testosterone levels [7].…”

“…A previous report showed that decreased testosterone production in Leydig cells leads to decrease in serum testosterone levels [7]. Testosterone biosynthesis in these cells is induced by stimulation with gonadotropin luteinizing hormone (LH).…”