Effect of lindane on mitochondrial side-chain cleavage of cholesterol in mice

Sircar, S. M.; Lahiri, Pulak

doi:10.1016/0300-483x(90)90005-2

Cited by 21 publications

(8 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lindane inhibited human chorionic gonadotropin-stimulated T production by rat Leydig cells [ 101 , 102 ], suggesting that the compound might affect testicular steroidogenesis [ 105 ]. Indeed, lindane inhibits mouse CYP11A1 activity [ 106 ].…”

Section: Eds With Direct Inhibition On Enzymes For T Biosynthesis mentioning

confidence: 99%

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

2011

Molecules

134

View full text Add to dashboard Cite

The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes.

show abstract

Section: Eds With Direct Inhibition On Enzymes For T Biosynthesis mentioning

confidence: 99%

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

2011

Molecules

134

View full text Add to dashboard Cite

show abstract

“…One report (Walsh and Stocco, 2000) studying mouse Leydig cells, pinpoints this effect to the expression of the StAR gene, which encodes the protein performing the rate limiting step of steroidogenesis. In the female reproductive system, lindane has been shown to inhibit the ovarian side-chain cleavage enzyme (CYP11A1) (Sircar and Lahiri, 1990) as well as placental activity of the aromatase enzyme (CYP19) (Nativelle-Serpentini et al, 2003). In addition to the effects of lindane on reproduction, a few reports indicate that adrenal steroidogenesis may also be a target for toxicity.…”

Section: Introductionmentioning

confidence: 99%

Steroidogenic gene expression in H295R cells and the human adrenal gland: adrenotoxic effects of lindanein vitro

et al. 2006

View full text Add to dashboard Cite

The focus on the refinement, reduction and replacement of animal use in toxicity testing requires the development of cell-based systems that mimic the effects of xenobiotics in human tissues. The human adrenocortical carcinoma cell line, H295R, has been proposed as a model for studies on adrenal steroidogenesis and its disruption. In this study, expression profiles for nine adrenal steroidogenic genes were characterized in H295R cells using real-time RT-PCR. Treatment with forskolin increased cortisol secretion and stimulated transcription of all the steroidogenic genes except SULT2A1. The transcript profile from H295R cells in the presence and absence of forskolin was compared with the transcript profile from human adrenal glands. The gene expression pattern observed in the forskolin-treated H295R cells was more similar to that in the human adrenal gland, than the expression pattern in untreated cells. To examine H295R cells as a possible in vitro system for the assessment of adrenal disruption using molecular endpoints, the insecticide lindane (gamma-hexachlorocyclohexane) was used. In vivo, lindane has been shown to inhibit testicular, ovarian and adrenal steroidogenesis. It was demonstrated that lindane reduced cortisol secretion, downregulated the expression of a subset of the genes encoding steroidogenic enzymes and repressed transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene promoter. Thus the H295R cell line provides a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression. This in vitro test can be used for the rapid detection of adrenal endocrine disruption and as a tool for mechanistic studies.

show abstract

“…In contrast, studies in pregnant mice have shown that Lindane causes a decrease in whelping rate and litter size (Sircar and Lahiri, 1989). These effects of Lindane on fertility may be due to a decreased rate of steroidogenesis (Sircar and Lahiri, 1990), which would adversely affect the steroid hormone-dependent changes necessary for pregnancy maintenance. Lindane has been shown to influence steroid hormone production (Srivastava and Raizada, 1993;Tiemann et al, 1996), althought it did not decrease oestradiol concentrations when given to rodents (Laws et al, 1994).…”

Section: Discussionmentioning

confidence: 98%

Reproductive effects in mink (Mustela vison) exposed to the pesticides Lindane, Carbofuran and Pentachlorophenol in a multigeneration study

Beard

Rawlings²

1998

Reproduction

View full text Add to dashboard Cite

The mammalian reproductive system is sensitive to exposure to endocrine disrupting chemicals, particularly during sexual maturation. The purpose of this study was to examine reproductive function in second and third generation male and female mink exposed to pesticides from conception to maturity. The mink were fed untreated feed or feed treated with Lindane (1 mg kg-1 day-1), Carbofuran (0.05 mg kg-1 day-1) or Pentachlorophenol (1 mg kg-1 day-1) from the time they were weaned. The second generation mink had also been exposed to the pesticides in utero and from their mother's milk as their mothers were similarly fed pesticides, from 3 weeks before breeding. The third generation mink were the offspring of mink (second generation females) who had themselves undergone long-term exposure to pesticides from conception onwards. Blood samples and endocrine tissues were obtained at necropsy from both generations of mink. No overt signs of toxicity were seen. The pesticides did not affect the percentage of mink mated. Lindane treatment reduced the proportion of mated mink that subsequently whelped (P < 0.1) and the litter size of mink that whelped (P < 0.05). Testis size was reduced in the Lindane-treated, third generation males (P < 0.05). Serum concentrations of cortisol, testosterone and oestradiol were not affected by any pesticide treatment; however, thyroxine concentration was reduced by Pentachlorophenol (P < 0.05). In conclusion, exposure of mink to Lindane from conception resulted in a decrease in reproductive efficiency when they were subsequently mated, leading to a 60% reduction in the number of kits born.

show abstract

Effect of lindane on mitochondrial side-chain cleavage of cholesterol in mice

Cited by 21 publications

References 13 publications

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

Steroidogenic gene expression in H295R cells and the human adrenal gland: adrenotoxic effects of lindanein vitro

Reproductive effects in mink (Mustela vison) exposed to the pesticides Lindane, Carbofuran and Pentachlorophenol in a multigeneration study

Contact Info

Product

Resources

About