Phthalate ester effects on rat Sertoli cell function in vitro: Effects of phthalate side chain and age of animal

Heindel, JJ; Powell, CJ

HERO ID

675196

Reference Type

Journal Article

Year

1992

Language

English

PMID

1321518

HERO ID 675196
In Press No
Year 1992
Title Phthalate ester effects on rat Sertoli cell function in vitro: Effects of phthalate side chain and age of animal
Authors Heindel, JJ; Powell, CJ
Journal Toxicology and Applied Pharmacology
Volume 115
Issue 1
Page Numbers 116-123
Abstract Mono(2-ethylhexyl) phthalate (MEHP), the active metabolite of the testicular toxicant di(2-ethylhexyl) phthalate, inhibits FSH-stimulated rat Sertoli cell cAMP accumulation, stimulates basal lactate production, and decreases intracellular ATP levels in vitro. Dibutyl phthalate and dipentyl phthalate but not diethyldimethyl or dipropyl are also age-dependent testicular toxicants in vivo. We therefore examined the effect of animal age and phthalate monoester on the Sertoli cell FSH-stimulated cAMP accumulation, lactate secretion, and ATP levels in order to determine if these effects are part of the mechanism of action of phthalate esters in vivo. MEHP, monobutyl and monopentyl phthalates but not the monoethyl, monomethyl, or monopropyl phthalates inhibited FSH-stimulated cAMP accumulation, a segregation which matches the in vivo toxicity potential of these agents. MEHP and monopentyl, but not monobutyl phthalates, also stimulated Sertoli cell lactate secretion. The effect of the active phthalates on FSH-stimulated cAMP accumulation and lactate secretion is not dependent on age of animal over a range of 13-80 days, suggesting that the age-related toxicity in vivo may be related to differences in metabolism and disposition rather than tissue sensitivity. Since the ED50 of MEHP inhibition of cAMP accumulation and lactate secretion is similar, these two effects may be related to a common initial effect of the active phthalates. Inhibition of intracellular ATP levels is specific for MEHP and is lost with age (greater than 28 days of age) and thus is not likely to be an essential part of the in vivo mechanism of action of phthalate diesters.
Doi 10.1016/0041-008X(92)90374-2
Pmid 1321518
Wosid WOS:A1992JC47400015
Url http://www.sciencedirect.com/science/article/pii/0041008X92903742
Is Certified Translation No
Dupe Override No
Comments Authoring Organization: MONSANTO APPLIED SCI DIV
Is Public Yes
Language Text English
Keyword 1498-64-2
Is Qa No