On the mechanism of action of lead in the testis: in vitro suppression of FSH receptors, cyclic AMP and steroidogenesis. [Rats]
The purpose of the present study was to determine by in vitro methods, if Pb acts by interfering directly with hormone binding, cyclic AMP production and steroidogenic enzyme activity. Sertoli cells were isolated from testes of prepubertal rats and cultured in the presence of 2.64 x 10/sup -4/ M of either NaAc (control) or PbAc for 1, 4, 24, 48, 96 or 144 hr. There was no reduction in FSH binding and in FSH-induced cyclic AMP after a 1-4 hr exposure to Pb. After a 24-hr exposure to Pb, the cells exhibited a 10-20% decrease in FSH binding and cyclic AMP production and after 96 hr there was a 75% decrease in these 2 parameters. The inhibition was greater in cells from 16 day old than from 20 day old rats, so that in the former, after a 144 hr exposure the FSH-induced cyclic AMP of the Pb exposed cells was only 3% of the amount produced by the NaAc exposed cells (i.e. a 97% inhibition). After in vitro exposure to Pb for 48 hr, the steroidogenic activity (progesterone conversion to steroid metabolites) of Sertoli cells was significantly reduced and their steroidogenesis was no longer stimulated by FSH. A crude testicular enzyme preparation containing 3..beta..-hydroxysteroid dehydrogenase (3..beta..-HSD) exhibited approximately 25% reduction in activity if the assay buffer contained PbCl/sub 2/ instead of the equivalent in NaCl. Prolonged in vivo exposure to Pb resulted in approximately 50% reduction in 3..beta..-HSD activity. This is the first indication that in the testis Pb may act directly (immediate effect) by suppressing enzyme activities, and indirectly (long term effect) by reducing gonadotropin-receptor binding and the resultant cyclic AMP production.
- Research Organization:
- Univ. of Western Ontario, London, Canada
- OSTI ID:
- 5893894
- Journal Information:
- Life Sci.; (United States), Vol. 32:17
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ENZYME ACTIVITY
INHIBITION
FSH
CHEMICAL BONDS
LEAD
BIOLOGICAL EFFECTS
AMP
BIOSYNTHESIS
INJURIES
RATS
REPRODUCTION
SENSITIVITY
STEROIDS
TESTES
ANIMALS
BODY
ELEMENTS
GONADOTROPINS
GONADS
HORMONES
MALE GENITALS
MAMMALS
METALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
RODENTS
SYNTHESIS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)