RGD Reference Report - Effect and mechanism of cadmium on the progesterone synthesis of ovaries. - Rat Genome Database

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Effect and mechanism of cadmium on the progesterone synthesis of ovaries.

Authors: Zhang, W  Jia, H 
Citation: Zhang W and Jia H, Toxicology. 2007 Oct 8;239(3):204-12. Epub 2007 Jul 13.
RGD ID: 4835171
Pubmed: PMID:17719163   (View Abstract at PubMed)
DOI: DOI:10.1016/j.tox.2007.07.007   (Journal Full-text)

The paper presents results of the effect of cadmium on the progesterone synthesis of ovaries. In the current study, we investigated whether Cd also disrupts progesterone synthesis via steroidogenic acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage (P450scc), which play important roles in progesterone synthesis. The Wistar rats were exposed to cadmium in vivo (at 2.5, 5, 7.5mg/kg, as a single s.c. dose). We showed that the serum P(4) and granule cells P(4) of rats were significantly lower than control group. Ovaries granule cells were incubated in Dulbecco-modified Eagle medium +15% fetal bovine serum with 0, 10, 20, or 40 microM CdCl(2) in vitro, progesterone levels were declined in a dose-dependent manner. Our data showed that the expression of StAR and P450scc in vivo or in vitro were inhibited when treated with CdCl(2) (p<0.05). Coculture with 8-bromo-cAMP enhanced progesterone secretion in untreated cultures and reversed the decline in progesterone secretion induced by CdCl(2) treatment; the expression of StAR mRNA and P450scc mRNA in 8-Br-cAMP+40 microM CdCl(2) were significantly higher than 40 microM CdCl(2), and were lower than control group. We concluded that StAR, which delivers cholesterol to the inner mitochondrial membrane, is one site at which Cd interferes with progesterone production in cultured rats ovarian granule cells; P450scc, which conveys cholesterol to pregnenolone, is anther site. The mechanisms were mainly controlled by the cAMP-dependent pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cyp11a1Ratcellular response to cadmium ion  IEP  RGD 
StarRatcellular response to cadmium ion  IEP  RGD 
Cyp11a1Ratcellular response to cAMP  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp11a1  (cytochrome P450, family 11, subfamily a, polypeptide 1)
Star  (steroidogenic acute regulatory protein)


Additional Information