Effect and mechanism of cadmium on the progesterone synthesis of ovaries.
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.
Zhang
Wenchang
W
Department of Occupational and Environmental, School of Public Health, Fujian Medical University, Major in Reproduction Toxicology and Enviroment Endocrine Disrupting Chemicals, Fujian, China. Wenchang58@126.com
Jia
Haimei
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood; D011372:Progestins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
D004785:Environmental Pollutants; D010750:Phosphoproteins; D011372:Progestins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D019256:Cadmium Chloride