Mechanism of down regulation of luteinizing hormone receptors and steroidogenesis in corpora lutea |
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Authors: | Rajan R Dighe N R Moudgal |
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Institution: | (1) Department of Biochemistry, Indian Institute of Science, 560 012 Bangalore, India |
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Abstract: | The mechanism of ‘down regulation’ of luteinizing hormone receptors was investigated in pseudopregnant rats using a modified
radioimmunoassay capable of measuring endogenous tissue-bound hormone. Treatment of pseudopregnant animals with a desensitizing
dose (desensitization treatment) of human chorionic gonadotropin resulted in a decrease in receptor concentration. This decrease
was prevented if the animals were treated prior to the desensitization treatment with indomethacin, an inhibitor of prostaglandin
biosynthesis, suggesting a role for prostaglandins in down regulation. The desensitization treatment resulted in a time-dependent
decrease in subsequent responsiveness of the tissue to luteinizing hormone. Basal progesterone production rate was also decreased
following desensitization. Total tissue cholesterol was found to be decreased following desensitization treatment, without
any change in the ratio of free to esterified cholesterol. Mitochondrial cholesterol was significantly reduced and pregnenolone
production by the mitochondria of desensitized corpora lutea was also markedly reduced. However, when cholesterol was added
to the mitochondria of desensitized corpora lutea, pregnenolone production was increased, reaching values almost equal to
that shown by the control mitochondria. These results show that decrease in the responsiveness following desensitization treatment
is due to, besides receptor loss, decrease in tissue cholesterol, in particular mitochondrial cholesterol. The cholesterol
side chain cleavage activity, although low, appears to be functionally intact; the low activity could be attributed to low
levels of mitochondrial cholesterol. |
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Keywords: | Down regulation desensitization luteinizing hormone steroidogenesis |
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