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Androgens decrease LHRH binding sites in rat anterior pituitary cells in culture.

V Giguere, F A Lefebvre, F Labrie

    Endocrinology
    |January 1, 1981
    PubMed
    Summary
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    This study shows that sex steroids directly reduce LHRH receptors in rat pituitary cells. This reduction correlates with decreased LH release, suggesting a feedback mechanism.

    Area of Science:

    • Endocrinology
    • Neuroendocrinology
    • Molecular Pharmacology

    Background:

    • Luteinizing hormone-releasing hormone (LHRH) regulates reproductive functions.
    • The role of sex steroids in modulating LHRH receptor expression requires further elucidation.

    Purpose of the Study:

    • To investigate the direct effect of sex steroids on LHRH receptors in rat anterior pituitary cells.
    • To determine if changes in LHRH receptor number correlate with altered LH responsiveness.

    Main Methods:

    • Radioligand binding assays using [125I]-[D-Ser(TBU)6]LHRH-EA to quantify LHRH receptors.
    • Treatment of cultured pituitary cells with 5 alpha-dihydrotestosterone.
    • Measurement of LH release in response to LHRH stimulation.

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    Main Results:

    • [125I]-[D-Ser(TBU)6]LHRH-EA bound to high-affinity sites (Kd = 0.25 nM) in rat anterior pituitary cells.
    • Potency of LHRH agonists/antagonists correlated with LH-releasing activity.
    • 48-hour treatment with 100 nM 5 alpha-dihydrotestosterone decreased LHRH receptor number by 40% without altering binding affinity.
    • This decrease in receptors was associated with reduced LH responsiveness to LHRH.

    Conclusions:

    • Sex steroids directly impact the number of pituitary LHRH receptors.
    • Downregulation of LHRH receptors by sex steroids may be a key mechanism for negative feedback in the reproductive axis.