Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys

Nick Z. Lu, Cynthia Bethea

    Research output: Contribution to journalArticle

    114 Citations (Scopus)

    Abstract

    Serotonin 5-HT1A receptors play an important role in serotonin neurotransmission and mental health. We previously demonstrated that estradiol (E) and progesterone (P) decrease 5-HT1A autoreceptor mRNA levels in macaques. In this study, we questioned whether E and P regulate 5-HT1A binding and function and Gα subunit protein expression. Quantitative autoradiography for 5-HT1A receptors and G proteins using [3H]8-OH-DPAT and [35S]GTP-γ-S, respectively, was performed on brain sections of rhesus macaques from four treatment groups: ovariectomized controls (OVX), E (28 d), P (28 d), and E (28 d) plus P (the last 14 d) treated. Western blot analysis for Gα subunits was performed on raphe extracts from cynomolgus macaques that were OVX or OVX treated with equine estrogens (EE, 30 months). In the hypothalamus, E or E + P but not P alone decreased postsynaptic 5-HT1A binding sites. In the dorsal raphe nucleus (DRN), E, P, and E + P treatments decreased 5-HT1A autoreceptor binding. The Kd values for 8-OH-DPAT were the same for each treatment group. Both the basal and the R-(+)-8-OH-DPAT stimulated [35S]GTP-γ-S binding were decreased during hormone replacement whereas the coupling efficiency between the receptor and G proteins was maintained. Finally, EE treatment reduced the level of Gαi3, but not Gαi1, Gαo, and Gαz in the DRN. In conclusion, these observations suggest that ovarian hormones may increase serotonin neurotransmission, in part, by decreasing 5-HT1A autoreceptors, 5-HT1A postsynaptic receptors, and the inhibitory G proteins for intracellular signal transduction.

    Original languageEnglish (US)
    Pages (from-to)12-24
    Number of pages13
    JournalNeuropsychopharmacology
    Volume27
    Issue number1
    DOIs
    StatePublished - 2002

    Fingerprint

    8-Hydroxy-2-(di-n-propylamino)tetralin
    Autoreceptors
    Receptor, Serotonin, 5-HT1A
    GTP-Binding Proteins
    Haplorhini
    Carrier Proteins
    Steroids
    Macaca
    Guanosine Triphosphate
    Synaptic Transmission
    Serotonin
    Hormones
    Protein Subunits
    Macaca mulatta
    Autoradiography
    Hypothalamus
    Horses
    Progesterone
    Estradiol
    Signal Transduction

    Keywords

    • Depression
    • Estrogen
    • Hormone replacement therapy
    • Primate
    • Progesterone
    • Serotonin

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys. / Lu, Nick Z.; Bethea, Cynthia.

    In: Neuropsychopharmacology, Vol. 27, No. 1, 2002, p. 12-24.

    Research output: Contribution to journalArticle

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