Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion

C. Salas, M. Julio-Pieper, M. Valladares, R. Pommer, M. Vega, C. Mastronardi, B. Kerr, Sergio Ojeda, H. E. Lara, C. Romero

    Research output: Contribution to journalArticle

    57 Citations (Scopus)

    Abstract

    Context: Previous studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary. Objective: The objective of this study was to determine whether NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs. Patients and Interventions: Human GCs were obtained from in vitro fertilization patients and normal ovaries from women with elective pelvic surgery for nonovarian indications. Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor) were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in thecal cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E2) secretion and a reduction in progesterone output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by the trk tyrosine kinase blocker K-252a. Also, cells preexposed to NGF released significantly more E2 in response to hFSH than cells not pretreated with the neurotropin, showing that the NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs. Conclusions: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E 2 while preventing early luteinization via an inhibitory effect on progesterone secretion. NGF stimulates E2 secretion both directly and by increasing the formation of FSHRs.

    Original languageEnglish (US)
    Pages (from-to)2396-2403
    Number of pages8
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume91
    Issue number6
    DOIs
    StatePublished - 2006

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    trkA Receptor
    FSH Receptors
    Nerve Growth Factor
    Ovary
    Estrogens
    Chemical activation
    Progesterone
    Luteinization
    Human Follicle Stimulating Hormone
    Messenger RNA
    Granulosa Cells
    Fertilization in Vitro
    Gene expression
    Protein-Tyrosine Kinases
    Surgery

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion. / Salas, C.; Julio-Pieper, M.; Valladares, M.; Pommer, R.; Vega, M.; Mastronardi, C.; Kerr, B.; Ojeda, Sergio; Lara, H. E.; Romero, C.

    In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 6, 2006, p. 2396-2403.

    Research output: Contribution to journalArticle

    Salas, C. ; Julio-Pieper, M. ; Valladares, M. ; Pommer, R. ; Vega, M. ; Mastronardi, C. ; Kerr, B. ; Ojeda, Sergio ; Lara, H. E. ; Romero, C. / Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 6. pp. 2396-2403.
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    abstract = "Context: Previous studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary. Objective: The objective of this study was to determine whether NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs. Patients and Interventions: Human GCs were obtained from in vitro fertilization patients and normal ovaries from women with elective pelvic surgery for nonovarian indications. Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor) were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in thecal cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E2) secretion and a reduction in progesterone output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by the trk tyrosine kinase blocker K-252a. Also, cells preexposed to NGF released significantly more E2 in response to hFSH than cells not pretreated with the neurotropin, showing that the NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs. Conclusions: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E 2 while preventing early luteinization via an inhibitory effect on progesterone secretion. NGF stimulates E2 secretion both directly and by increasing the formation of FSHRs.",
    author = "C. Salas and M. Julio-Pieper and M. Valladares and R. Pommer and M. Vega and C. Mastronardi and B. Kerr and Sergio Ojeda and Lara, {H. E.} and C. Romero",
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    TY - JOUR

    T1 - Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion

    AU - Salas, C.

    AU - Julio-Pieper, M.

    AU - Valladares, M.

    AU - Pommer, R.

    AU - Vega, M.

    AU - Mastronardi, C.

    AU - Kerr, B.

    AU - Ojeda, Sergio

    AU - Lara, H. E.

    AU - Romero, C.

    PY - 2006

    Y1 - 2006

    N2 - Context: Previous studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary. Objective: The objective of this study was to determine whether NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs. Patients and Interventions: Human GCs were obtained from in vitro fertilization patients and normal ovaries from women with elective pelvic surgery for nonovarian indications. Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor) were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in thecal cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E2) secretion and a reduction in progesterone output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by the trk tyrosine kinase blocker K-252a. Also, cells preexposed to NGF released significantly more E2 in response to hFSH than cells not pretreated with the neurotropin, showing that the NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs. Conclusions: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E 2 while preventing early luteinization via an inhibitory effect on progesterone secretion. NGF stimulates E2 secretion both directly and by increasing the formation of FSHRs.

    AB - Context: Previous studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary. Objective: The objective of this study was to determine whether NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs. Patients and Interventions: Human GCs were obtained from in vitro fertilization patients and normal ovaries from women with elective pelvic surgery for nonovarian indications. Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor) were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in thecal cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E2) secretion and a reduction in progesterone output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by the trk tyrosine kinase blocker K-252a. Also, cells preexposed to NGF released significantly more E2 in response to hFSH than cells not pretreated with the neurotropin, showing that the NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs. Conclusions: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E 2 while preventing early luteinization via an inhibitory effect on progesterone secretion. NGF stimulates E2 secretion both directly and by increasing the formation of FSHRs.

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    U2 - 10.1210/jc.2005-1925

    DO - 10.1210/jc.2005-1925

    M3 - Article

    VL - 91

    SP - 2396

    EP - 2403

    JO - Journal of Clinical Endocrinology and Metabolism

    JF - Journal of Clinical Endocrinology and Metabolism

    SN - 0021-972X

    IS - 6

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