Facilitation or inhibition of the estradiol-induced gonadotropin surge in the immature rat by progesterone: Regulation of GnRH and LH messenger RNAs and activation of GnRH neurons

Barbara Attardi, Brian Klatt, Gloria E. Hoffman, M (Susan) Smith

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free α-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, α-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHβ, at 29 h. In the facilitation model, neither α-subunit nor LHβ mRNA increased with premature and enhanced release of LH and free α-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at ≃ 14.00 h and remained elevated until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P. In conclusion: 1) suppression of LH acid free α-subunit secretion by P can be accounted for at least partly by suppression of α-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.

    Original languageEnglish (US)
    Pages (from-to)589-599
    Number of pages11
    JournalJournal of Neuroendocrinology
    Volume9
    Issue number8
    StatePublished - Aug 1997

    Fingerprint

    Gonadotropins
    Gonadotropin-Releasing Hormone
    Progesterone
    Estradiol
    Neurons
    Messenger RNA
    Serum
    Secretory Component
    Ribonucleases
    Neuropeptides
    Northern Blotting
    Immunohistochemistry

    Keywords

    • α-subunit
    • cFos
    • GnRH
    • LH surge
    • Progesterone

    ASJC Scopus subject areas

    • Endocrinology
    • Neuroscience(all)

    Cite this

    Facilitation or inhibition of the estradiol-induced gonadotropin surge in the immature rat by progesterone : Regulation of GnRH and LH messenger RNAs and activation of GnRH neurons. / Attardi, Barbara; Klatt, Brian; Hoffman, Gloria E.; Smith, M (Susan).

    In: Journal of Neuroendocrinology, Vol. 9, No. 8, 08.1997, p. 589-599.

    Research output: Contribution to journalArticle

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    abstract = "We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free α-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, α-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHβ, at 29 h. In the facilitation model, neither α-subunit nor LHβ mRNA increased with premature and enhanced release of LH and free α-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at ≃ 14.00 h and remained elevated until at least 19.00 h. During this time 63-78{\%} of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P. In conclusion: 1) suppression of LH acid free α-subunit secretion by P can be accounted for at least partly by suppression of α-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.",
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