FP04-6 Kisspeptin Mediates Neuroprogesterone Induction of the Luteinizing Hormone Surge

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP04-GnRH & Gonadotroph Biology & Signaling
Basic/Clinical
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:25 AM
Room 135 (Moscone Center)

Poster Board SAT-134
Lauren K Paaske*1, Paul E Micevych2 and Kevin Sinchak1
1California State University, Long Beach, Long Beach, CA, 2Davis Geffen Sch Med, Los Angeles, CA
Estradiol and progesterone are essential for ovulation to occur in the cycling female rat. The rapid rise of estradiol during positive feedback on the afternoon of proestrus stimulates the de novo synthesis of hypothalamic progesterone in astrocytes.  This neuroprogesterone is important for triggering the release of gonadotropin-releasing hormone (GnRH) causing the luteinizing hormone (LH) surge, resulting in ovulation. GnRH neurons in the diagonal band of Broca (DBB) that regulate the LH surge do not express progesterone receptors.  Therefore, neuroprogesterone must act on excitatory neuropathways or neurons that synapse on DBB GnRH neurons.  Kisspeptin neurons from the anteroventral periventricular nucleus (AVPV) region synapse on and activate DBB GnRH neurons to induce the LH surge.  Since kisspeptin neurons in this region express progesterone receptors, we hypothesized that estradiol-induced neuroprogesterone activates AVPV kisspeptin neurons, releasing kisspeptin to excite DBB GnRH neurons, triggering the LH surge. To demonstrate that kisspeptin release is downstream of neuroprogesterone synthesis in the LH surge neurosignaling pathway, progesterone synthesis was inhibited and kisspeptin was infused into the DBB to rescue the LH surge.  Ovariectomized (ovx) and adrenalectomized (adx) Long Evans rats were implanted with bilateral cannulae aimed at the DBB.  One week later (Day 0) animals were treated with either safflower oil or 50 μg EB (sc) at 1200 hours.  On Day 0 and Day 1 at 0800 hours, all animals received subcutaneous injections of the P450 side chain cleavage inhibitor, aminoglutethamide (AGT; 1 μg/0.1 ml) and on Day 2 all animals received 5 μg/0.1 ml AGT at 0800 hours.  On Day 2 a group of AGT/EB treated animals received progesterone (500 μg/0.1 ml sc; 1000 hours).  On Day 2, at approximately 1530 hours, all animals received DBB infusions of either saline or kisspeptin (10 μg/ul). At 1700 hours on Day 2 all animals were deeply anesthetized with isoflurane and killed by decapitation (53 hours post EB treatment).  Brains were collected for cannulae placement confirmation, and trunk blood was collected and serum was analyzed for LH levels by sandwich ELISA kit (Shibayagi, via BioVendor).  Inhibiting neuroprogesterone synthesis with AGT blocked EB induction of the LH surge.  Subsequent treatment of AGT/EB animals with either progesterone or DBB infusion of kisspeptin restored the LH surge compared to the either AGT/EB or AGT/oil saline infused animals (one way ANOVA df = 3,32; F=11.542; P<0.001; SNK P < 0.05).  These results are consistent with the idea that estradiol-induced neuroprogesterone induces the release of kisspeptin in the DBB triggering the LH surge in adx/ovx estradiol primed rats. Thus, kisspeptin appears to mediate neuroprogesterone induction of the LH surge.

Nothing to Disclose: LKP, PEM, KS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: National Institutes of Health (NIH) Grant HD042635 awarded to PEM
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