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Titolo:
Early prepubertal ontogeny of pulsatile gonadotropin-releasing hormone (GnRH) secretion: I. Inhibitory autofeedback control through prolyl endopeptidase degradation of GnRH
Autore:
Yamanaka, C; Lebrethon, MC; Vandersmissen, E; Gerard, A; Purnelle, G; Lemaitre, M; Wilk, S; Bourguignon, JP;
Indirizzi:
Univ Liege, Div Ambulatory Pediat & Adolescent Med, CHU Sart Tilman, Dev Neuroendocrinol Unit, B-4000 Liege, Belgium Univ Liege Liege Belgium B-4000 roendocrinol Unit, B-4000 Liege, Belgium Eurogentec, B-4000 Liege, Belgium Eurogentec Liege Belgium B-4000Eurogentec, B-4000 Liege, Belgium Mt Sinai Med Ctr, Dept Pharmacol, New York, NY 10029 USA Mt Sinai Med CtrNew York NY USA 10029 Pharmacol, New York, NY 10029 USA
Titolo Testata:
ENDOCRINOLOGY
fascicolo: 10, volume: 140, anno: 1999,
pagine: 4609 - 4615
SICI:
0013-7227(199910)140:10<4609:EPOOPG>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTORS; FOLLICLE-STIMULATING-HORMONE; RAT HYPOTHALAMIC EXPLANTS; LUTEINIZING-HORMONE; MEDIAN-EMINENCE; PEPTIDASE ACTIVITIES; OVARIECTOMIZED RATS; INVIVO DEGRADATION; PULSE-GENERATOR; LHRH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Bourguignon, JP Univ Liege, Div Ambulatory Pediat & Adolescent Med, CHU Sart Tilman, Dev Neuroendocrinol Unit, B-4000 Liege, Belgium Univ Liege Liege Belgium B-4000 t, B-4000 Liege, Belgium
Citazione:
C. Yamanaka et al., "Early prepubertal ontogeny of pulsatile gonadotropin-releasing hormone (GnRH) secretion: I. Inhibitory autofeedback control through prolyl endopeptidase degradation of GnRH", ENDOCRINOL, 140(10), 1999, pp. 4609-4615

Abstract

GnRH((1-5)), a subproduct resulting from degradation of GnRH by prolyl endopeptidase (PEP) and endopeptidase 24.15 (EP24.15) was known to account foran inhibitory autofeedback of GnRH secretion through an effect at the N-methyl-D-aspartate (NMDA) receptors. This study aimed at determining the possible role of such a mechanism in the early developmental changes in frequency of pulsatile GnRH secretion. Using retrochiasmatic explants from fetal male rats (day 20-21 of gestation), no GnRH pulses could be observed in vitro, whereas pulses occurred at a mean interval of 86 min from the day of birth onwards. This interval decreased steadily until day 25 (39 min), during the period preceding the onset of puberty. Based on GnRH((1-10)) or GnRH((1-9)) degradation and GnRH((1-5)) generation after incubation with hypothalamic extracts, EP24.15 activity did not change with age, whereas PEP activity was maximal at days 5-10 and decreased subsequently until day 50. These changes were consistent with the ontogenetic variations in PEP messenger RNAs (mRNAs) quantitated using RT-PCR. Using fetal explants, the NMDA-evoked release of GnRH was potentiated in a dose-dependent manner by bacitracin, a competitive PEP inhibitor and the desensitization to the NMDA effect was prevented using 2 mM of bacitracin. At day 5, a higher bacitracin concentration of 20 mM was required for a similar effect. Pulsatile GnRH secretion from fetal explants was not caused to occur using bacitracin or Fmoc-Prolyl-Pyrrolidine-2-nitrile (Fmoc-Pro-PyrrCN), a noncompetitive PEP inhibitor. At postnatal days 5 and 15, a significant acceleration of pulsatility was obtained using 1 mu M Of Fmoc-Pro-PyrrCN or 2 mM of bacitracin. At 25 and 50 days, a lower bacitracin concentration of 20 mu M was effective as well in increasing the frequency of GnRH pulsatility. We conclude that the GnRH inhibitory autofeedback resulting from degradation of the peptide is operational in the fetal hypothalamus but does not explain the absence of pulsatile GnRH secretion at that early age. After birth, PEP activity is high and may account for the low frequency of pulsatility. The potency of that effect decreases before the onset of puberty and may contribute to the acceleration ofGnRH pulsatility.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:18:23