Amino Acid Neurotransmission and Initiation of Puberty: Evidence from Nonketotic Hyperglycinemia in a Female Infant and Gonadotropin-Releasing Hormone Secretion by Rat Hypothalamic Explants
Amino Acids; Hypothalamus; Osmolar Concentration; Puberty; Synaptic Transmission; Time Factors
Abstract :
[en] The pulse frequency of hypothalamic GnRH secretion increases at the onset of puberty. In rodents and primates, this process involves facilitatory and inhibitory effects mediated through hypothalamic N-methyl-D-aspartic acid (NMDA) and gamma-aminobutyric acid (GABA) receptors, respectively. Precocious puberty was observed in an 11-month-old girl with nonketotic hyperglycinemia. This was thought to result from the effect of high concentrations of glycine (112 micromol/L in cerebrospinal fluid; normal, 3-12) acting on NMDA receptors as a coagonist of glutamate. Regression of pubertal development during anticonvulsive treatment with GABA agonists (loreclezole and vigabatrin) suggested that the stimulatory effects of glycine could be overcome by GABA receptor-mediated inhibition. These two hypotheses were tested in the in vitro model of the explanted hypothalamus from infantile (15-day-old) male rats. Glycine concentrations of 1-10 micromol/L increased the pulse frequency of GnRH secretion. This acceleration was prevented by 7-chlorokynurenic acid, a glycine antagonist at the NMDA receptor complex, and by the GABA agonist loreclezole. In addition, loreclezole and vigabatrin suppressed the developmental increase in the frequency of pulsatile GnRH secretion. The observation of precocious puberty in an infant with hyperglycinemia followed by pubertal regression during GABA agonist therapy and the in vitro findings in hypothalamic explants suggest that stimulatory inputs mediated through NMDA receptors and inhibitory inputs through GABA receptors are involved in the initiation of puberty.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Bourguignon, Jean-Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Jaeken, J.
Gerard, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Pédiatrie
de Zegher, F.
Language :
English
Title :
Amino Acid Neurotransmission and Initiation of Puberty: Evidence from Nonketotic Hyperglycinemia in a Female Infant and Gonadotropin-Releasing Hormone Secretion by Rat Hypothalamic Explants
Publication date :
1997
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Oxford University Press, New York, United States - New York
Volume :
82
Issue :
6
Pages :
1899-903
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Marion Merrell Dow Research Institute Janssen Pharmaceutica
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