Delay of puberty and impairment of growth in female rats given a non competitive antagonist of NMDA receptors.
Reportedly, excitatory amino acids are involved in the control of gonadotropin secretion of rats and non-human primates. The aim of this study was to investigate the effect of chronic blockade of NMDA (N-methyl-D-aspartic acid) receptors by the non competitive receptor antagonist MK-801 on gonadotropin secretion and the onset of puberty in female rats. Moreover, since in humans alterations of the timing of puberty frequently coexist with disturbances of body growth, suggesting a common etiology for both events, we evaluated the effect of MK-801 also on the neural mechanisms controlling growth hormone (GH) secretion. Twenty-one-day-old female rats were treated with MK-801 (0.2 mg/kg ip, bid) or placebo for 10 days and were killed after 7 days of withdrawal. Administration of MK-801 induced a significant impairment of growth rate without altering food intake, and a delay in vaginal opening. Pituitaries from rats treated with MK-801 had a reduced luteinizing hormone (LH) content, and secreted in vitro lower amounts of LH both under basal and LHRH-stimulated conditions. MK-801 treated rats had a lower pituitary GH content and basal and GHRH-stimulated GH release and reduced plasma insulin-like growth factor-I levels. These data indicate that blockade of NMDA receptors in a critical period of the female rat life-span: 1) delays puberty by reducing gonadotropin secretion; 2) impairs growth rate by reducing GH secretion, with a mechanism still to be clarified.
Veneroni
O
O
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
Cocilovo
L
L
Müller
E E
EE
Cocchi
D
D
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007986:Luteinizing Hormone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012741:Sexual Maturation / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D016291:Dizocilpine Maleate; D007986:Luteinizing Hormone; D013006:Growth Hormone