Decreased gonadotropin-releasing hormone neurosecretory response to glutamate agonists in middle-aged female rats on proestrus afternoon: a possible role in reproductive aging?
Before becoming acyclic, middle-aged rats display an attenuated LH surge and a decreased number of activated GnRH neurons. The present study examined whether the decreased activation of GnRH neurons in middle-aged rats could be due to defective glutamate neurosignaling in the hypothalamus. Arcuate nucleus/median eminence (ARC/ME) fragments were isolated from young (2-month-old) and middle-aged (9- to 11-month-old) rats at 1700 h on proestrus and incubated in vitro with or without the specific glutamate agonists, D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (1 mM), kainate (1 mM), and N-methyl-D-aspartate (NMDA; 50 mM). The results showed that basal GnRH release was similar in the two age groups. In contrast, stimulated GnRH release by D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCl stimulation at the end of the experiments confirmed the viability of all ARC/ME fragments. Quantitative reverse transcriptase-PCR revealed that messenger RNA levels for the major NMDA receptor subunit (NMDAR1) were significantly lower in the preoptic area and ARC/ME of the middle-aged rat on proestrus afternoon. As a whole, these findings suggest that a defect in hypothalamic glutamate neurosignaling may be an important mechanism leading to age-related defects in LH secretion and acyclicity in female animals.
Zuo
Z
Z
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912, USA.
Mahesh
V B
VB
Zamorano
P L
PL
Brann
D W
DW
D000375:Aging / Q000502:physiology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011359:Proestrus / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007986:Luteinizing Hormone; D007608:Kainic Acid