TY - JOUR
T1 - Decreased gonadotropin-releasing hormone neurosecretory response to glutamate agonists in middle-aged female rats on proestrus afternoon
T2 - A possible role in reproductive aging?
AU - Zuo, Zhuang
AU - Mahesh, Virendra B.
AU - Zamorano, Pedro L.
AU - Brann, Darrell W.
PY - 1996
Y1 - 1996
N2 - 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- α-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-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCI 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.
AB - 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- α-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-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and NMDA was significantly attenuated in middle-aged vs. young rats. KCI 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.
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U2 - 10.1210/endo.137.6.8641183
DO - 10.1210/endo.137.6.8641183
M3 - Article
C2 - 8641183
AN - SCOPUS:0029884761
SN - 0013-7227
VL - 137
SP - 2334
EP - 2338
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -