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Am J Physiol Endocrinol Metab 292: E1000-E1009, 2007. First published December 5, 2006; doi:10.1152/ajpendo.00493.2006
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An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta)

Bret M. Windsor-Engnell,1 Etsuko Kasuya,1 Masaharu Mizuno,1 Kim L. Keen,1 and Ei Terasawa1,2

1Wisconsin National Primate Research Center and 2Department of Pediatrics, University of Wisconsin, Madison, Wisconsin

Submitted 12 September 2006 ; accepted in final form 28 November 2006

We have previously shown that a decrease in {gamma}-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 ± 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 ± 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600–1200 and 1800–2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 ± 0.2 mo) than in sham/controls (25.5 ± 0.9 mo, P < 0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18–20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.

timing of puberty; luteinizing hormone releasing hormone; lesions in the hypothalamus; primates



Address for reprint requests and other correspondence: E. Terasawa, Wisconsin National Primate Research Center, Univ. of Wisconsin, 1223 Capitol Court, Madison, WI 53715-1299 (e-mail: terasawa{at}primate.wisc.edu)







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