Submitted on September 12, 2006
Accepted on November 28, 2006
An Increase in In Vivo Release of LHRH and Precocious Puberty by Posterior Hypothalamic Lesions in Female Rhesus Monkeys (Macaca Mulatta)
Bret M Windsor-Engnell1, Etsuko Kasuya1, Masaharu Mizuno1, Kim Lee Keen1, and Ei Terasawa2*
1 Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, United States
2 Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, United States; Pediatrics, University of Wisconsin, Madison, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: terasawa{at}primate.wisc.edu.
We have previously shown that a decrease in GABA tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in 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 (17.5±0.1 months of age) received lesions in the PH, 3 prepubertal females (17.5±0.1 months) received sham lesions, and 2 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 (6:00-12:00 and 18:00-24:00) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty including significantly earlier menarche in PH lesion animals (18.9±0.2 months) than in sham/controls (25.5±0.6 months, 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, as evening GABA levels already deceased at 18-20 months of age in both groups and morning levels remain at the prepubertal levels. The age of first ovulation in both groups did not differ. Therefore, 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.
