Based on previous work, the investigator proposes that a reduction in GABA tone is the critical change initiating puberty in rhesus monkeys and that this leads to subsequent establishment of facilitatory neuronal pathways. The first three Specific Aims will further test this hypothesis and examine possible molecular mechanisms underlying the change in GABA tone. The experiments in Specific Aim 1 will determine if blockade of GABA action leads to an increase in glutamate release in the median eminence and in the response to NMDA ,and monitor changes in glutamic acid decarboxylase (GAD) during puberty. GAD mRNA and protein levels will be measured using ribonuclease protection assay, in situ hybridization (ISH), and immunocytochemistry (ICC), and GAD bioactivity measured in vitro.
In Specific Aim 2, similar techniques will be use to examine expression of the GABA transporter (GAT-1) during puberty, and the importance of GAT-1 to control of LHRH will be tested by administration of an antagonist or antisense DNA.
In Aim 3, they will examine the possibility that changes in the subunit composition of the GABA receptor occur in the hypothalamus and, more specifically, in LHRH neurons using dual ICC an ISH.
Specific Aim 4 will test the hypothesis that a decrease in tonic inhibition by neuropeptide-Y (NPY) contributes to puberty by monitoring NPY mRNA and protein levels, determining if antisense DNA to NPY alters LHRH, GABA, or the response of LHRH neurons to NMDA, and if antisense DNA to GAD increases NPY.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD011355-19A2
Application #
6127027
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Grave, Gilman D
Project Start
1977-12-01
Project End
2005-04-30
Budget Start
2000-05-15
Budget End
2001-04-30
Support Year
19
Fiscal Year
2000
Total Cost
$226,968
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Kurian, Joseph R; Louis, Somaja; Keen, Kim L et al. (2016) The Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function. Endocrinology 157:3588-603
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Kurian, Joseph R; Terasawa, Ei (2013) Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne) 4:61
Terasawa, Ei; Guerriero, Kathryn A; Plant, Tony M (2013) Kisspeptin and puberty in mammals. Adv Exp Med Biol 784:253-73
Terasawa, Ei; Kurian, Joseph R; Keen, Kim L et al. (2012) Body weight impact on puberty: effects of high-calorie diet on puberty onset in female rhesus monkeys. Endocrinology 153:1696-705
Guerriero, Kathryn A; Keen, Kim L; Terasawa, Ei (2012) Developmental increase in kisspeptin-54 release in vivo is independent of the pubertal increase in estradiol in female rhesus monkeys (Macaca mulatta). Endocrinology 153:1887-97
Terasawa, Ei; Kenealy, Brian P (2012) Neuroestrogen, rapid action of estradiol, and GnRH neurons. Front Neuroendocrinol 33:364-75

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