Specific Aim 1 will examine the electrophysiological basis of calcium oscillations in GnRH neurons, the effects of specific neurotransmitters on intracellular calcium and GnRH release, and the signaling pathways mediating these effects, and test the hypothesis that the synchronization of these calcium oscillations, which occur every 50 minutes, underlies the episodic secretion of GnRH.
Specific Aims 2 and 3 focus on the positive feedback actions of estradiol, using in vivo and in vitro approaches, respectively. The possible role of increased NPY and glutamate release and decreased GABA secretion in the initiation of the GnRH surge will be examined in vivo by determining the effects of estrogen treatment on levels of these neurotransmitters in the median eminence. The studies in Specific Aim 3 will test the hypothesis that estrogen acts directly on GnRH neurons in vitro to stimulate calcium oscillations and GnRH release or to alter their responsiveness to NPY, glutamate, or GABA.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD015433-20S1
Application #
6878439
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
De Paolo, Louis V
Project Start
1981-04-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
20
Fiscal Year
2004
Total Cost
$9,776
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
Kenealy, Brian P; Keen, Kim L; Garcia, James P et al. (2017) Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys. Proc Natl Acad Sci U S A 114:13804-13809
Kenealy, Brian P; Keen, Kim L; Garcia, James P et al. (2015) Prolonged infusion of estradiol benzoate into the stalk median eminence stimulates release of GnRH and kisspeptin in ovariectomized female rhesus macaques. Endocrinology 156:1804-14
Kurian, Joseph R; Keen, Kim L; Kenealy, Brian P et al. (2015) Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin-Releasing Hormone and Kisspeptin in Female Rhesus Monkeys. Endocrinology 156:2563-70
Joers, Valerie; Dilley, Kristine; Rahman, Shahrose et al. (2014) Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates. PLoS One 9:e104850
Alçin, E; Sahu, A; Ramaswamy, S et al. (2013) Ovarian regulation of kisspeptin neurones in the arcuate nucleus of the rhesus monkey (macaca mulatta). J Neuroendocrinol 25:488-96
Kenealy, Brian P; Kapoor, Amita; Guerriero, Kathryn A et al. (2013) Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin releasing hormone release. J Neurosci 33:19051-9
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
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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