Abstract

This application will test the hypothesis that, in addition to its effects on neurotransmitter production and receptors, estrogen affects gonadotropin secretion in primates by regulating the synaptic connections between elements of the GnRH delivery system. The investigator proposes that by the time of the preovulatory gonadotropin surge, the ratio of the number of stimulatory and inhibitory synapses is higher on GnRH neurons than at any other time during the menstrual cycle. To test this hypothesis, the investigator will determine the synaptic connection and activity of GnRH neurons in the monkey brain during estrogen-regulated control of gonadotropins. During the project period, the investigator will study: 1) experimentally stimulated positive feedback induced by administered estradiol: 2) negative and positive feedback during the normal ovarian cycle; 3) feedback in normal males; 4) effects of ovariectomy with or without hormone replacement; and 5) naturally occurring menopause. Three major inhibitory and three major stimulator neurotransmitter systems will be studied in this project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS036111-04S1
Application #
6354479
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Kitt, Cheryl A
Project Start
1996-09-30
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$82,500
Indirect Cost

  Institution

Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Naftolin, Frederick; Malaspina, Dolores (2007) Estrogen, estrogen treatment and the post-reproductive woman's brain. Maturitas 57:23-6
Zsarnovszky, A; Horvath, T L; Garcia-Segura, L M et al. (2001) Oestrogen-induced changes in the synaptology of the monkey (Cercopithecus aethiops) arcuate nucleus during gonadotropin feedback. J Neuroendocrinol 13:22-8
Silva, I; Mor, G; Naftolin, F (2001) Estrogen and the aging brain. Maturitas 38:95-100; discussion 100-1
Zsarnovszky, A; Scalise, T J; Horvath, T L et al. (2000) Estrogen effects on tyrosine hydroxylase-immunoreactive cells in the ventral mesencephalon of the female rat: further evidence for the two cell hypothesis of dopamine function. Brain Res 868:363-6
Leranth, C; Roth, R H; Elsworth, J D et al. (2000) Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson's disease and memory. J Neurosci 20:8604-9
Diano, S; Urbanski, H F; Horvath, B et al. (2000) Mitochondrial uncoupling protein 2 (UCP2) in the nonhuman primate brain and pituitary. Endocrinology 141:4226-38
Diano, S; Naftolin, F; Goglia, F et al. (1998) Fasting-induced increase in type II iodothyronine deiodinase activity and messenger ribonucleic acid levels is not reversed by thyroxine in the rat hypothalamus. Endocrinology 139:2879-84
Horvath, T L (1998) An alternate pathway for visual signal integration into the hypothalamo-pituitary axis: retinorecipient intergeniculate neurons project to various regions of the hypothalamus and innervate neuroendocrine cells including those producing dopamine. J Neurosci 18:1546-58
Diano, S; Naftolin, F; Horvath, T L (1998) Kainate glutamate receptors (GluR5-7) in the rat arcuate nucleus: relationship to tanycytes, astrocytes, neurons and gonadal steroid receptors. J Neuroendocrinol 10:239-47
Diano, S; Naftolin, F; Goglia, F et al. (1998) Segregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone. Regul Pept 75-76:117-26

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