Our goal is to further elucidate the anatomical and neurochemical basis of gonadotropin secretion. Luteinizing hormone releasing hormone (LHRH) producing neurons play the primary role in gonadotropin secretion. However, LHRH neurons do not contain steroid receptors and, therefore, they are not direct targets of gonadal hormones. The feed-back effects of these hormones on LHRH release are mainly mediated by estrogen-sensitive neurons and circuits which are connected to the LHRH neurons. Experiments outlined in this proposal will further determine the location of the cells of origin of these afferent systems, including catecholamine and GABAergic neurons, as well as their inter- and afferent connections with other neuropeptide Y (NPY)- and beta-endorphin (beta-END)-containing neurons, which are known to play important roles in the regulation of LHRH neurons. The delineation of these connections will extend our understanding of the central regulation of gonadotropin hormone release and elucidate why, in different endocrine stages, the same transmitters can exert opposite effects on gonadotropin release. Furthermore, they will help to elucidate pathomechanisms of endocrine disease-and age-related malfunctions of the ovarian cycle. """"""""Classic"""""""" correlated light and electron microscopic techniques will be combined with state-of-the-art electron microscopic double immunostaining methods and antero-and retrograde tracer techniques. The proposed experiments will define: 1) What is the anatomical basis of the involvement of the estrogen- sensitive zona incerta in the regulation of LHRH release? 2) Which type(s) of catecholamine cells are involved in the beta-END- mediated control of LHRH release? 3) What are the locations and types of GABAergic systems involved in the direct and indirect control of gonadotropin release? 4) Which type(s) of NPY neurons are involved in the direct and indirect regulation of LHRH neurons? 5) What is the synaptological basis of interactions between beta-END and dopamine, and brain stem norepinephrine systems?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023830-07
Application #
2403166
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1989-09-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Leranth, C; Shanabrough, M (2001) Supramammillary area mediates subcortical estrogenic action on hippocampal synaptic plasticity. Exp Neurol 167:445-50
Leranth, C; Shanabrough, M; Horvath, T L (2000) Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 101:349-56
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
Leranth, C; Shanabrough, M; Horvath, T L (1999) Estrogen receptor-alpha in the raphe serotonergic and supramammillary area calretinin-containing neurons of the female rat. Exp Brain Res 128:417-20
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Horvath, T L; Naftolin, F; Leranth, C et al. (1996) Morphological and pharmacological evidence for neuropeptide Y-galanin interaction in the rat hypothalamus. Endocrinology 137:3069-78
Leranth, C; Kiss, J (1996) A population of supramammillary area calretinin neurons terminating on medial septal area cholinergic and lateral septal area calbindin-containing cells are aspartate/glutamatergic. J Neurosci 16:7699-710
Hof, P R; Glezer, I I; Revishchin, A V et al. (1995) Distribution of dopaminergic fibers and neurons in visual and auditory cortices of the harbor porpoise and pilot whale. Brain Res Bull 36:275-84

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