The goal of the research is to further our understanding of the biochemical mechanisms underlying hormonal regulation of reproductive (estrous) behavior. This application focuses on the relationships between the biochemical and behavioral actions of estradiol (E2), an ovarian steroid that plays a pivotal role in the induction of female reproductive behavior. Since the hypothalamus (HYP) and preoptic area (POA) of the diencephalon have been identified as brain sites at which E2 acts to bring about estrous behavior, the proposed experiments investigate E2 action in the HYP-POA. This laboratory and others have provided correlative evidence that the interaction of E2 with high affinity binding proteins (receptors) in the HYP-POA is a prerequisite for the hormonal activation of female sexual behavior. The proposed research will begin to fill in the gaps in our knowledge of how E2 binding to receptors in neurons of the HYP-POA ultimately results in the expression of estrous behaviors many hours later. To accomplish this objective, the proposed studies will evaluate whether E2-induced conformational changes in the receptor protein and the subsequent binding of the hormone-receptor complex to chromatin material within HYP-POA cell nuclei are correlated with the induction of female reproductive behavior. Biochemical studies will define more precisely the molecular interactions between E2-receptor complexes and HYP-POA chromatin and will assess the role of these interactions in hormonal activation of estrous behavior. Additional experiments will examine E2 regulation of noradrenergic neurotransmission in vivo and in vitro to test the hypothesis that estrogen facilitation of noradrenergic activity in the HYP is involved in hormonal activation of reproductive behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH000636-03
Application #
3070023
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1986-09-15
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Ansonoff, M A; Etgen, A M (2001) Receptor phosphorylation mediates estradiol reduction of alpha2-adrenoceptor coupling to G protein in the hypothalamus of female rats. Endocrine 14:165-74
Acosta-Martinez, M; Fiber, J M; Brown, R D et al. (1999) Localization of alpha1B-adrenergic receptor in female rat brain regions involved in stress and neuroendocrine function. Neurochem Int 35:383-91
Etgen, A M; Chu, H P; Fiber, J M et al. (1999) Hormonal integration of neurochemical and sensory signals governing female reproductive behavior. Behav Brain Res 105:93-103
Fiber, J M; Etgen, A M (1998) Evidence that GABA augmentation of norepinephrine release is mediated by interneurons. Brain Res 790:329-33
Ansonoff, M A; Etgen, A M (1998) Estradiol elevates protein kinase C catalytic activity in the preoptic area of female rats. Endocrinology 139:3050-6
Karkanias, G B; Morales, J C; Etgen, A M (1998) Effects of diabetes and estradiol on norepinephrine release in female rat hypothalamus, preoptic area and cortex. Neuroendocrinology 68:30-6
Vathy, I; Sokol, J; Etgen, A M (1997) Gender-related differences exist in cortical [3H]nisoxetine binding and are not affected by prenatal morphine exposure. Neuroscience 76:331-4
Chu, H P; Etgen, A M (1997) A potential role of cyclic GMP in the regulation of lordosis behavior of female rats. Horm Behav 32:125-32
Karkanias, G B; Li, C S; Etgen, A M (1997) Estradiol reduction of alpha 2-adrenoceptor binding in female rat cortex is correlated with decreases in alpha 2A/D-adrenoceptor messenger RNA. Neuroscience 81:593-7
Fiber, J M; Etgen, A M (1997) GABA augments basal and electrically stimulated 3H-norepinephrine release in hypothalamic, preoptic area and cortical slices of female rats. Neurochem Int 31:769-80

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