The most advanced system for understanding neural and molecular mechanisms of mammalian behavior is the effect of estradiol (E) on lordosis behavior by the female rat upon mounting by the male. Now we must begin to understand signals from important environmental sources other than the male which are permissive for female reproductive behavior. Luckily, thyroid hormones (T3) and their receptors (TR-alpha and TR-beta) are present in hypothalamus and offer exciting opportunities for study. At the molecular level, TR s can bind on DNA to estrogen response elements (EREs) and could influence E-stimulated synthetic events in neurons. At the biological level, changes in thyroid hormone in the blood can signal environmental temperature changes as well as stress. Thus, we will study the ability of thyroid hormones to alter the stimulation of lordosis behavior by estradiol, we will determine where in the nervous system these interactions occur, and we will analyze their molecular mechanisms in the brain of the female rat. Precise sites of T3-TR action will be determined both by blocking- maneuvers (antisense DNA, etc.) And by direct T3 microinjections. The behaviorally relevant genes, for progesterone receptor (PR) and for the enkephalin peptides (PPE) will elucidated in this connection. In doing these experiments we have the chance of illuminating how permissive environmental conditions are integrated with the main hormal and sensory determinants of a biologically crucial behavior. Medically, high thyroid hormone levels are well known in the clinic to cause irritability in women. More generally, discovering in neurobiological detail how hormonal or environmental alterations quite separate from ovarian changes influence a female s reproductive status will be important for fostering women s health.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD005751-27
Application #
6181525
Study Section
Biopsychology Study Section (BPO)
Program Officer
De Paolo, Louis V
Project Start
1978-05-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
27
Fiscal Year
2000
Total Cost
$323,254
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
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Kow, Lee-Ming; Pfaff, Donald W (2016) Rapid estrogen actions on ion channels: A survey in search for mechanisms. Steroids 111:46-53
Ribeiro, Ana C; Ågmo, Anders; Musatov, Sergei et al. (2016) Silencing Estrogen Receptor-? with siRNA in the Intact Rodent Brain. Methods Mol Biol 1366:343-352
Faustino, Larissa C; Gagnidze, Khatuna; Ortiga-Carvalho, Tania M et al. (2015) Impact of Thyroid Hormones on Estrogen Receptor ?-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area. Neuroendocrinology 101:331-46
Chu, Xi; Gagnidze, Khatuna; Pfaff, Donald et al. (2015) Estrogens, androgens and generalized behavioral arousal in gonadectomized female and male C57BL/6 mice. Physiol Behav 147:255-63
Keenan, Daniel M; Quinkert, Amy W; Pfaff, Donald W (2015) Stochastic modeling of mouse motor activity under deep brain stimulation: the extraction of arousal information. PLoS Comput Biol 11:e1003883
Gore, Andrea C; Martien, Katherine M; Gagnidze, Khatuna et al. (2014) Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism. Endocr Rev 35:961-91
Davis, Elysia Poggi; Pfaff, Donald (2014) Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology 49:11-25
Gagnidze, K; Weil, Z M; Faustino, L C et al. (2013) Early histone modifications in the ventromedial hypothalamus and preoptic area following oestradiol administration. J Neuroendocrinol 25:939-55
Vasudevan, Nandini; Morgan, Maria; Pfaff, Donald et al. (2013) Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor ?1 or ? isoforms. Horm Behav 63:742-51

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