Abstract

The goal of this application is to understand the mechanisms controlling episodic release of LH and GnRH during the ovarian cycle, and to determine how these mechanisms are altered during seasonal anestrus in the ewe.
In Aim 1, fos and TH mRNA expression with A14/15 DA neurons will be used to examine activation of these cells by E2, and microdialysis will be used to examine DA release in the median eminence (ME).
Aim 2 will seek to identify the estrogen (E)-responsive cells that mediate the actions of E2 on DA neuronal activity using a variety of approaches.
Aim 3 will address mechanisms of action of progesterone (P) negative feedback during the luteal phase of the ovarian cycle, focusing on beta-endorphin and GABA as potential mediators.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017864-14
Application #
2872807
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
De Paolo, Louis V
Project Start
1983-09-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
West Virginia University
Department
Physiology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506

  Publications

Nestor, Casey C; Bedenbaugh, Michelle N; Hileman, Stanley M et al. (2018) Regulation of GnRH pulsatility in ewes. Reproduction 156:R83-R99
Weems, Peyton; Smith, Jeremy; Clarke, Iain J et al. (2017) Effects of Season and Estradiol on KNDy Neuron Peptides, Colocalization With D2 Dopamine Receptors, and Dopaminergic Inputs in the Ewe. Endocrinology 158:831-841
Grachev, P; Porter, K L; Coolen, L M et al. (2016) Surge-Like Luteinising Hormone Secretion Induced by Retrochiasmatic Area NK3R Activation is Mediated Primarily by Arcuate Kisspeptin Neurones in the Ewe. J Neuroendocrinol 28:
Fergani, Chrysanthi; Mazzella, Leanne; Coolen, Lique M et al. (2016) Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes? Endocrinology 157:4829-4841
Weems, Peyton W; Goodman, Robert L; Lehman, Michael N (2015) Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters. Front Neuroendocrinol 37:43-51
Goodman, Robert L; Coolen, Lique M; Lehman, Michael N (2014) A role for neurokinin B in pulsatile GnRH secretion in the ewe. Neuroendocrinology 99:18-32
Porter, K L; Hileman, S M; Hardy, S L et al. (2014) Neurokinin-3 receptor activation in the retrochiasmatic area is essential for the full pre-ovulatory luteinising hormone surge in ewes. J Neuroendocrinol 26:776-84
Goodman, Robert L; Hileman, Stanley M; Nestor, Casey C et al. (2013) Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control activity of the GnRH pulse generator in ewes. Endocrinology 154:4259-69
Nestor, Casey C; Coolen, Lique M; Nesselrod, Gail L et al. (2013) Evidence that orphanin FQ mediates progesterone negative feedback in the ewe. Endocrinology 154:4249-58
Merkley, Christina M; Porter, Katrina L; Coolen, Lique M et al. (2012) KNDy (kisspeptin/neurokinin B/dynorphin) neurons are activated during both pulsatile and surge secretion of LH in the ewe. Endocrinology 153:5406-14

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