Abstract

The long-term goal of this project is to elucidate the mechanisms controlling the occurrence of ovulatory cycles in female mammals. The working hypothesis to be tested is that anovulation during seasonal anestrus in the ewe is due to activation of inhibitory neural systems. Two such systems are proposed: a steroid-sensitive catecholaminergic system and a steroid-insensitive serotonergic system. One major specific aim of this project is to determine the anatomical location of these inhibitory neurons. This will be done using immunohistochemical staining, neurotransmitter receptor localization by in vitro incubation with 3H-ligand and autoradiography, knife cuts of specific neural tracts, and microinjection of neurotransmitter antagonists into specific hypothalamic areas. Experiments in the third specific aim will also make use of the lesioning techniques to test the possibility that one of these inhibitory neural systems activates the other.

  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 #
5R01HD017864-05
Application #
3314876
Study Section
Reproductive Biology Study Section (REB)
Project Start
1983-09-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
West Virginia University
Department
Type
School of Medicine & Dentistry
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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