The overall objective of this research program has been to identify and characterize the actions of the central neurotransmitter and neuropeptide systems that regulate the secretion of luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary gland in response to physiological stimuli. Studies conducted during the current funding period have demonstrated that one role of NPY in lactation is to amplify the inhibitory action of DA over PRL secretion, through a specific reduction in the entry of extracellular Ca2+ via L-type calcium channels. Because lactation is also characterized by a marked physiological hyperphagia, and because NPY is the most powerful central stimulant of feeding behavior, one set of proposed experiments will test the hypothesis that the NPY neurons of the arcuate nucleus also mediate the hyperphagia associated with lactation. Using a variety of approaches, the proposed experiments will investigate whether acute disruption of NPY transmission by central antiNPY immunoneutralization, antisense oligonucleotides or peptide antagonists of NPY decrease food intake during lactation and will test whether the Y1 and/or Y5 receptor mediates this action of NPY in lactation. A second major objective is to identify the physiological signal(s) responsible for the up-regulation of hypothalamic NPY during lactation. The proposed studies will test the hypothesis that the hypoinsulinemia associated with lactation increases the expression of NPY in the hypothalamus. These studies will test the effects of systemic insulin treatment of lactating rats on hypothalamic preproNPY mRNA levels, NPY peptide concentrations and NPY immunoreactivity, and will examine whether interruption of nursing, which reduces hypothalamic NPY expression, also alters circulating insulin concentrations. To test whether leptin might also be involved in the up-regulation of NPY in the arcuate-paraventricular-dorsomedial hypothalamic feeding network, a third set of studies will assess the effects of central leptin administration to lactating rats on hypothalamic pre proNPY mRNA levels, NPY tide concentrations and NPY immunoreactivity in the hypothalamus.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD013703-22
Application #
6387461
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
De Paolo, Louis V
Project Start
1979-12-01
Project End
2004-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
22
Fiscal Year
2001
Total Cost
$198,350
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Parker, Michael S; Balasubramaniam, Ambikaipakan; Sallee, Floyd R et al. (2018) The Expansion Segments of 28S Ribosomal RNA Extensively Match Human Messenger RNAs. Front Genet 9:66
Parker, Michael S; Park, Edwards A; Sallee, Floyd R et al. (2016) Canonical Matches of Human MicroRNAs with mRNAs: A Broad Matrix of Position and Size. Microrna 5:211-221
Parker, Michael S; Sallee, Floyd R; Park, Edwards A et al. (2015) Homoiterons and expansion in ribosomal RNAs. FEBS Open Bio 5:864-76
Parker, Michael S; Park, Edwards A; Sallee, Floyd R et al. (2015) G and C Iterons and Strings in MicroRNAs Should be Important in Regulation of mRNAs(†). Microrna 4:175-84
Parker, Michael S; Sah, Renu; Balasubramaniam, Ambikaipakan et al. (2014) On the expansion of ribosomal proteins and RNAs in eukaryotes. Amino Acids 46:1589-604
Parker, Michael S; Sah, Renu; Balasubramaniam, Ambikaipakan et al. (2014) Dimers of G-protein coupled receptors as versatile storage and response units. Int J Mol Sci 15:4856-77
Parker, Michael S; Balasubramaniam, Ambikaipakan; Parker, Steven L (2012) On the segregation of protein ionic residues by charge type. Amino Acids 43:2231-47
Parker, Michael S; Sah, Renu; Parker, Steven L (2012) Surface masking shapes the traffic of the neuropeptide Y Y2 receptor. Peptides 37:40-8
Parker, Michael S; Park, Edwards A; Sallee, Floyd R et al. (2011) Two intracellular helices of G-protein coupling receptors could generally support oligomerization and coupling with transducers. Amino Acids 40:261-8
Estes, Anne-Marie; McAllen, Kathleen; Parker, Michael S et al. (2011) Maintenance of Y receptor dimers in epithelial cells depends on interaction with G-protein heterotrimers. Amino Acids 40:371-80

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