The overall objective of this research project is to investigate the neurochemical mechanisms by which the ovarian hormones, estradiol (E2) and progesterone (P), exert their feedback controls over the secretion of luteinizing hormone (LH) from the anterior pituitary gland, and the overall hypothesis under investigations that the stimulatory and inhibitory effects of the ovarian hormones on the secretion of LH are mediated by changes in the activity of monoaminergic and peptidergic systems that regulate, directly or indirectly, the neurosecretion of LH-releasing hormone (LHRH) from the median eminence. This renewal application focusses on the interplay between the adrenergic neurotransmitters, norepinephrine (NE) and epinephrine (EPI), and neuropeptides, including endogenous opioids and neuropeptide Y, in mediating aspects of ovarian hormone positive feedback on LHRH and LH secretion in adult female rats, and secondly, on the effects exerted by gonadal hormones during the early neonatal period that influence the responsiveness of these neurotransmitter and neuropeptide systems to ovarian hormones in adulthood.
The specific aims of this proposal are first, to further investigate the interactions between the adrenergic neurotransmitters and NPY and between NPY and LHRH in mediating ovarian hormone positive feedback. These experiments will examine the involvement of adrenergic and NPY systems in inducing the changes in LHRH concentrations in the median eminence that precede the ovarian hormone- induced LH surge and in mediating the stimulatory effect of P on LHRH release in vitro. Additional studies will investigate the action of opioid and GABA systems to regulate NPY and adrenergic transmission controlling LHRH release, and will further characterize the mechanisms and the physiological significance of the facilitation by NPY of LHRH-induced LH release from anterior pituitary cells. The second specific aim is to examine whether ovarian hormones, and adrenergic, opioid and/or GABA systems influence the levels of NPY precursor mRNA in the medial basal hypothalamus. The third set of studies will more completely characterize the changes in adrenergic-peptidergic control over LHRH neurosecretion in rats defeminized by early exposure to E2, specifically by testing whether the neurochemical antecedents of the LH surge induced in normal females by ovarian hormones or antagonists at opioid or GABA receptors (i.e., accumulation of LHRH and NPY, activation of NE/EPI turnover) occur in feminized animals, but fail to occur in defeminized animals, of both sexes. The fourth specific aim is to investigate whether defeminization by neonatal exposure to E2 affects the development of the inhibitory EOP and GABAergic controls over the release of adrenergic transmitters and LHRH, and whether neonatal exposure to E2 with respect to ovarian hormone positive feedback mechanisms.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD013703-12
Application #
3312273
Study Section
Endocrinology Study Section (END)
Project Start
1979-12-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
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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