Abstract

This project will elucidate the mechanisms of TRH biosynthesis and regulation in the mammalian hypothalamic tuberoinfundibular system, a hormone which has important effects in the neuroendocrine control of anterior pituitary TSH and prolactin secretion. The sequence of rat preproTRH will be determined by isolating immuno-positive clones from a rat Lambdagtll expression library selected by antibody probes specific for proTRH. Based on the nucleotide sequence of the cDNA encoding preproTRH an antisense mRNA probe will be prepared complementary to TRH mRNA, using the Riboprobe vector for in situ hybridization histochemistry. The hybridization probes will be used to determine the effect of electrolytic ablation of specific afferent projections to TRH-containing neurons in the paraventricular nucleus and hormonal feedback, cold exposure and suckling on TRH biosynthesis using quantitative computer imaging and analysis. The delineation of the afferents to TRH-containing neurons and their specific peptidergic and aminergic mediators will be accompanied by anterograde tracing methods using the lectin PHA-L, combined with immunocytochemistry at the light and electron microscopic levels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037021-03
Application #
3235684
Study Section
Neurology C Study Section (NEUC)
Project Start
1986-02-01
Project End
1989-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Wittmann, Gábor; Szabon, Judit; Mohácsik, Petra et al. (2015) Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood-brain barrier of male rodents. Endocrinology 156:1552-64
Wittmann, Gábor; Harney, John W; Singru, Praful S et al. (2014) Inflammation-inducible type 2 deiodinase expression in the leptomeninges, choroid plexus, and at brain blood vessels in male rodents. Endocrinology 155:2009-19
Fekete, Csaba; Lechan, Ronald M (2014) Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev 35:159-94
Wittmann, Gabor; Hrabovszky, Erik; Lechan, Ronald M (2013) Distinct glutamatergic and GABAergic subsets of hypothalamic pro-opiomelanocortin neurons revealed by in situ hybridization in male rats and mice. J Comp Neurol 521:3287-302
Fekete, C; Zseli, G; Singru, P S et al. (2012) Activation of anorexigenic pro-opiomelanocortin neurones during refeeding is independent of vagal and brainstem inputs. J Neuroendocrinol 24:1423-31
Singru, Praful S; Wittmann, Gabor; Farkas, Erzsebet et al. (2012) Refeeding-activated glutamatergic neurons in the hypothalamic paraventricular nucleus (PVN) mediate effects of melanocortin signaling in the nucleus tractus solitarius (NTS). Endocrinology 153:3804-14
Marsili, Alessandro; Sanchez, Edith; Singru, Praful et al. (2011) Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase. J Endocrinol 211:73-8
Rosene, Matthew L; Wittmann, Gabor; Arrojo e Drigo, Rafael et al. (2010) Inhibition of the type 2 iodothyronine deiodinase underlies the elevated plasma TSH associated with amiodarone treatment. Endocrinology 151:5961-70
Sanchez, Edith; Singru, Praful S; Wittmann, Gabor et al. (2010) Contribution of TNF-alpha and nuclear factor-kappaB signaling to type 2 iodothyronine deiodinase activation in the mediobasal hypothalamus after lipopolysaccharide administration. Endocrinology 151:3827-35
Freitas, Beatriz C G; Gereben, Balazs; Castillo, Melany et al. (2010) Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest 120:2206-17

Showing the most recent 10 out of 59 publications