Regional distribution of the membrane-bound pyroglutamate amino peptidase-degrading thyrotropin-releasing hormone in rat brain

Vargas, Miguel; Méndez, Milagros; Cisneros, Miguel; Joseph‐Bravo, Patricia; Charli, Jean Louis

doi:10.1016/0304-3940(87)90450-2

Cited by 54 publications

(21 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The distribution of the activity of PPII in various brain regions was determined. Consistent with previous reports, frontal cortex activity was high, and ventral jpet.aspetjournals.org pons-medulla activity was low (Vargas et al, 1987). Medial septum and lateral septum activities were intermediate between these values (Fig.…”

Section: Resultssupporting

confidence: 92%

“…The intraperitoneal injection of PPII inhibitors does not change basal serum TSH levels, but it increases (or extends) TRH-or cold stressinduced serum TSH levels (Scalabrino et al, 2007;Sá nchez et al, 2009). Given that PPII activity is low in the anterior pituitary (Vargas et al, 1987), it is not expressed on thyrotrophs (Cruz et al, 2008), and it does not regulate TRH effect on TSH secretion from anterior pituitary cells (Cruz et al, 2008), PPII may have a minor role in the adenohypophysis for the control of TSH secretion. In contrast, PPII is expressed in the median eminence of the hypothalamus on ␤2 tanycytes, thus being able to inactivate TRH once released into the proximity of portal capillaries, and its inhibition enhances the recovery of TRH released in vitro from the median eminence (Sá nchez et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pyroglutamyl Peptidase II Inhibition Enhances the Analeptic Effect of Thyrotropin-Releasing Hormone in the Rat Medial Septum

Lazcano¹,

Uribe²,

Martínez-Chávez³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH 2 ) has multiple, but transient, homeostatic functions in the brain. It is hydrolyzed in vitro by pyroglutamyl peptidase II (PPII), a narrow specificity ectoenzyme with a preferential localization in the brain, but evidence that PPII controls TRH communication in the brain in vivo is scarce. We therefore studied in male Wistar rats the distribution of PPII mRNA in the septum and the consequence of PPII inhibition on the analeptic effect of TRH injected into the medial septum. Twelve to 14% of cell profiles expressed PPII mRNA in the medial septum-diagonal band of Broca; in this region the specific activity of PPII was relatively high. Twenty to 35% of PPII mRNA-labeled profiles were positive for TRH-receptor 1 (TRH-R1) mRNA. The intramedial septum injection of TRH reduced, in a dose-dependent manner, the duration of ethanol-induced loss of righting reflex (LORR). Injection of the PPII inhibitor pGlu-Asn-Pro-7-amido-4-methylcoumarin into the medial septum enhanced the effect of TRH. The injection of a phosphinic TRH analog, a higheraffinity inhibitor of PPII, diminished the duration of LORR by itself. In contrast, the intraseptal injection of pGlu-Asp-Pro-NH 2 , a peptide that did not inhibit PPII activity, or an inhibitor of prolyl oligopeptidase did not change the duration of LORR. We conclude that in the medial septum PPII activity may limit TRH action, presumably by reducing the concentration of TRH in the extracellular fluid around cells coexpressing PPII and TRH-R1.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Pyroglutamyl Peptidase II Inhibition Enhances the Analeptic Effect of Thyrotropin-Releasing Hormone in the Rat Medial Septum

Lazcano¹,

Uribe²,

Martínez-Chávez³

et al. 2012

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…This enzyme is located on adenohypophyseal cell membranes [4] and brain synaptosomal membranes [5, 6]. Pyroglutamyl peptidase II cleaves the pyroglutamyl-histidyl bond of TRH (pGlu-His-ProNH 2 ) but not the pyroglutamyl-histidyl bond of GnRH [7].…”

Section: Introductionmentioning

confidence: 99%

Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Lin

Wilk²

1998

Neuroendocrinology

View full text Add to dashboard Cite

The distribution of the mRNA of the specific thyrotropin-releasing-hormone (TRH)-degrading enzyme pyroglutamyl peptidase II (EC 3.4.19.6) in rat tissues and brain regions and its regulation in rat tissues and in GH3 cells was studied by a reliable and quantitative solution hybridization ribonuclease protection assay. The distribution of pyroglutamyl peptidase II mRNA levels was uneven with the highest level of mRNA found in brain. Within brain the distribution of pyroglutamyl peptidase II mRNA was heterogeneous. A single dose of T₃ markedly increased the level of pyroglutamyl peptidase II mRNA in the pituitary (p < 0.01) and in the liver (p < 0.05). In GH3 cells, exposure to T₃ at concentrations from 10^–10 to 10^–6M for time periods of 2–24 h, did not change pyroglutamyl peptidase II mRNA levels. Acute administration of TRH to rats had no effect on pyroglutamyl peptidase II mRNA levels. By contrast, TRH down-regulated pyroglutamyl peptidase II mRNA in GH3 cells. A similar effect was produced in GH3 cells by activators of protein kinase C. These studies reveal fundamental differences in the mechanism of regulation of pyroglutamyl peptidase II mRNA in pituitary and in GH3 cells. Elevation of pyroglutamyl peptidase II mRNA in liver by T₃ suggests that this organ is the source of the enzyme in serum.

show abstract

“…These effects may involve various hypothalamic targets because, for example, local injection of TRH into medial and lateral hypothalamus (LH) reduces feeding in rats (Suzuki et al 1982) whereas administration into the preoptic area, dorsomedial, or ventromedial hypothalamus (VMH) increases BAT temperature in hamsters (Shintani et al 2005). ISH of ppTRH mRNA, its receptors (TRH-R1 and TRH-R2), and inactivating enzyme (PPII) together with immunostaining of Trh and of TRH, as well as autoradiography of TRH binding sites, has been used to generate maps of brain TRHergic neurons, receptors, and inactivation sites (Vargas et al 1987, Hökfelt et al 1989, Lechan & Segerson 1989, Heuer et al 2000. However, the circuits in which they are involved are currently poorly understood as few of the projection fields of the TRH neurons have been identified with anterograde and retrograde techniques (Simmons & Swanson 2009, Wittmann et al 2009a,b, Fekete & Lechan 2014.…”

Section: Hypothalamic Trh Neuronal Populationsmentioning

confidence: 99%

Regulation of TRH neurons and energy homeostasis-related signals under stress

Joseph‐Bravo

Jaimes-Hoy

Charlí

2015

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription of Trh in vivo and in vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

show abstract

Regional distribution of the membrane-bound pyroglutamate amino peptidase-degrading thyrotropin-releasing hormone in rat brain

Cited by 54 publications

References 13 publications

Pyroglutamyl Peptidase II Inhibition Enhances the Analeptic Effect of Thyrotropin-Releasing Hormone in the Rat Medial Septum

Pyroglutamyl Peptidase II Inhibition Enhances the Analeptic Effect of Thyrotropin-Releasing Hormone in the Rat Medial Septum

Quantitation and Regulation of Pyroglutamyl Peptidase II Messenger RNA Levels in Rat Tissues and GH3 Cells

Regulation of TRH neurons and energy homeostasis-related signals under stress

Contact Info

Product

Resources

About