Evidence for the enzymic degradation of thyrotropin-releasing-hormone (trh) and pseudo-hormone (pyroglutamyl-histidyl-amphetamine) by calf liver pyroglutamine-amino-peptidase

Mokier, Elisabeth; Moreau, Odile; Masson, M.; Han, Kia‐Ki; Rips, Richard

doi:10.1016/0020-711x(79)90155-1

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…This enzyme is present in all life kingdoms, and found in many tissues, including brain. Although PPI hydrolyses TRH in vitro (Morier et al, 1979;O'Leary and O'Connor, 1995;Charli et al, 1998), the only evidence that it contributes to TRH turnover in situ is that an inhibitor of PPI (and PE) enhances TRH levels and release in primary cultures of hypothalamic cells (Faivre-Bauman et al, 1986). Since PPI action is probably restricted to the cytoplasm, it may contribute to the intracellular turnover of TRH leaking from intracellular granules, but its subcellular localization is not compatible with a post-secretory role.…”

Section: Introductionmentioning

confidence: 99%

The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?

et al. 2020

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Thyrotropin releasing hormone (TRH: Glp-His-Pro-NH 2) is a peptide mainly produced by brain neurons. In mammals, hypophysiotropic TRH neurons of the paraventricular nucleus of the hypothalamus integrate metabolic information and drive the secretion of thyrotropin from the anterior pituitary, and thus the activity of the thyroid axis. Other hypothalamic or extrahypothalamic TRH neurons have less understood functions although pharmacological studies have shown that TRH has multiple central effects, such as promoting arousal, anorexia and anxiolysis, as well as controlling gastric, cardiac and respiratory autonomic functions. Two G-protein-coupled TRH receptors (TRH-R1 and TRH-R2) transduce TRH effects in some mammals although humans lack TRH-R2. TRH effects are of short duration, in part because the peptide is hydrolyzed in blood and extracellular space by a M1 family metallopeptidase, the TRH-degrading ectoenzyme (TRH-DE), also called pyroglutamyl peptidase II. TRH-DE is enriched in various brain regions but is also expressed in peripheral tissues including the anterior pituitary and the liver, which secretes a soluble form into blood. Among the M1 metallopeptidases, TRH-DE is the only member with a very narrow specificity; its best characterized biological substrate is TRH, making it a target for the specific manipulation of TRH activity. Two other substrates of TRH-DE, Glp-Phe-Pro-NH 2 and Glp-Tyr-Pro-NH 2, are also present in many tissues. Analogs of TRH resistant to hydrolysis by TRH-DE have prolonged central efficiency. Structure-activity studies allowed the identification of residues critical for activity and specificity. Research with specific inhibitors has confirmed that TRH-DE controls TRH actions. TRH-DE expression by b2-tanycytes of the median eminence of the hypothalamus allows the control of TRH flux into the hypothalamus-pituitary portal vessels and may regulate serum thyrotropin secretion. In this review we describe the critical evidences that suggest that modification of TRH-DE activity in tanycytes, and/or in other brain regions, may generate beneficial consequences in some central and metabolic disorders and identify potential drawbacks and missing information needed to test these hypotheses.

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Section: Introductionmentioning

confidence: 99%

The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?

et al. 2020

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Enzymic inactivation of hypothalamic regulatory hormones

Griffiths

McDermott

1983

Molecular and Cellular Endocrinology

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Evidence for the enzymic degradation of TRH‐related pseudo‐peptides by porcine serum and brain homogenate

Morier

Han

Patsouris

et al. 1981

International Journal of Peptide and Protein Research

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Pseudo-peptides (pGlu-His-amphetamine, pGlu-His-Proamphetamine and pGluamphetamine) were subjected to enzymatic degradation by porcine serum and brain homogenate. The enzymic digests were (qualitatively) analyzed by the "Finger-prints" technique to provide evidence for the presence of free pyroglutamic acid and also quantitatively by HPLC to provide evidence for the presence and yield of free amphetamine. The stability in vitro toward enzymes of serum and brain homogenate of a new type of drug based on the combination of a peptide moiety (TRH) with a non peptide psycho-tropic moiety (amphetamine) is considered and discussed.

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Evidence for the enzymic degradation of thyrotropin-releasing-hormone (trh) and pseudo-hormone (pyroglutamyl-histidyl-amphetamine) by calf liver pyroglutamine-amino-peptidase

Cited by 3 publications

References 18 publications

The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?

The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?

Enzymic inactivation of hypothalamic regulatory hormones

Evidence for the enzymic degradation of TRH‐related pseudo‐peptides by porcine serum and brain homogenate

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