Degradation of Thyrotropin‐Releasing Hormone and Luteinising Hormone‐Releasing Hormone by Enzymes of Brain Tissue

O'cuinn, Gerard; O’Connor, Brendan; Elmore, Moira A.

doi:10.1111/j.1471-4159.1990.tb13276.x

Cited by 98 publications

(51 citation statements)

References 126 publications

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“…CAP and PAP-I were activated by DTT, a thiol-reducing agent, characterizing them as sulphydryldependent peptidases. DTT is an activator of the type I PAP and an inhibitor of the type II (O'Cuinn et al 1990), and the degradation of FPP (possible substrate of PAP-I) is also increased by the presence of DTT (Cockle et al 1994), which confirms that PAP-I is among the enzymes studied in the present work and FPP is one of its substrates. Overall, the present results show that seminal peptidase activities of C. d. terrificus have distinct biochemical properties, and therefore it is possible to attribute them to different proteins.…”

Section: Rattlesnake Seminal Peptidasessupporting

confidence: 66%

Peptidase activities in Crotalus durissus terrificus semen

Marinho

Almeida‐Santos²,

Carneiro³

et al. 2008

Reproduction

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To understand the role of peptidases in seminal physiology of Crotalus durissus terrificus, activity levels of representative enzymes in semen and their sensitivities to inhibitors, cofactors, and peptide hormones were evaluated. The existence of seminal fractions and the association of peptidases with these fractions were also characterized for the first time in snakes. The prominent inhibitors of aminopeptidases (APs) were amastatin for acid, basic, and neutral; bestatin for basic; and diprotin A for dipeptidyl-IV. Cystyl and prolylimino APs were similarly susceptible to the majority of these inhibitors. The basic and neutral were characterized as metallo-peptidases, acid AP was activated by MnCl 2 , and cystyl, prolyl-imino, and type I pyroglutamyl were characterized as sulphydryl-dependent APs. Angiotensin II, vasotocin, bradykinin, fertilization-promoting peptide, and TRH altered the majority of these peptidase activities; these peptides are possible substrates and/or modulators of these peptidases. Peptidase activities were found in all seminal fractions: seminal plasma (SP), prostasome-like (PR) structures, and soluble (S-) and membrane-bound fractions (MFs) of spermatozoa. The levels of activity of each peptidase varied among different seminal fractions. In SP, the higher activities were puromycin-insensitive neutral and basic APs. In PR, the higher activity was puromycin-insensitive neutral AP. In spermatozoa, the higher activity in subcellular SF was puromycinsensitive neutral, while in MF both puromycin-sensitive and -insensitive neutral APs were equally higher than the other examined peptidases. Data suggested that these peptidases, mainly basic and neutral, have a high relevance in regulating seminal functions of C. d. terrificus. Reproduction (2008) 136 767-776

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Section: Rattlesnake Seminal Peptidasessupporting

confidence: 66%

Peptidase activities in Crotalus durissus terrificus semen

Marinho

Almeida‐Santos²,

Carneiro³

et al. 2008

Reproduction

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“…3.4.19.3), the pyroglutamylhistidine bond. However, these soluble enzymes do not control intracellular TRH levels in vivo because TRH is stored inside secretory granules (O'Cuinn et al 1990, Joseph-Bravo et al 1998. A different pyroglutamyl peptidase was initially detected in serum and termed thyroliberinase because of its strict specificity for TRH (Bauer & Nowak 1979).…”

Section: Inactivationmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

Joseph‐Bravo

Jaimes-Hoy

Uribe

et al. 2015

Journal of Endocrinology

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This review presents the findings that led to the discovery of TRH and the understanding of the central mechanisms that control hypothalamus-pituitary-thyroid axis (HPT) activity. The earliest studies on thyroid physiology are now dated a century ago when basal metabolic rate was associated with thyroid status. It took over 50 years to identify the key elements involved in the HPT axis. Thyroid hormones (TH: T 4 and T 3 ) were characterized first, followed by the semi-purification of TSH whose later characterization paralleled that of TRH. Studies on the effects of TH became possible with the availability of synthetic hormones. DNA recombinant techniques permitted the identification of all the elements involved in the HPT axis, including their mode of regulation. Hypophysiotropic TRH neurons, which control the pituitary-thyroid axis, were identified among other hypothalamic neurons which express TRH. Three different deiodinases were recognized in various tissues, as well as their involvement in cell-specific modulation of T 3 concentration. The role of tanycytes in setting TRH levels due to the activity of deiodinase type 2 and the TRH-degrading ectoenzyme was unraveled. TH-feedback effects occur at different levels, including TRH and TSH synthesis and release, deiodinase activity, pituitary TRH-receptor and TRH degradation. The activity of TRH neurons is regulated by nutritional status through neurons of the arcuate nucleus, which sense metabolic signals such as circulating leptin levels. Trh expression and the HPT axis are activated by energy demanding situations, such as cold and exercise, whereas it is inhibited by negative energy balance situations such as fasting, inflammation or chronic stress. New approaches are being used to understand the activity of TRHergic neurons within metabolic circuits. A historical perspective on the hypothalamic control of the thyroid axisThe advancement of any scientific field requires the combination of creative new ideas with the development of technologies and knowledge in related areas; understanding the function of the hypothalamus-pituitarythyroid axis (HPT) is no exception (Figs 1 and 2). Since the end of the 19th century, European physicians and surgeons associated neck swelling (thyroid enlargement, goiter), with iodine deficiency, cretinism, and myxoedema, This paper is part of a thematic review section on 60 years of neuroendocrinology. The Guest Editors for this section were Ashley Grossman and Clive Coen defining hypothyroid conditions. Magnus-Levy (1895) was the first to demonstrate that respiratory metabolism was increased in hyperthyroidism and decreased in myxoedema. Indirect calorimetry allowed measurements of basal metabolic rate (BMR) and the evaluation of thyroid activity in clinical practice (Du Bois & Du Bois 1915, Harris & Benedict 1918. Soon it was recognized that stressful conditions such as fever, acidosis, or starvation modify BMR (Rowe 1920). In 1919, levothyroxine (3,3 0 ,5,5 0 -tetraiodothyronine or T 4 ) was characterized, and then ...

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“…All the TRH mediated metabolites other than unknown metabolite(s) were consistent with those reported previously. 2,11) Immunoblot Analysis Male F344/DuCrj rat liver, kidney and brain cytosolic or microsomal fractions and a polyclonal antibody raised against rat PAP-I in rabbits were prepared as previously described. 13) SDS-PAGE analysis of denatured samples (7-28 mg protein) was performed on 12.5% gels according to the method of Laemmli.…”

Section: )mentioning

confidence: 99%

“…1,11) Nevertheless, the contribution of cytosolic PAP-I to the hydrolysis of TRH in vivo is controversial. Charli et al 6) reported that pGlu diazomethyl ketone, a PAP-I inhibitor, did not enhance TRH levels in the brain in vivo or in vitro, but Faivre-Bauman et al 12) observed increased levels of TRH when primary cultures of hypothalamic cells were treated with Z-Gly-ProCHN 2 , also known as a PAP-I inhibitor.…”

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confidence: 99%

Marginal Involvement of Pyroglutamyl Aminopeptidase I in Metabolism of Thyrotropin-Releasing Hormone in Rat Brain

Abe

Fukuda

Tokui

2004

Biological & Pharmaceutical Bulletin

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Thyrotropin-releasing hormone (TRH) is a peptide hormone released from hypothalamic tissue and stimulates the release of thyroid-stimulating hormone (thyrotropin) from the mammalian anterior pituitary by binding to the TRH receptor on the cell surface of the pituitary.1,2) TRH is a tripeptide with the amino acid sequence L-pyroglutamyl-L-histidyl-L-prorineamide (L-pGlu-His-Pro-NH 2 ). The wide distribution of TRH throughout the central nervous system and the findings of various biochemical, pharmacological and behavioral studies strongly suggest that TRH likely acts as a neuromodulator/neurotransmitter in extrahypothalamic brain areas. 2,3)Current evidence strongly indicates that pyroglutamyl aminopeptidase II EC 3.4.19.6) is the principal enzyme responsible for terminating the actions of neuronally released TRH by removing the L-pGlu residue.4-6) PAP-II is a membrane-anchored zinc-metalloenzyme primarily located in the central nervous system and is known as a highly specific enzyme for TRH and very closely related compounds. 1,7)Pyroglutamyl aminopeptidase I (PAP-I, EC 3.4.19.3), a typical cytosolic cysteine peptidase, also can hydrolyze TRH as well as bioactive neuropeptides such as luliberin (LH-RH) and neurotensin due to its broad substrate specificity. [8][9][10] But the cytosolic peptidases are generally considered to have no role in the metabolism of these bioactive peptides, because neuropeptides are commonly hydrolyzed by ectoenzymes localized on the membrane of cells with the active site facing the extracellular space or by lysosomal peptidases after endocytosis.1,11) Nevertheless, the contribution of cytosolic PAP-I to the hydrolysis of TRH in vivo is controversial. Charli et al. 6) reported that pGlu diazomethyl ketone, a PAP-I inhibitor, did not enhance TRH levels in the brain in vivo or in vitro, but Faivre-Bauman et al. 12) observed increased levels of TRH when primary cultures of hypothalamic cells were treated with Z-Gly-ProCHN 2 , also known as a PAP-I inhibitor.Recently we expressed the functional forms of rat, mouse and human PAP-Is by Escherichia coli as a single protein and obtained an antibody raised against rat recombinant PAP-I. 13)Using these preparations, we showed that L-pGlu p-nitroanilide (L-pGlu-pNA) is a good non-peptide synthetic substrate for recombinant PAP-Is and is hydrolyzed solely by cytosolic PAP-I from the immunoprecipitation study using the antibody.13) We also demonstrated that the liver and kidney show relatively high PAP-I activities compared with other tissues tested.13) More recently we found that PAP-I is involved in the hydrolysis of some xenobiotic compounds having an LpGlu or L-pGlu-related structure, now under development in our company. 14,15) In this study, by using the recombinant PAP-Is and the antibody against rat PAP-I, we investigated the possible contribution of PAP-I to the degradation of TRH in rats based on biochemical experiments in brain subcellular fractions and immunohistochemical localization of PAP-I in the brain as well as the liver and kid...

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Degradation of Thyrotropin‐Releasing Hormone and Luteinising Hormone‐Releasing Hormone by Enzymes of Brain Tissue

Cited by 98 publications

References 126 publications

Peptidase activities in Crotalus durissus terrificus semen

Peptidase activities in Crotalus durissus terrificus semen

60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

Marginal Involvement of Pyroglutamyl Aminopeptidase I in Metabolism of Thyrotropin-Releasing Hormone in Rat Brain

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