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Biomedical subjects

S M Cockle

Publications and source records attributed to S M Cockle.

At least 19 recordsLinked to original sources
PubMed2000

Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance.

The abrupt discontinuation of antidepressants can result in a syndrome of adverse events, including somatic, mood and psychomotor reactions. This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors (SSRIs) on cognitive and psychomotor function. Eighty-seven patients receiving maintenance therapy with fluoxetine, sertraline, paroxetine or citalopram had their treatment interrupted for 4-7 days using double-blind placebo. Assessments of aspects of cognitive and psychomotor performance, mood and symptoms were carried out at each visit. Following interruption of treatment, significant differences between the groups emerged. Paroxetine treated patients experienced significantly more cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003), compared to some or all of the other drugs. All changes were reversed on reinstatement of treatment. Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning, which may be related to the antidepressant discontinuation syndrome. These effects are not evident in patients receiving fluoxetine, sertraline and citalopram, suggesting they are not an SSRI class phenomenon.

Adult↗
PubMed1997

Fertilization-promoting peptide in reproductive tissues and semen of the male marmoset (Callithrix jacchus).

Fertilization-promoting peptide (FPP) is present in the prostate gland and semen of some mammals, and has been shown to enhance the fertilizing ability of both epididymal mouse and ejaculated human spermatozoa. The novel peptide may prove of importance for the treatment of some cases of male infertility, and a suitable animal model would be useful to test this hypothesis. To this end, we examined reproductive tissues and semen of the male marmoset for the presence of FPP. Peptides were extracted from seminal plasma, testes, prostate, and bulbourethral glands of intact and castrated male marmosets. The peptides were identified by ion-exchange chromatography followed by radioimmunoassay. The mean concentration of FPP immunoreactivity in semen from intact males was 58.7 nM (SE +/- 9.9 nM, n = 10), and anion-exchange chromatography revealed FPP as the only immunoreactive peptide present. Analysis of tissues revealed that FPP in semen was likely to be derived from the prostate gland, which contained this peptide as the major source of immunoreactivity (10.86 pmol/gland; SE +/- 4.39 pmol/gland, n = 4). Only low concentrations of FPP were detectable in the bulbourethral glands, and the peptide was undetectable in the testis. Surprisingly, FPP was readily detectable in the seminal plasma from one castrated marmoset and was present in the prostate gland from 3 castrates at levels which did not differ significantly from those in intact animals (5.47 pmol/gland, SE +/- 1.64 pmol/gland, n = 3). Plasma testosterone measurements indicated that residual circulatory androgens remained after castration, which may be consistent both with the maintenance of mating behavior and the presence of prostatic FPP. We conclude that FPP is present within the prostate gland and seminal plasma of the marmoset at concentrations consistent with a role in male fertility in this species.

Animals↗
PubMed1997

A fertilization promoting peptide (FPP)-related tripeptide competitively inhibits responses to FPP: a cause of male subfertility?

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2), a tripeptide structurally related to thyrotrophin releasing hormone (TRH; pGlu-His-ProNH2), is present in the prostate gland and seminal plasma of several mammalian species. FPP has been shown not only to stimulate the capacitation and fertilizing ability of epididymal mouse and ejaculated human spermatozoa, but also to inhibit spontaneous acrosome loss in mouse spermatozoa. These results suggest a possible role in vivo for FPP to maximize the fertilizing potential of the few cells that reach the ampulla. In this study we have investigated the effects of FPP-related peptides on mouse sperm capacitation and the acrosome reaction (using chlortetracycline fluorescence) and in vitro fertilizing ability. Deamidated FPP neither stimulated capacitation when tested at 50-200 nM nor interfered with FPP's stimulation of capacitation. Three neutral peptides (pGlu-Phe-ProNH2, MeO-FPP, pGlu-Gln-ProNH2) were also evaluated. pGlu-Phe-ProNH2, slightly stimulatory when used alone, had no additive effect when used in combination with FPP and the methyl derivative of FPP had no bioactivity itself and did not inhibit responses to FPP. In marked contrast, pGlu-Gln-ProNH2 (Gln-FPP), which had no bioactivity when added to uncapacitated suspensions at 50-100 nM, significantly inhibited FPP's stimulation of capacitation and fertilizing ability in vitro. Furthermore, when Gln-FPP + FPP were added to capacitated suspensions, Gln-FPP prevented FPP's inhibition of spontaneous acrosome loss. Our recent studies have indicated that FPP and adenosine can elicit similar responses but appear to act at different sites. The fact that Gln-FPP inhibited responses to FPP, but not to adenosine, indicates that Gln-FPP is acting at an FPP-specific site. We, therefore, conclude that the specific structure of the FPP molecule is crucial for biological activity. Removal of the terminal amide group abolishes bioactivity and changes to the central amino acid can have significant functional consequences. Since Gln-FPP is a candidate intermediate peptide in the FPP biosynthetic pathway and has been identified in human semen, abnormality in prostate function could lead to release of Gln-FPP along with, or instead of, FPP. Our results suggest that the relative proportions of FPP and related peptides in seminal plasma could have a significant effect on fertility in vivo.

Adenosine↗
PubMed1997

Urinary excretion of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in rats.

TRH-like immunoreactivity (TRH-LI) was estimated in methanolic extracts of rat tissues and blood by RIA using antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2, or antiserum 8880, which is specific for TRH (pGlu-His-ProNH2). TRH-LI (determined with antiserum 4319) and TRH (determined with antiserum 8880) contents were 8 and 8 ng/g in brain, 216 and 222 ng/g in hypothalamus, 6.5 and 6 ng/g in pancreas, 163 and 116 ng/g in male pituitary, 105 and 77 ng/g in female pituitary, 1 and 0.1 ng/g in salivary gland, 61 and 42 ng/g in thyroid, 12 and 3 ng/g in adrenal, 3 and 0.3 ng/g in prostate, and 11 and 0.8 ng/g in ovary respectively. Blood TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 31 and 18 pg/ml in male rats, and 23 and 10 pg/ml in female rats respectively. Unextracted serum obtained from blood kept for at least 1 h at room temperature no longer contained authentic TRH but still contained TRH-LI (males 20.3 +/- 3.1, females 15.9 +/- 3.0 pg/ml; means +/- S.E.M.). Isocratic reverse-phase HPLC showed that TRH-LI in serum is largely pGlu-Glu-ProNH2 (< EEP-NH2), a peptide previously found in prostate and anterior pituitary. In urine, TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 3.21 +/- 0.35 and 0.32 +/- 0.04 ng/ml in male rats and 3.75 +/- 0.22 and 0.37 +/- 0.04 ng/ml in female rats respectively (means +/- S.E.M.). Anion-exchange chromatography on QAE-Sephadex showed that urine of normally fed rats contains both basic/neutral TRH-LI (b/n TRH-LI) and acidic TRH-LI (aTRH-LI) in a ratio of approximately 40:60, and further analysis by HPLC indicated that aTRH-LI represents < EEP-NH2. Analysis of food extracts and urine from fasted rats demonstrated that b/n TRH-LI is derived from food particles spilled by the rats during urine collection, while aTRH-LI is endogenously produced. While urinary aTRH-LI levels were higher in female than in male rats (2.99 +/- 0.41 vs 2.04 +/- 0.20 ng/ml), the daily urinary excretion was similar in both sexes (females 15.6 +/- 1.4, males 19.5 +/- 2.0 ng/day). Intravenously injected < EEP-NH2 disappeared from serum with a half-life of approximately 1 h, and was recovered unchanged and quantitatively in urine. In contrast, when < EEP-NH2 was administered with food, only approximately 0.5% was recovered in urine. The urinary clearance rate of serum TRH-LI amounted to 0.52 +/- 0.10 ml/min in males and 0.34 +/- 0.05 ml/min in females. In view of the presence of < EEP-NH2 in the anterior pituitary gland, and the regulation of its content in parallel with gonadotrophins, we examined the possibility that serum < EEP-NH2 is of pituitary origin and correlates with gonadotrophin secretion. However, treatments that alter pituitary < EEP-NH2 content and gonadotrophin release had no effect on serum TRH-LI or urinary aTRH-LI. In conclusion, the TRH-like peptide < EEP-NH2 is present in rat serum and is excreted into the urine. Moreover, < EEP-NH2 in serum and urine is not derived from rat food and is probably not of pituitary origin.

Adrenal Glands↗
PubMed1996

A possible mechanism of action for fertilization promoting peptide, a TRH-related tripeptide that promotes capacitation and fertilizing ability in mammalian spermatozoa.

Fertilization promoting peptide (FPP), a tripeptide structurally related to thyrotrophin releasing hormone (TRH), has been shown to stimulate capacitation and fertilizing ability in both mouse and human spermatozoa, but the mechanisms of action involved in these responses are currently unknown. In the present study utilizing epididymal mouse spermatozoa, we have compared the ability of FPP, TRH, and pyroglutamylphenylalanineprolineamide (an uncharged structurally related tripeptide found in seminal plasma) to stimulate capacitation. At 50 nM, the mean concentration of FPP found in human seminal plasma, only FPP produced a significant response. This suggests that if a receptor is involved, it is one distinct from the TRH receptor. A significant response to FPP required the presence of extracellular Ca2+, with 90 microns Ca2+ being sufficient to support a stimulation of capacitation. The addition of FPP to suspensions at later stages of capacitation indicated that the nature of the response changed, such that addition of FPP to capacitated suspensions inhibited spontaneous acrosome reactions; however, FPP-treated cells were still able to undergo acrosomal exocytosis in response to progesterone, a physiological agonist of acrosomal exocytosis. Because earlier studies had identified a similar capacitation-related change in response to adenosine, being stimulatory early in capacitation and inhibitory later in capacitation, we investigated the possibility that FPP and adenosine might be acting via the same pathway. The combination of FPP plus adenosine, whether used at low, non-stimulatory concentrations or high, maximally-stimulatory concentrations, was more effective in promoting capacitation than either compound used individually. As observed with FPP, addition of adenosine to capacitated cells inhibited spontaneous acrosome loss but did not inhibit exocytosis in response to progesterone. This suggests that the two molecules are affecting a common pathway. Since adenosine, acting via specific cell surface receptors, can stimulate fertilizing ability and adenylate cyclase activity in uncapacitated cells and then inhibit enzyme activity in capacitated cells, we propose that FPP may act by modulating the adenylate cyclase/cyclic AMP signal transduction pathway. In vivo, FPP, which would contact spermatozoa at ejaculation and probably remain bound to cells for some time, could stimulate capacitation as the spermatozoa ascend the female tract; adenosine, present in seminal plasma and the female tract, could either augment FPP's action or replace it if FPP is lost from the cell surface. We therefore suggest that FPP and adenosine, by modulating adenylate cyclase activity to promote capacitation but inhibit spontaneous acrosomal exocytosis, may provide an endogenous mechanism that helps to optimize the fertilizing potential of the few sperm cells that reach the site of fertilization in vivo.

Animals↗
PubMed1996

Fertilization promoting peptide, a tripeptide similar to thyrotrophin-releasing hormone, stimulates the capacitation and fertilizing ability of human spermatozoa in vitro.

Recent studies have demonstrated that a prostatic tripeptide similar in structure to thyrotrophin-releasing hormone (TRH) can stimulate the in-vitro capacitation and fertilizing ability of epididymal mouse spermatozoa. Therefore we have proposed that this tripeptide be referred to as fertilization promoting peptide (FPP). Using chlortetracycline fluorescence analysis and the hamster oocyte penetration test (HOPT), we have obtained evidence that FPP can also promote the capacitation and fertilizing ability of ejaculated human spermatozoa in vitro. FPP (25-200 nM) caused a significant increase in the proportion of B-pattern uncapacitated cells, with no significant stimulation of acrosomal exocytosis. Comparison of FPP with two structurally similar tripeptides, TRH and pyroglutamyl phenylalanylprolineamide, at 50 nM revealed that only FPP could significantly promote capacitation. Finally, after a brief exposure to progesterone to induce acrosomal exocytosis in capacitated cells, FPP-treated suspensions penetrated a significantly higher proportion of oocytes than the untreated controls when assessed in the HOPT. The presence of FPP in human seminal plasma at concentrations similar to those used here suggests that, in vivo, FPP may play a positive role in promoting human sperm function.

Animals↗
PubMed1995

Peptides related to thyrotrophin-releasing hormone are degraded in seminal plasma by an enzyme similar to prolyl endopeptidase.

A TRH-like peptide, fertilization-promoting peptide (FPP), is present in high concentrations in mammalian prostate and semen and enhances the fertilization potential of spermatozoa. In this study, we have examined the properties of the enzyme that degrades TRH and FPP in rabbit seminal plasma. The enzyme responsible had a pH optimum of approximately 7.0, was inhibited by serine (di-isopropyl flurophosphate) and thiol (N-ethylmaleimide) protease inhibitors, bacitracin and concentrations of Zn2+ naturally present in seminal plasma: these functional reagents are all known to be potent inhibitors of prolyl endopeptidase. The major product after incubation of [3H]TRH in seminal plasma for 100 min was acid TRH (deamidated TRH) which is also the product after incubation of TRH with prolyl endopeptidase. Our results are consistent with the enzyme responsible for degradation of TRH and FPP in seminal plasma being similar to prolyl endopeptidase. The enzyme identified in this study is secreted and is therefore likely to be different from prolyl endopeptidase characterized from porcine brain, because the latter enzyme is known to be located in the cytosolic compartment of the cell.

Animals↗
PubMed1994

Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and semen.

The TRH-related peptide, pGlu-Glu-ProNH2, which was first identified in rabbit prostate has recently been named fertilization-promoting peptide (FPP) because of its ability to enhance the in vitro fertilizing potential of mouse epididymal spermatozoa. This study set out to examine the nature of the TRH-related peptides in human prostate and semen but, first, the optimal conditions for collection of semen samples were investigated. FPP was degraded slowly (t1/2 = 163 min, S.E. +/- 51.3, n = 6) in seminal plasma which has allowed us to measure accurately the concentrations of FPP, after extraction of the peptide in acidified acetone precisely 5 min after ejaculation. In this way, high levels of FPP (mean: 49.5 nmol/l) were detected in normal human semen, from young men, although other TRH-related peptides did not appear to be present. We have also examined the TRH-related peptides present in prostate samples from clinical patients both with and without evidence of benign prostatic hyperplasia (BPH), by ion-exchange chromatography followed by radioimmunoassay. Substantial concentrations of FPP were observed in normal (4.10 pmol/g tissue, S.E. +/- 1.46) and BPH prostate (6.27 pmol/g tissue, S.E. +/- 1.65). In addition, a second, neutral TRH-immunoreactive peptide was always detected in BPH tissue (7.40 pmol/g tissue, S.E. +/- 1.98) with only low levels generally present in normal prostate. The possibility that the presence of high levels of the neutral peptide in prostate may be used as an indicator of the onset of BPH deserves further scrutiny.

Adult↗
PubMed1994

Stimulating effect of pyroglutamylglutamylprolineamide, a prostatic, TRH-related tripeptide, on mouse sperm capacitation and fertilizing ability in vitro.

Pyroglutamylglutamylprolineamide, a prostatic tripeptide with structural similarities to thyrotrophin-releasing hormone (TRH), has been found in the seminal plasma of several mammalian species, suggestive of a biological function relating to spermatozoa. Using chlortetracycline (CTC) fluorescence analysis and in vitro fertilization, we have obtained evidence that the tripeptide stimulates mouse sperm capacitation and fertilizing ability in vitro. The tripeptide at concentrations from 5-500 nM was added to sperm suspensions and cells were assessed with CTC after 40 min, insufficient time for complete capacitation by a majority of spermatozoa under standard conditions of incubation. Concentrations of 25 nM and higher significantly promoted capacitation, as evidenced by a decrease in the proportion of acrosome-intact F pattern spermatozoa, characteristic of uncapacitated cells, and an increase in the proportion of acrosome-intact B pattern spermatozoa, characteristic of uncapacitated cells. However, there was no significant stimulation of acrosomal exocytosis. These results suggested that peptide-treated cells would be more fertile than their untreated counterparts. This was confirmed using in vitro fertilization, where the presence of 100 nM peptide during sperm preincubation and gamete coincubation significantly stimulated fertilizing ability (peptide, 56.5% of oocytes fertilized; controls, 26.5%). Comparison of the prostatic tripeptide and TRH effects on capacitation revealed that TRH at a concentration of 250 nM was as effective as the prostatic tripeptide in promoting the F-->B transition but was less effective or ineffective at lower concentrations. In vitro fertilization assessment of the two peptides, at 100 nM, revealed that only the prostatic tripeptide significantly stimulated fertility. Again, this was consistent with the CTC analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed1994

The effects of pyroglutamylglutamylprolineamide, a peptide related to thyrotrophin-releasing hormone, on rat anterior pituitary cells in culture.

Pyroglutamylglutamylprolineamide, which was first discovered in mammalian prostate, differs from thyrotrophin-releasing hormone (TRH) by substitution of glutamic acid for histidine at position two of the tripeptide. Recently, the newly discovered peptide has been identified in substantial concentrations in the rat anterior pituitary gland and, in this study, we have investigated the effects of the peptide on rat anterior pituitary cells in culture. GH3 cells were chosen to examine the possible effects of the new peptide, particularly in relation to its effects on the TRH receptor. This cell-type was deficient, in comparison with normal rat pituitary cells, in the new TRH-related peptide and appeared to be an ideal model cell in which to study the effects of pGlu-Glu-ProNH2. TRH (0.01-100 nM) was found to stimulate the secretion of both GH and prolactin from GH3 cells whereas pGlu-Glu-ProNH2 had no effect within the same concentration ranges. In contrast, at micromolar concentrations pGlu-Glu-ProNH2 exhibited intrinsic TRH-like activity causing stimulation of both GH and prolactin release from GH3 cells. Both TRH and pGlu-Glu-ProNH2 appeared to act through the same intracellular signalling mechanism, causing significant increases in intracellular inositol phosphate within the expected concentration ranges. However, pGlu-Glu-ProNH2 (up to 1 mM) displaced neither [3H]TRH nor [3H]MeTRH from membrane-binding sites on GH3 cells, suggesting that the effects of the new peptide were mediated through a second receptor. The physiological relevance of these effects of pGlu-Glu-ProNH2 requires further investigation.

Animals↗
PubMed1993

pGlutamylglutamylprolineamide modulation of growth hormone secretion in domestic fowl: antagonism of thyrotrophin-releasing hormone action?

Pyroglutamyglutamylprolineamide (pGlu-Glu-ProNH2) is a tripeptide with structural and immunological similarities to thyrotrophin-releasing hormone (TRH; pGlu-His-ProNH2). Since TRH stimulates GH secretion in domestic fowl, the possibility that pGlu-Glu-ProNH2 may also provoke GH release was investigated. Unlike TRH, pGlu-Glu-ProNH2 alone had no effect on GH release from incubated chicken pituitary glands and did not down-regulate pituitary TRH receptors. However, pGlu-Glu-ProNH2 suppressed TRH-induced GH release from pituitary glands incubated in vitro and competitively displaced [3H]methyl3-histidine2-TRH from pituitary membranes. Systemic injections of pGlu-Glu-ProNH2 had no significant effect on basal GH concentrations in conscious birds, but promptly lowered circulating GH levels in sodium-pentobarbitone anaesthetized fowl. Submaximal GH responses of conscious and anaesthetized birds to systemic TRH challenge were, however, potentiated by prior or concomitant administration of pGlu-Glu-ProNH2. These results demonstrate, for the first time, that pGlu-Glu-ProNH2 has biological activity, with inhibitory and stimulatory actions within the avian hypothalamo-pituitary axis. These results indicate that pGlu-Glu-ProNH2 may act as a TRH receptor antagonist within this axis.

Animals↗
PubMed1992

TRH-related peptides in the rabbit prostate complex during development.

The novel peptide, pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2), has recently been isolated and characterized from the rabbit prostate complex. The tripeptide is present in high concentrations in the prostate complex and semen, together with a 40-50 residue polypeptide which contains a TRH-immunoreactive fragment at its C-terminus. The present study investigates changes in the levels of these TRH-related peptides in rabbits aged 11 weeks, 4 months, 7 months, 13 months and 2 years. For each age group the peptides were extracted from the prostate complex, separated by gel exclusion chromatography, and located by TRH radioimmunoassay. The TRH-immunoreactive fragment was released from the polypeptide by trypsin digestion prior to radioimmunoassay. Very low concentrations of TRH-immunoreactive peptides were present at 11 weeks of age, but considerable levels of both peptides were found in all the other age groups. Anion exchange chromatography, under conditions which resolve TRH and pGlu-Glu-ProNH2, showed that the majority of the low molecular weight TRH immunoreactivity co-eluted with synthetic pGlu-Glu-ProNH2. The remaining TRH immunoreactivity, which had not bound to the anion resin, also failed to bind to a cation exchange column at pH 2.0, indicating that it was not authentic TRH. Dissection of the prostate complex into its four constitutive regions (vesicular gland, coagulating gland, prostate and bulbourethral gland) followed by extraction, chromatography and TRH radioimmunoassay of each region showed that the TRH-related peptides were located in the prostate.

Aging↗
PubMed1991

The TRH-like peptide pGlu-Glu-ProNH2 is present in the porcine pituitary but not in reproductive tissues.

The peptide pGlu-Glu-ProNH2, which differs from thyrotrophin-releasing hormone (TRH) by only one amino acid, was initially detected and characterised in the rabbit prostate complex and more recently in human semen and rat pituitary. A previous study reported that TRH and a homologous peptide were present in a range of porcine tissues and it was of interest to further characterise these peptides. In this study, high levels of TRH-immunoreactivity have been demonstrated in the porcine pituitary, the majority of which was authentic TRH; although 9% was found to be chromatographically identical to pGlu-Glu-ProNH2. In contrast, TRH-immunoreactivity was not detected in follicular fluid, ovary or prostate. The unexpected finding that pGlu-Glu-ProNH2 is present in the porcine pituitary but absent from regions of the reproductive tract may be of biological significance.

Aging↗
PubMed1991

Pyroglutamylglutamylprolineamide is present in rat anterior and posterior pituitary gland.

A new TRH-like peptide pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2) has recently been purified and characterized from both the rabbit prostate complex and human semen. In this study, TRH-immunoreactive peptides were extracted from anterior pituitary, posterior pituitary and hypothalamus and subjected to gel exclusion chromatography. For each tissue, TRH was resolved from pGlu-Glu-ProNH2 by anion-exchange chromatography at pH 7.6. In the anterior pituitary, 63% of the TRH immunoreactivity was chromatographically identical to pGlu-Glu-ProNH2 whereas in the posterior pituitary the new peptide represented less than 5% of the total TRH immunoreactivity. Only trace levels of pGlu-Glu-ProNH2 were observed in hypothalamus, suggesting that the acidic TRH-related peptide found in the anterior pituitary may not be of hypothalamic origin. The new TRH-like peptide was purified from whole pituitaries by gel exclusion and ion-exchange chromatography, followed by high power liguid chromatography and was shown to have chromatographic properties identical to pGlu-Glu-ProNH2. Amino acid analysis of the purified peptide revealed glutamic acid and proline residues in the ratio Glx:2 Pro:1, which is the expected composition of pGlu-Glu-ProNH2 after acid hydrolysis.

Animals↗
PubMed1990

TRH-extended peptides in the olfactory lobe are formed by incomplete cleavage at pairs of arginine residues in the TRH prohormone.

High concentrations of thyrotrophin-releasing hormone (TRH) are known to be present in the olfactory lobe, and the processing of the TRH prohormone in this region of the brain has been examined in this study. TRH-extended peptides have been detected in the rat olfactory lobe: these peptides accounted for approximately 11% of the total TRH immunoreactivity present in the tissue and contained the sequence pGlu-His-Pro-Gly-Arg exclusively at their N-termini. Extended peptides containing pGlu-His-Pro-Gly-Lys at their N-termini were not detected suggesting that incomplete cleavage occurs only at Arg-Arg residues in the TRH-prohormone. In view of the highly specific processing of the prohormone, it is likely that the TRH-extended peptides play important physiological roles.

Amino Acid Sequence↗
PubMed1989

The TRH-related peptide pyroglutamyglutamylprolinamide is present in human semen.

We have recently identified a novel peptide in the rabbit prostate complex which cross-reacts with an antibody to thyrotrophin-releasing hormone (TRH) and has the structure pGlu-Glu-ProNH2. In the present study, high concentrations of a TRH-related tripeptide and also a polypeptide (10-12 kDa) containing a TRH-immunoreactive peptide at its C-terminus were detected in human semen. The low molecular mass TRH-like peptide and the immunoreactive fragment from the polypeptide were isolated from human semen and shown to have identical structures. Amino acid analysis suggested compositions Glx2, Pro1, and after mild acid hydrolysis, the same sequence, Glu-Glu-Pro, was established for the two peptides. Fast atom bombardment (FAB) mass spectrometry yielded a pseudomolecular ion (M + H)+ of 355.38 which was identical to that of the synthetic peptide pGlu-Glu-ProNH2. The data demonstrate that human semen contains the TRH-like peptide pyroglutamylglutamylprolinamide and also a polypeptide terminating in the sequence Gln-Glu-ProNH2.

Adult↗