Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and semen. 752 75

Tcp-11 is a candidate for a distorter gene within the t-complex on mouse chromosome 17; although t-complex genes appear to affect sperm function, relatively little is known about mechanisms whereby these genes might play a specific physiological role. We present evidence that the protein TCP-11 is found on the surface of mature epididymal spermatozoa. Although detected on both the acrosomal cap region of the head and the flagellum of acrosome-intact cells, it is absent from the heads of acrosome-reacted cells. When epididymal spermatozoa were incubated in the presence of anti-TCP-11 IgG Fab fragments for a total of 120 min and assessed using chlortetracycline fluorescence, we observed a stimulation of capacitation and an inhibition of spontaneous acrosome loss, suggestive of enhanced fertility compared with untreated suspensions. In vitro fertilization experiments confirmed that Fab-treated suspensions became fertile more quickly and then maintained high fertility. Because these responses were remarkably similar to those obtained using the TRH-related peptide FPP (fertilization promoting peptide; pGlu-Glu-ProNH2) and adenosine, we investigated responses to Fab fragments, FPP, and adenosine. Results indicated that the Fab fragments appear to work at the same extracellular site as FPP, one that is distinct from the adenosine site of action. Further evidence for this conclusion was obtained using pGlu-Gln-ProNH2, an FPP-related tripeptide known to competitively inhibit responses to FPP; as with FPP, pGlu-Glu-ProNH2 inhibited the stimulatory effect of Fab fragments in a concentration-dependent manner. From these results we suggest that TCP-11 may be the receptor for FPP and that the adenylate clyclase/cyclic AMP pathway may be the signal transduction pathway activated by interactions between extracellular effector molecules (e.g., Fab fragments or FPP acting as an agonist) and TCP-11. A mechanism such as this that promotes capacitation but inhibits spontaneous acrosome loss in vivo would play a very important role by helping to maximize the fertilizing potential of the few spermatozoa that reach the site of fertilization. The fact that there is a human homolog of Tcp-11 suggests that this gene could play an important role in regulation of human, as well as mouse, sperm function.
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PMID:TCP-11, the product of a mouse t-complex gene, plays a role in stimulation of capacitation and inhibition of the spontaneous acrosome reaction. 932 50

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.
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PMID:A fertilization promoting peptide (FPP)-related tripeptide competitively inhibits responses to FPP: a cause of male subfertility? 936 48

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.
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PMID:Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism. 1049 13

Oxyntomodulin (OXM) is a product of proglucagon processing in the intestine and the central nervous system. We reported that intracerebroventricular (ICV) and intranuclear administration of OXM caused an inhibition of food intake in rats (Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, and Bloom SR. Endocrinology 142: 4244-4250, 2001). In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmol, for 7 days. A pair-fed control was included. These animals were restricted to the food intake of the OXM group but injected twice daily with saline. OXM-treated animals gained significantly less weight than either control group (day 8: OXM, 12.2 +/- 1.9 g vs. pair fed, 21.0 +/- 2.1 g; P < 0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13 +/- 0.03 g vs. pair fed, 1.29 +/- 0.04 g; P < 0.05) and interscapular brown adipose tissue (OXM, 0.15 +/- 0.01 g vs. pair fed, 0.18 +/- 0.01 g; P < 0.05) and increased core temperature compared with saline control, suggestive of enhanced energy expenditure. The food restriction-induced suppression in plasma TSH, seen in the pair-fed group, was prevented by OXM, potentially via increased release of hypothalamic TRH. In summary, ICV OXM causes reduced body weight gain and body adiposity following chronic administration.
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PMID:Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. 1238 65