scholarly journals C-type natriuretic peptide in reproduction, pregnancy and fetal development

2004 ◽  
Vol 180 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T Walther ◽  
H Stepan

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that consists of three structurally related peptides with a 17-amino acid ring linked by a disulfide bond. In contrast to atrial and brain natriuretic peptides that are mainly cardiovascular hormones, CNP acts predominantly in an autocrine/paracrine fashion, is commonly considered to be an endothelial hormone with antimitogenic properties, and is characterized as a regulator of endochondral ossification. Its biological effects are mediated by an intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B (GC-B) activation. There is growing evidence that this peptide is also involved in various reproductive processes as well as in embryonic and fetal development. In rodents, CNP and its receptor are highly expressed in the uterus and ovaries with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is detectable in mice embryos and shows an organ-specific expression in maternal reproductive tIssues with the highest concentration in the placenta. This could indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans, besides a postulated fetal de novo synthesis of CNP, both the peptide and its receptor are expressed in the placenta and myometrium with opposite regulation of CNP in pregnancies complicated by pre-eclampsia or intrauterine growth retardation. Since the maternal plasma levels do not reflect these alterations, one can conclude that this part of the natriuretic peptide system acts locally suggesting that CNP-stimulated cGMP release exhibits organ-specific effects. Importantly, CNP has also become a peptide with a distinct role in male reproductive processes, since endocrine function of the testis and the regulation of penile erection are regulated by the CNP/GC-B axis. This review gives a comprehensive overview of the multiple functions of CNP in reproduction and pregnancy as well as in embryonic and fetal development.

1996 ◽  
Vol 270 (6) ◽  
pp. R1324-R1331 ◽  
Author(s):  
C. J. Charles ◽  
E. A. Espiner ◽  
A. M. Richards ◽  
M. G. Nicholls ◽  
T. G. Yandle

Although atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) appear to share functional homology, there is doubt concerning a possible endocrine function for C-type natriuretic peptide (CNP) and the relative potency of species-specific forms of these hormones. Accordingly, we have examined the biological effects, interactions, and pharmacokinetics of equimolar doses (0.5 followed by 2.5 pmol.kg-1.min-1, each for 2 h) of species-specific forms of ANP, BNP-26, and CNP-22 in vehicle-controlled studies in normal conscious sheep. Although pharmacokinetics (metabolic clearance rates of 5.7 +/- 1.17, 7.5 +/- 1.36, and 4.7 +/- 0.71 l/min and half-lives of 3.9 +/- 0.42, 2.5 +/- 0.21, and 2.0 +/- 0.18 min for ANP, BNP, and CNP, respectively) are similar, the biological effects and actions on endogenous natriuretic peptide levels differ. Plasma BNP was significantly increased by CNP infusion (P < 0.0001), as was CNP by BNP infusions (P = 0.0009). Compared with ANP and BNP, which were equipotent in stimulating plasma guanosine 3',5'-cyclic monophosphate (cGMP; P < 0.0001 for both) and lowering arterial pressure (P < 0.05 for both) and cardiac output, CNP infusions induced only a small increment in cGMP and had no significant hemodynamic actions. In contrast, all three peptides suppressed plasma aldosterone levels (P < 0.05 for each), yet none induced significant natriuresis. Actions of CNP to increase BNP (and ANP) may account for the observed bioactivity of CNP. The findings show that potentially important interactions occur among all three hormones that need to be considered when interpreting the effects of individual peptides, particularly CNP.


1992 ◽  
Vol 40 (2) ◽  
pp. 283-291 ◽  
Author(s):  
S Mundlos ◽  
B Schwahn ◽  
T Reichert ◽  
B Zabel

We investigated the temporal and spatial distribution of osteonectin during human embryonic and fetal development, using in situ hybridization and immunohistochemistry. Osteonectin gene expression was generally found in cells exhibiting high rates of matrix production/proliferation. In mineralized tissue, a strong signal was obtained in osteoblasts, odontoblasts, and chondrocytes of the upper hypertrophic and proliferative zones. Chondrocytes of the mineralized zone showed no expression throughout the different stages of development. Strong osteonectin expression was found in odontoblasts of developing teeth. In addition, osteonectin mRNA and protein were detected in several non-mineralized tissues: steroid-producing cells of the adrenal gland and the gonads, kidney (glomeruli), lung (bronchi), skin, megacaryocytes, and large vessels. Histochemistry confirmed the results and detected extracellular osteonectin in bone and in the zone of mineralized cartilage only. The localization of osteonectin in bone, cartilage, and teeth is consistent with a role in the initiation of mineralization. However, the organ-specific distribution in non-mineralized tissues suggests an important multifunction role of this protein during human development.


Genome ◽  
2006 ◽  
Vol 49 (6) ◽  
pp. 619-630 ◽  
Author(s):  
T Nakazaki ◽  
T Tsukiyama ◽  
Y Okumoto ◽  
D Kageyama ◽  
K Naito ◽  
...  

Rice (Oryza sativa L.) pathogenesis-related (PR)-3 chitinases, like other PR proteins, are each coded by one of the genes of a multigene family in the plant genome. We assembled the database information about rice PR-3 chitinase sequences. A total of 12 PR-3 chitinase loci (Cht1 to Cht12) were found deployed in the rice genome. Some of the loci were occupied by 2 or more alleles. For all the loci expect Cht4, Cht5, Cht6, and Cht11, the amino acid sequence was polymorphic between japonica and indica varieties of rice, but glutamic acid acting as a catalytic residue was completely conserved in all the loci expect Cht7. All the genes except Cht7, which was not tested in this study, were transcripted in some organs (leaf, sheath, root, and meristem) of rice plants. These results suggest that chitinase proteins encoded by the genes at these loci have important biological effects, at least antifungal activities, on rice plants. We also proposed a new classification of rice PR-3 chitinases based on their domain structures. This classification was consistent with the results of phylogenetic analysis of rice chitinases.Key words: allelic relationship, classification, organ-specific expression, PR-3 chitinase, rice (Oryza sativa L.).


1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S315-S354 ◽  
Author(s):  
F. Neumann ◽  
R. von Berswordt-Wallrabe ◽  
W. Elger ◽  
K.-J. Gräf ◽  
S. H. Hasan ◽  
...  

ABSTRACT Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals. Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats. Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts: A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin. Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.


Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1465
Author(s):  
Ramon de Koning ◽  
Raphaël Kiekens ◽  
Mary Esther Muyoka Toili ◽  
Geert Angenon

Raffinose family oligosaccharides (RFO) play an important role in plants but are also considered to be antinutritional factors. A profound understanding of the galactinol and RFO biosynthetic gene families and the expression patterns of the individual genes is a prerequisite for the sustainable reduction of the RFO content in the seeds, without compromising normal plant development and functioning. In this paper, an overview of the annotation and genetic structure of all galactinol- and RFO biosynthesis genes is given for soybean and common bean. In common bean, three galactinol synthase genes, two raffinose synthase genes and one stachyose synthase gene were identified for the first time. To discover the expression patterns of these genes in different tissues, two expression atlases have been created through re-analysis of publicly available RNA-seq data. De novo expression analysis through an RNA-seq study during seed development of three varieties of common bean gave more insight into the expression patterns of these genes during the seed development. The results of the expression analysis suggest that different classes of galactinol- and RFO synthase genes have tissue-specific expression patterns in soybean and common bean. With the obtained knowledge, important galactinol- and RFO synthase genes that specifically play a key role in the accumulation of RFOs in the seeds are identified. These candidate genes may play a pivotal role in reducing the RFO content in the seeds of important legumes which could improve the nutritional quality of these beans and would solve the discomforts associated with their consumption.


2019 ◽  
Vol 31 (8) ◽  
pp. 1386 ◽  
Author(s):  
Fatma Uysal ◽  
Gokhan Akkoyunlu ◽  
Saffet Ozturk

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P&lt;0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P&lt;0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P&lt;0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.


1992 ◽  
Vol 70 (11) ◽  
pp. 1525-1528 ◽  
Author(s):  
D. A. Wigle ◽  
B. M. Bennett ◽  
D. B. Jennings ◽  
I. R. Sarda ◽  
T. G. Flynn ◽  
...  

Rat brain natriuretic peptide (rBNP) and iso-atrial natriuretic peptide (iso-rANP) were discovered independently by two research laboratories. They are considered to be members of the B-type natriuretic peptides. Except for the Gln/Leu substitution at position 44, the amino acid sequence of iso-rANP is identical with that of the C-terminal 45 amino acids of rat pro-BNP and with the 5-kDa cardiac peptide from rat atria. To determine whether this amino acid substitution can modify the known biological effects of rBNP and iso-rANP, the present investigation examined the cardiovascular and renal responses, vasorelaxant effect, receptor binding characteristics, and cyclic GMP production by the two peptides in relation to that of rat atrial natriuretic peptide (rANP). Results indicate that rBNP and iso-rANP are indistinguishable from each other in terms of these known biological activities of atrial natriuretic peptide. We therefore conclude that rBNP and iso-rANP are identical peptides and that the amino acid substitution at position 44 represents a polymorphic form of the rat B-type natriuretic peptide.Key words: atrial natriuretic peptide, brain natriuretic peptide, cardiovascular response, vasorelaxation, cyclic GMP, receptor binding.


1996 ◽  
Vol 81 (11) ◽  
pp. 3871-3876
Author(s):  
P J Hunt ◽  
E A Espiner ◽  
M G Nicholls ◽  
A M Richards ◽  
T G Yandle

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