1,721,495 research outputs found
The PDE5 Inhibitor Sildenafil Increases Circulating Endothelial Progenitor Cells and CXCR4 Expression
No full textINTRODUCTION:
Endothelial progenitor cells (EPC) are a specific subtype of progenitor cells that can be isolated from circulating mononuclear cells, able to migrate from the bone marrow to the peripheral circulation where they contribute to vascular repair. CXC-motif chemochine receptor 4 (CXCR4) receptor seems to play a critical role in this process.
AIM:
To assess the effects of sildenafil (a type 5 phosphodiesterase [PDE5] inhibitor) administration in 20 healthy young men.
METHODS:
Evaluation of CXCR4 expression in circulating EPC before and 4 hours after in vivo administration of 100 mg sildenafil by flow cytometry and colony-forming unit.
RESULTS:
We found that sildenafil increases circulating EPC number, the relative expression of CXCR4 on these cells and the ability to generate colonies in vitro.
CONCLUSIONS:
These data allow us to suppose an involvement of PDE5 in bone marrow release and peripheral homing of EPC
Lack of the T54A polymorphism of the DAZL gene in infertile Italian patients
No full textThe Thr54Ala polymorphism of the deleted-in-azoospermia-like (DAZL) protein has been associated with susceptibility to spermatogenic failure in the Taiwanese population. We used single-strand conformation polymorphism and restriction fragment analyses to investigate the presence of the A-->G transition in exon 3 of the DAZL gene in 95 infertile Italian patients. The patients had oligozoospermia or non-obstructive azoospermia with different degrees of testicular cytological picture. The allele carrying T54A polymorphism was not present in this group of patients nor in 63 controls, indicating that the frequency of this putative mutation is <1% in Italy. Since the Italian population usually shows allelic frequencies similar to the other Caucasian populations, we suggest that the T54A allele might play a role in infertility only in Taiwanese or Asiatic individuals
Y chromosome microdeletion in cryptorchidism and idiopathic infertility
No full textSettore ISI: Endocrinology and metabolism; I.F.: 5.44
Paracrine and endocrine roles of insulin-like factor 3
No full textInsulin-like factor 3 (INSL3) is expressed in Leydig cells of the testis and theca cells of the ovary. This peptide affects testicular descent by acting on gubernaculum via its specific receptor leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8). From initial animal data showing the cryptorchid phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in INSL3 and LGR8 genes was undertaken in human patients with cryptorchidism, and a frequency of mutation of 4-5% has been detected. However, definitive proofs of a causative role for some of these mutations are still lacking. More recent data suggest additional paracrine (in the testis and ovary) and endocrine actions of INSL3 in adults. INSL3 circulates at high concentrations in serum of adult males and its production is dependent on the differentiation effect of LH. Therefore, INSL3 is increasingly used as a specific marker of Leydig cell differentiation and function
Role of relaxin in human osteoclastogenesis.
No full textRecently, we have demonstrated that INSL3 is important for bone metabolism, and in this study we analyzed the possible role of the cognate hormone relaxin on human osteoclasts. In fact, previous studies showed an effect of relaxin on peripheral blood mononuclear cells (PBMCs), the precursors of osteoclasts. Analysis of the expression of the relaxin receptor RXFP1 and RLN-2 mRNA in primary cell cultures of human osteoclasts obtained from PBMCs showed by reverse transcriptase PCR and immunofluorescence only the presence of RXFP1 transcripts. Analysis of the in vitro effects of relaxin on osteoclastogenesis showed that relaxin is able alone to induce the differentiation of PBMCs into mature osteoclasts. This study shows, for the first time, that relaxin has an effect on bone metabolism, facilitating the differentiation of osteoclasts. A possible role for relaxin in osteolytic bone metastasis is also proposed
The great opportunity of the andrological patient: cardiovascular and metabolic risk assessment and prevention
No full textAndrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications
Diagnosing erectile dysfunction: flow-chart
No full textErectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%. A recent study reported an ED prevalence of 12.8% in Italy. ED is a symptom, sometimes the first, of different internal diseases. ED can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The andrologist's cultural baggage must include the ability to identify the pathology that can determine ED and the capacity to programme a specific diagnostic worku
Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A
No full textThe undercarboxylated form of osteocalcin (ucOC) regulates male fertility and energy metabolism,
acting through theGprotein-coupled receptor (GPRC)6A, thus forming anewpancreas-bone-testis
axis. Recently, GPRC6A has also been suggested to mediate the nongenomic responses of free
testosterone (T). However, these data did not consider the physiological scenario,wherecirculating
T is mainly bound to sex hormone-binding globulin (SHBG) and only a small percentage circulates
freely in the blood. Here, by the use of computational modelling, we document the existence of
similar structural moieties between ucOC and SHBG that are predicted to bind to GPRC6A at
docking analysis. This hypothesis of competition was assessed by binding experiments on human
embryonic kidney-293 cells transfected with human GPRC6A gene. Unliganded SHBG specifically
bound the membrane of human embryonic kidney-293 cells transfected with GPRC6A and was
displaced by ucOC when coincubated at 100-fold molar excess. Furthermore, specific downstream
Erk1/2 phosphorylation after stimulation of GPRC6A with ucOC was significantly blunted by 100-
fold molar excess of unliganded SHBG. Intriguingly previous incubation with unliganded SHBG,
followed by incubation with T, induced Erk1/2 phosphorylation in a dose-dependent manner.
Neither binding nor stimulating activities were shown for SHBG saturated with T. Experiments on
mutation constructs ofGPRC6Astrengthened the hypothesis of acommonbinding site ofucOCand
SHBG. Given the role of GPRC6A on energy metabolism, these data agree with epidemiological
association between SHBG levels and insulin sensitivity, suggest GPRC6A as a likely SHBG receptor,
and add bases for the possible regulation of androgen activity in a nonsteroidal manner
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