Investigation of prolactin-related vasoinhibin in sera from patients with diabetic retinopathy.
نویسندگان
چکیده
OBJECTIVE In vitro experiments and in vivo studies on rodents demonstrate that N-terminal 14, 15, 16, 17, and 18 kDa fragments prolactin-related vasoinhibin (PRL-V) of human PRL are natural inhibitors of neovascularization in the retina and elsewhere. These N-terminal PRL fragments belong to a family of peptides named vasoinhibins, which act as endogenous regulators of angiogenesis and vascular function. These observations led to the hypothesis that PRL-V could play a role in the pathophysiology of diabetic retinopathy in humans. The purpose of this study was to investigate whether patients with diabetes mellitus and diabetic retinopathy have aberrant concentrations of PRL-V in the circulating blood. RESEARCH DESIGN We performed a case-control study and developed a new technique to semi-quantitatively determine PRL-V in serum samples from 48 male subjects. The case group consisted of 21 patients with diabetes mellitus and proliferative or non-proliferative diabetic retinopathy. The control group consisted of 27 healthy subjects with no history of diabetes mellitus. METHODS For the detection of PRL-V, we developed a new analytical method, consisting of immunologic and laser-induced fluorescence techniques. Results The case group had significantly lower PRL-V serum concentrations than the control group (P=0.041). There was no significant difference between patients with proliferative and those with non-proliferative diabetic retinopathy. CONCLUSION We conclude that given the antiangiogenic and antivasopermeability actions of PRL-V, the decreased serum levels of PRL-V in patients with diabetes mellitus could contribute to the development and progression of diabetic retinopathy.
منابع مشابه
Human Prolactin Point Mutations and Their Projected Effect on Vasoinhibin Generation and Vasoinhibin-Related Diseases
Background A dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL) has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in hum...
متن کاملFrom Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis
The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL) and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. V...
متن کاملVasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation.
Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retin...
متن کاملVasoinhibin gene transfer by adenoassociated virus type 2 protects against VEGF- and diabetes-induced retinal vasopermeability.
PURPOSE Specific proteolytic cleavages of the hormone prolactin (PRL) generate vasoinhibins, a family of peptides (including 16-kDa PRL) that are able to inhibit the pathologic increase in retinal vasopermeability (RVP) associated with diabetes. Here the authors tested the ability of an adenoassociated virus type 2 (AAV2) vasoinhibin vector to inhibit vascular endothelial growth factor (VEGF)- ...
متن کاملHigh Levels of Serum Prolactin Protect Against Diabetic Retinopathy by Increasing Ocular Vasoinhibins
OBJECTIVE Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sight-threatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men an...
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ورودعنوان ژورنال:
- European journal of endocrinology
دوره 161 2 شماره
صفحات -
تاریخ انتشار 2009