Regulation of Blood Vessels by Prolactin and Vasoinhibins

Abstract

Prolactin (PRL) stimulates the growth of new blood vessels (angiogenesis) either directly through actions on endothelial cells or indirectly by upregulating proangiogenic factors like vascular endothelial growth factor (VEGF). Moreover, PRL acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects. In view of the opposing actions of PRL and vasoinhibins, the regulation of the proteases responsible for specific PRL cleavage represents an efficient mechanism for controlling blood vessel growth and function. This review briefly describes the vascular actions of PRL and vasoinhibins, and addresses how their interplay could help drive biological effects of PRL in the context of health and disease.

Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on blood-retinal barrier permeability: diabetic milieu makes a difference

“…We therefore tested this possibility and further postulated that vasoinhibins may regulate BRB permeability by blocking TRPV4. This novel concept is rooted in the fact that vasoinhibins exert effects opposite to the ones induced by TRPV4 activation to regulate capillary endothelial barrier (i.e., intracellular Ca 2+ rise, eNOS phosphorylation, NO release, cytoskeleton reorganization 36,43–46 ).…”

Remarks on the Prolactin Hypothesis of Peripartum Cardiomyopathy

“…The term “16 kDa PRL” (referring to prolactin as the precursor of the fragment) that has often been used in the PPCM-related literature was updated by the vasoinhibin nomenclature in 2006 (11, 12, 14), and this nomenclature has been refined and reevaluated since then (15–17). The introduction of the vasoinhibin nomenclature was triggered by the recognition that the 16-kDa fragment is not the only endogenous prolactin fragment with antiangiogenic properties.…”

“…Some of the cardiovascular side effects of bromocriptine such as syncope, hypotension, and pleural/pericardial effusion could be influenced by a decline of vasoinhibin levels. This is a possibility as vasoinhibins feature inhibition of vasodilation and vasopermeability (15, 16, 18). …”

“…Although dopamine agonists have been used during pregnancy, the safety of this intervention should carefully be monitored. This is particularly relevant on the background that vasoinhibins are pleiotropic hormones which control angiogenesis-mediated growth in reproductive and non-reproductive organs (18); regulate blood vessel growth, vasopermeability, and vasodilation (15, 16); and have non-vascular effects, which include stimulation of vasopressin release (20), thrombolytic effects (21), and the stimulation of anxiety- and depression-related behaviors (22). …”

Vasoinhibin Suppresses the Neurotrophic Effects of VEGF and NGF in Newborn Rat Primary Sensory Neurons

“…meability, and vasodilation [reviewed in [1][2][3] via a direct action on endothelial cells. The nature of the receptor(s) involved in these actions is unclear [4].…”