Steroid Inhibition of Neural Micro vessel Morphogenesis In Vitro: Receptor Mediation and Astroglial Dependence

Abstract: Steroid hormones alter several aspects of micro‐vascular function within the CNS. Both microvessel formation and blood‐brain barrier expression appear to be influenced by interactions between astrocytes and endothelial cells. To determine if steroids alter astrocyte‐endothelial interactions, we studied their effects on astroglial‐induced micro‐vessel morphogenesis in vitro. Q astroglial cells induce bovine retinal microvascular endothelial cells to differentiate into capillary‐like structures. Dexamethasone, hydrocortisone, and progesterone at 10 nM inhibited C₆‐induced microvessel morphogenesis by 75, 35, and 30%, respectively. Inhibition by dexamethasone was both time and concentration dependent, reaching 80‐100% at 1 μM. Tetrahydrocortisone and 17α‐hydroxyprogesterone had only marginal inhibitory effects. Cortexolone, a glucocorticoid receptor antagonist, blocked inhibition by dexamethasone. Progesterone receptors were expressed in C₆ but not bovine retinal microvascular endothelial cells, identifying the astroglial cell as the likely effector of progesterone‐mediated inhibition. Astroglial cells were further implicated as the effectors of steroid‐mediated inhibition because none of the steroids inhibited astroglial‐independent capillary‐like structure formation in response to a reconstituted extracellular matrix, Matrigel. These findings are evidence that steroids modulate neural microvascular endothelial cell functions indirectly through perivascular astrocytes via a receptor‐mediated mechanism.