Steroid inhibition of neural microvessel morphogenesis in vitro: receptor mediation and astroglial dependence.
Steroid hormones alter several aspects of microvascular 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 microvessel morphogenesis in vitro. C6 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 microM. Tetrahydrocortisone and 17 alpha-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.
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland.
J E
JE
Wolff
J
J
Laterra
G W
GW
Goldstein
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002196:Capillaries; D002454:Cell Differentiation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development; D005938:Glucocorticoids / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011980:Receptors, Progesterone / Q000378:metabolism; D011987:Receptors, Steroid / Q000502:physiology*; D012171:Retinal Vessels / Q000166:cytology / Q000254:growth & development*; D013256:Steroids / Q000494:pharmacology*
D005938:Glucocorticoids; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D013256:Steroids