Endocrine Abstracts (2002) 3 P203

Neuropeptides and adrenocortical proliferation in vitro

EJ Whitworth1, JP Hinson1 & GP Vinson2

1Department of Molecular Endocrinology,Division of General and Developmental Medicine, Barts and The London, Queen Mary School of Medicine and Dentistry, London, UK; 2Department of Biological Sciences, Queen Mary, University of London, UK.

Vasoactive intestinal peptide (VIP) and Neuropeptide Y (NPY) are well established paracrine regulators of adrenal function. These neuropeptides have recently been immunolocalised to the capsule and zona glomerulosa region of the adrenal cortex, where they play a role in regulating steroidogenesis and adrenal blood flow. Neural mediation of compensatory adrenal growth following unilateral adrenalectomy and stimulation of proliferation and vascular hypertrophy in vascular smooth muscle cells (VSMC) by neuropeptides has been shown previously. This study was designed to investigate the effects of the adrenal neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) (both 10-6) on adrenocortical cellular proliferation and steriodogenesis in vitro. Capsular-glomerulosa preparations were cultured in vitro in eagles MEM (3.4mM K+) for 24hrs, 4 and 8 days and DNA synthesis as a marker of proliferative activity, was determined using FACS analysis, and immunocytochemistry through incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU, 20 mg/ml). Steroidogenic activity was accessed by aldosterone and corticosterone radioimmunoassay.

VIP (10-6) treatment significantly increased both aldosterone and corticosterone production after 24hrs and 4 days in culture (p<0.05). NPY (10-6) had no effect on corticosterone output from basal over this time, but interestingly decreased aldosterone production significantly from control (p<0.05). Niether neuropeptide had significant effect on steroid production after 8 days in culture. Nevertheless, both VIP and NPY caused a sustained increase in DNA synthesis compared to control within the subcapsular layer after 24hrs, 4 and 8 days in culture. These results suggests possible mitogenic role for neuropeptides in the adrenal.

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