The role of basic fibroblast growth factor in the compensatory adrenal growth response
Basile, David Patrick
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https://hdl.handle.net/2142/22804
Description
Title
The role of basic fibroblast growth factor in the compensatory adrenal growth response
Author(s)
Basile, David Patrick
Issue Date
1994
Doctoral Committee Chair(s)
Holzwarth, Matilde
Department of Study
Molecular and Integrative Physiology
Discipline
Molecular and Integrative Physiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Animal Physiology
Language
eng
Abstract
We have investigated the role of basic fibroblast growth factor (bFGF) in the neurally mediated compensatory adrenal growth response. Unilateral adrenalectomy resulted in a 13%, 6% and 22% increase in adrenal weight, protein and DNA content, respectively, and 33-40% increases in the rate of cell proliferation measured by $\sp3\rm H$-thymidine incorporation in vitro. Three forms of bFGF, approximately 18.6, 21 and 22.5 kD were identified in rat adrenals by SDS-PAGE and Western blot. Basic FGF was localized immunocytochemically in cells of the glomerulosa and the medulla. Basic FGF stimulated a 68-80% increase in the rate of DNA synthesis in adrenal capsule-glomerulosa preps in vitro. Suramin (0.1 mM), a growth factor antagonist, blocked bFGF-receptor interaction in vitro and at 200 mg/kg given 5-7 days prior to adrenal surgery, blocked compensatory growth. Conversely, at 2.0 mg/kg, suramin significantly enhanced the compensatory growth response, perhaps caused by suramin-induced bFGF-receptor up-regulation as suramin-pretreatment also enhanced DNA synthesis in response to exogenous bFGF in vitro. Basic FGF receptors, with a $\rm K\sb{D}$ of 10 pM, were identified by binding analysis using primary cultures of rat glomerulosa cells, however, these results could not be demonstrated in capsule-glomerulosa tissue. Using autoradiography to verify the existence of bFGF receptors in vivo, heparin-insensitive $\rm\sp{125}I$-bFGF binding sites were concentrated primarily in the capsule and glomerulosa of the adrenal cortex suggesting the presence of FGF receptors. The presence of bFGF receptors was further verified by demonstration of internalization of $\rm\sp{125}I$-bFGF into cells of capsule-glomerulosa preps. This approach was used to demonstrate that suramin pretreatment of rats results in bFGF receptor up-regulation in the adrenal cortex. In addition we demonstrated a decrease in bFGF internalization in the remaining adrenal 24 hours after unilateral adrenalectomy suggesting the utilization of bFGF during the compensatory adrenal growth response. Together these data support the role for bFGF in autocrine stimulation of the adrenal cortex and in the compensatory adrenal growth response.
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