C-KIT LIGAND (STEM-CELL FACTOR) AFFECTS NEURONAL-ACTIVITY, STIMULATESPITUITARY-ADRENAL AXIS AND PROLACTIN SECRETION IN RATS

Stem Cell Factor (SCF) is a potent growth factor affecting proliferati on, differentiation and migration as well as secretory functions of va rious cells of different origin and function. The effect of SCF on neu ronal activity and on neuroendocrine regulation has been studied by in jecting SCF i.v. into conscious male rats. Administration of SCF eleva ted adrenocorticotropin (ACTH), corticosterone and prolactin (PRL) pla sma levels in a dose-dependent manner. Adrenocorticotropin and cortico sterone secretions were maximal after injecting 10 mu g SCF, while pro lactin secretion only reached a maximum at a dose of 20 mu g. Hormone secretions were maximal at 15 min (ACTH and PRL) or at 30 min (CORT) a nd declined to the baseline between 90 and 180 min. The functional ana tomical approach, using immediate-early gene product c-Fos as a marker of activated neurones, revealed that systemic administration of SCF a ctivated neurosecretory neurones of the hypothalamus in a time-depende nt manner. Somatosensory afferent pathways and extrahypothalamic areas - which are involved in the regulation of hypothalamic neurosecretory cells - including various parts of the lamina terminalis, bed nucleus of stria terminalis, central amygdala, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract and ventrolateral medulla also became Fos-positive. As SCF-induced mediators have been suggested to b e involved in brain pathophysiology, and as SCF might have be of poten tial therapeutic use in certain anaemias and leukaemias, the complex i nteraction between SCF-induced cell-specific actions and its effect on the neuroendocrine system should also be considered.