IMMUNOSUPPRESSANT AGENT FK506 STIMULATES GROWTH-HORMONE (GH) SECRETION AND GENE-EXPRESSION OF HYPOTHALAMIC GH-RELEASING HORMONE IN THE RAT

Immunosuppressant agent FK506 has been reported to stimulate ACTH rele ase from pituitary cells. We examined the effects of FK506 on GH relea se from the rat anterior pituitary cells and the effects of FK506 on h ypothalamic GH-releasing hormone (GRH) and somatostatin (SS) gene expr ession in conscious male rats. In vitro experiments, the monolayer pit uitary culture and reverse hemolytic plaque assay were employed to exa mine the GH release from the rat anterior pituitary cells. In in vivo experiments, the FK506 was administered for 7 days and then sequential blood sampling was performed every 20 min during 6 h in conscious rat s. The hypothalamus was removed, and total RNA was extracted for North ern blot analysis. The FK506 significantly stimulated GK release from the rat anterior pituitary cells in a dose-dependent manner in vitro. In in vivo experiments, the area under the curve of GH surges was sign ificantly increased in FK506-treated rats, although the peak height an d the trough level of GK surges were not altered. Pituitary GH messeng er RNA (mRNA) levels were significantly increased by the FK506 treatme nt. Hypothalamic GRH mRNA levels were significantly increased in FK506 -treated rats, whereas hypothalamic SS mRNA levels were not altered. T hese findings indicate that FK506 stimulates GH secretion and gene exp ression of hypothalamic GRH in the rat.