Somatostatin desensitization in rat anterior pituitary cells

The possibility that desensitization to the inhibitory effects of somatostatin (SS) might develop following chronic exposure to this tetradecapeptide was examined in cultured rat anterior pituitary cells. Pretreatment with 1 microM SS for 48 h caused a shift in the IC50 of SS to inhibit 3-isobutyl-1-methylxanthine (IBMX) or growth hormone-releasing factor (GRF)-induced growth hormone (GH) and TRH + IBMX-induced thyroid-stimulating hormone (TSH) release by more than 2 orders of magnitude. Refractoriness developed after 12 h of exposure to doses of SS of 10 nM or more and became maximal at 48 h. Restoration of SS responsiveness followed a similar time-course upon removal of the peptide. In superfused cells, 10 nM SS lowered GH secretion rates to less than 5 ng/min within 2 h, but GH release began to rise after 16 h despite the continued presence of SS. However, when somatostatin was delivered in pulses, it remained fully effective for more than 36 h. Somatostatin-28 was also capable of inducing refractoriness in cultured pituitary cells. However, cells made refractory to either SS-14 or SS-28 were not made refractory to the same extent to the other form of somatostatin. These results indicate that the pituitary can become desensitized to the inhibitory actions of somatostatin just as it does to the stimulatory actions of the other hypothalamic releasing hormones.