Mechanism of action of interleukin-1 beta in increasing corticotropin-releasing factor and adrenocorticotropin hormone release from cultured human placental cells.

The present study evaluated the possible effect and mechanism of action of interleukin-1 beta in regulating the release of corticotropin-releasing factor and adrenocorticotropin hormone from human cultured placental cells. With the use of a primary monolayer culture of human placental cells at term, the addition of interleukin-1 beta increased the release of immunoreactive corticotropin-releasing factor with a dose- and time-dependent effect. The intracellular concentration of both cyclic adenosine monophosphate and cyclic guanosine monophosphate increased in the presence of interleukin-1 beta. The addition of indomethacin, a prostaglandin synthesis inhibitor, partially reversed the effect of interleukin-1 beta. The same doses of interleukin-1 beta stimulated the release of adrenocorticotropin hormone and this effect was partially reversed by the addition of a synthetic corticotropin-releasing factor antagonist or by indomethacin. This study showed that interleukin-1 beta increases the release of corticotropin-releasing factor and adrenocorticotropin hormone from cultured placental cells. This effect is associated with increased intracellular cyclic nucleotide concentrations and is in part reversed by a prostaglandin synthesis inhibitor

Continuous subcutaneous growth hormone releasing factor analogue augments growth hormone secretion in normal male subjects with no desensitization of the somatotroph.

The effects of 8 day continuous subcutaneous (s.c.) infusions of growth hormone releasing hormone analogue (NLE27GRF(1-29)NH2 (GHRH.A)) on growth hormone (GH) secretion were studied in 14 normal adult male volunteers. GHRH.A was administered in doses which ranged from 7.5 to 120 ng/kg/min in doubling steps. Baseline GH profiles obtained during a 24 h infusion of normal saline in each subject were compared with profiles performed on days 1 and 8 of the infusion. Doses above 30 ng/kg/min augmented GH pulse amplitude and frequency. Doses of 60 ng/kg/min and 120 ng/kg/min appeared more satisfactory as these represented doses on the upwards slope of the dose response curve. However, at a dose of 120 ng/kg/min the GH secretion did not return to baseline for 12 of the 24 h. There was no evidence of desensitization or of depletion of the releasable GH pool with any dose. The possibility of treatment of short children with depot preparations of GHRH.A appears promising