Cellular mechanism of caprylic acid-induced growth hormone suppression

Abstract

To determine the dynamic secretory pattern of growth hormone (GH) in the presence of free fatty acids (FFA), we studied the effect of caprylic acid on basal and rGRF(1-29)NH 2 (GRF)-induced GH secretion in acutely dispersed and perifused rat pituitary cells. At a concentration of 3.0 mmol/L, caprylic acid inhibited both basal ( P < .05) and GRF-stimulated GH secretions ( P < .01), except when the maximal (near the EC 100) GRF concentration of 100 pmol/L was used. Lower concentrations of caprylic acid such as 0.3 and 1.0 mmol/L significantly inhibited, in a concentration-dependent manner, GH secretion induced by a 6.25-pmol/L GRF. However, at a GRF concentration of 25 pmol/L, this inhibitory effect was abolished. The time-course of GH response to GRF was similar in both control and caprylic acid-treated cells. To elucidate the mechanism(s) of action of the caprylic acid-induced blockade of GH secretion, we studied, in 3-day cultured rat pituitary cells, the effect of caprylic acid on basal and GRF-stimulated GH and 3′,5′-cyclic adenosine monophosphate (cAMP) release. We also tested its effect on the Ca 2+ ionophore, A23187-induced GH release. Caprylic acid (0.3 to 3.0 mmol/L) significantly inhibited basal GH release and GRF- or A23187-induced GH secretion. Furthermore, it decreased both basal and GRF-stimulated cAMP release ( P < .05). In addition, the effect of caprylic acid on rGRF(1-29)NH 2 affinity to GRF pituitary binding sites was determined using [ 125I-Tyr 10]hGRF(1-44)NH 2 as radioligand. This affinity was markedly diminished at 3 mmol/L caprylic acid, shifting IC 50 of competition curves performed with increasing rGRF(1-29)NH 2 concentrations (0 to 2.4 μmol/L) from 0.87 ± 0.14 nmol/L to 3.05 ± 0.65 nM ( P < .02). Finally, basal prolactin (PRL) secretion was not altered at a low caprylic acid concentration (0.3 mmol/L), while it was significantly decreased in the presence of 3.0 mmol/L caprylic acid ( P < .001). In summary, this study demonstrates that caprylic acid affects GH release by interfering with GRF receptors and altering adenylate cyclase-cAMP and calcium channel systems.