Cellular mechanism of caprylic acid-induced growth hormone suppression

• Published in: Metabolism, clinical and experimental Vol. 39; no. 10; p. 1108
• Main Authors: Renier, G, Abribat, T, Brazeau, P, Deslauriers, N, Gaudreau, P
• Format: Journal Article
• Language: English
• Published: United States 01.10.1990
• Subjects: Animals; Caprylates - pharmacology; Cells, Cultured; Cyclic AMP - metabolism; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified - pharmacology; Growth Hormone - metabolism; Growth Hormone-Releasing Hormone - pharmacology; Male; Prolactin - metabolism; Rats; Rats, Inbred Strains; Receptors, Neuropeptide; Receptors, Neurotransmitter - drug effects; Receptors, Pituitary Hormone-Regulating Hormone
• ISSN: 0026-0495
• DOI: 10.1016/0026-0495(90)90173-A

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)NH2 (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 less than .05) and GRF-stimulated GH secretions (P less than .01), except when the maximal (near the EC100) 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, 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 Ca2+ 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 less than .05). In addition, the effect of caprylic acid on rGRF(1-29)NH2 affinity to GRF pituitary binding sites was determined using [125I-Tyr10]hGRF(1-44)NH2 as radioligand.