title: 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)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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Neuroendocrinology Laboratory, Notre-Dame Hospital Research Center, Montreal, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Renier
authors.forename: T
authors.initials: T
authors.lastname: Abribat
authors.forename: P
authors.initials: P
authors.lastname: Brazeau
authors.forename: N
authors.initials: N
authors.lastname: Deslauriers
authors.forename: P
authors.initials: P
authors.lastname: Gaudreau
mesh_terms: D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D008297:Male; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D018017:Receptors, Pituitary Hormone-Regulating Hormone
chemical_list: D002210:Caprylates; D005230:Fatty Acids, Nonesterified; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; C048250:somatotropin releasing hormone receptor; C031492:octanoic acid