[Show abstract][Hide abstract] ABSTRACT: We examined the cross-regulation of signaling between ACTH-and platelet-activating factor (PAF)-mediated steroidogenesis in the perfused guinea pig adrenal gland. Our method of in situ perfusion using an artificial medium can evaluate whether cortisol secretion in response to ACTH and PAF is interactive. Treating adrenal glands with 100 pg/ml ACTH diminished the subsequent cortisol response to 10 nM PAF. By contrast, PAF resulted in subsequent potentiation of ACTH-induced cortisol secretion. A mixture of 50 microM L-alpha-1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of protein kinase C (PKC), and 3.3 microM calcium ionophore (A23187), or 10 microM forskolin (FRK) diminished the cortisol response to PAF, whereas that to ACTH was unaffected. Each of PAF, ACTH, or FRK eliminated the cortisol response to OAG plus A23187, whereas that to FRK was unaffected. These data show that the protein kinase A (PKA)-dependent processes activated by ACTH or FRK can interfere with PAF-induced signal transduction at receptor and post-receptor levels. In contrast, PKC-dependent processes activated by PAF promoted ACTH-signaling at receptor and post-receptor level. Cross-regulation between processes activated by PAF receptor-PKC and by ACTH receptor-PKA might function in the multifactorial regulation of adrenocortical steroidogenesis.
Journal of Endocrinology 11/2007; 195(1):29-38. DOI:10.1677/JOE-07-0251 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bilateral adrenals of the guinea pig were perfused in situ with an artificial medium equilibrated with 95% O2/5% CO2. Platelet-activating factor (PAF) induced biphasic cortisol responses, which reached a maximum at 10 nM PAF and declined at 100 nM. The effect of the PAF receptor antagonists CV-3988 and CV-6209 on PAF-stimulated cortisol secretion was examined. Prior exposure of adrenal glands to 10 microM CV-3988 or a simultaneous incubation with 10 microM CV-6209 abolished the cortisol response to 10 nM PAF. Lyso-PAF (a PAF precursor and breakdown product) did not affect cortisol secretion. Concentrations of 5-12.5 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a protein kinase C (PKC) inhibitor, abolished subsequent cortisol secretion in response to 10 nM PAF. N-[2-(Methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-8), a protein kinase A inhibitor, was less effective. A calcium ionophore (A23187) at 3.3 and 10 microM increased cortisol secretion, but the activator of PKC, l-alpha-1-oleoyl-2-acetyl-sn-3-glycerol (OAG), at 50 microM had no effect. When infused simultaneously, OAG (50 microM) and A23187 (3.3 microM) stimulated cortisol secretion synergistically. The secretory response of cortisol to repeated infusions of adrenocorticotrophin (100 pg/ml) or forskolin (10 microM) was essentially reproducible. By contrast, cortisol secretion in response to repeated infusions of PAF (10 nM) or OAG plus A23187 was not reproducible and the second response was diminished compared with the first. Our findings suggest that PAF plays a role in the regulation of steroidogenesis via a mechanism mediated by the PAF receptor and PKC.
Journal of Endocrinology 03/2005; 184(2):381-91. DOI:10.1677/joe.1.05937 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of SM12502 and CV6209, platelet-activating factor (PAF) receptor antagonists on corticosterone (B) secretion induced by ACTH was examined in the perfused adrenals of CD1 ICR (normal) and CD1 ICR nu/nu (athymic) mice. Bilateral adrenals were perfused in situ with an artificial medium equilibrated by 95% O2 + 5% CO2. Continuous infusion of 10 microM SM12502 or CV6209 inhibited the B response to 100 pg/ml ACTH markedly in normal mice but insignificantly in athymic mice. Infusion of PAF did not significantly affect B secretion in either normal or athymic mice. Administration of 0.1 microM of N-methylcarbamyl PAF, a nonmetabolizable PAF agonist, significantly increased B secretion in normal mice, but not in athymic mice. Infusion of SM12502 significantly depressed the B response to 10 microM forskolin or 1 mM dibutyryl cyclicAMP (cAMP) in normal mice, but not in athymic mice. The results indicate that endogenous PAF and its receptor may play a role in the ACTH-initiated signaling pathway at the phase after responsiveness to cAMP and its receptor may have little function in athymic mice.
Life Sciences 02/1998; 62(8):715-26. DOI:10.1016/S0024-3205(97)01170-3 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.