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Department of Physiology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan

(Requests for offprints should be addressed to T Shimada; Email: tshimada{at}net.nagasaki-u.ac.jp)

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 µM CV-3988 or a simultaneous incubation with 10 µM 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 µM 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 µM increased cortisol secretion, but the activator of PKC, L--1-oleoyl-2-acetyl-sn-3-glycerol (OAG), at 50 µM had no effect. When infused simultaneously, OAG (50 µM) and A23187 (3.3 µM) stimulated cortisol secretion synergistically. The secretory response of cortisol to repeated infusions of adrenocortico-trophin (100 pg/ml) or forskolin (10 µM) 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.

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				T. Shimada, T. Hirose, I. Matsumoto, and T. Aikawa Cross-regulation of cortisol secretion by adrenocorticotropin and platelet-activating factor in perfused guinea pig adrenals J. Endocrinol., October 1, 2007; 195(1): 29 - 38. [Abstract] [Full Text] [PDF]