Alpha-adrenergic stimulation of growth hormone release in perifused rat anterior pituitary reaggregate cell cultures.
It has been previously shown that beta-adrenergic agonists stimulate growth hormone (GH) release from perifused rat anterior pituitary cell aggregates cultured in serum-free defined medium for 5-6 days. The present data show that the natural beta-agonist epinephrine (EPI) stimulates GH release through an additional alpha-adrenergic mechanism. The involvement of this mechanism was suggested by the following findings. The intrinsic activity of EPI, at concentrations greater than 10 nM, was significantly higher than that of isoproterenol (ISO) in stimulating GH release. Phenylephrine (PHE), a specific agonist of alpha 1-adrenergic receptors, provoked a significant rise of GH release. The effect was concentration dependent between 100 nM and 10 microM. The stimulatory effect of EPI and PHE was lowered, respectively blocked, by low concentrations of the potent alpha 1-adrenergic antagonist prazosin. The EPI-induced GH release could be totally blocked only by administration of both alpha- and beta-receptor antagonists. Under the same conditions and using concentrations up to 1 microM, the alpha 2-agonist clonidine had no or only a slight stimulatory effect; dopamine had no effect. Administration of both PHE and ISO resulted in a more than additive stimulation of GH release. The effectiveness of PHE but not clonidine, together with the high potency of the alpha 1-blocker prazosin suggest that the alpha-adrenergic receptor is predominantly of the alpha 1-subtype. When tested on days 1, 3, 6 and 8 in culture, both alpha- and beta-adrenergic responses appeared to be higher in the presence of the glucocorticoid dexamethasone compared to the responses in the absence of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
Maertens
P
P
Laboratory of Cell Pharmacology, University of Leuven, School of Medicine, Belgium.
Denef
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D013565:Sympatholytics; D010656:Phenylephrine; D003907:Dexamethasone; D013006:Growth Hormone; D007545:Isoproterenol; D002118:Calcium; D004837:Epinephrine