engleski

Fickle adrenergic receptors in adrenal gland

Introduction: The adrenal gland is abundantly innervated, receiving its innervation primarily through the splanchnic nerve. Compensatory adrenal growth induced by unilateral adrenalectomy is a typical model for the investigation of neuroendocrine control of the gland. Classical experiments showed that this growth was markedly stimulated by adrenergic nerve fibres. Our goal was to identify the receptors and the underlying mechanisms involved in this phenomenon. Methodology: Female Wistar rats were used in all experiments. The first series comprised of in vivo pharmacological screening during compensatory growth, normal growth ( occuring between early post-natal and mature age) and stress-induced hypertrophy. The animals underwent a variety of pharmacological treatments: surgical sympathectomy ( splanchnicotomy), chemical sympathectomy (guaenethidine), treatment with adrenergic and dopaminenergic agonists/antagonists ; or various combinations of the mentioned. The second series were ex vivo experiments on adrenal cortices from unilaterally adrenalectomized and control animals. In one group of experiments, tissue concentrations of the main second messenger in beta-adrenergic signalling, cyclic AMP, were assessed. The second group were radiogland-binding experiments with [H]- DHA. The third series is currently being done on primary cultures of capsule-zona glomerulosa cells. Different procedures, including [H]-thymidine incorporation, measurement of cAMP levels and [H]- DHA binding, are used on cells obtained from either intact or unilaterally adrenalectomized animals undergoing various beta-adrenergic manipulations. Results and discussion: Based on the results of the in vivo innervation/receptor manipulations, we conclude that adrenergic stimulation of adrenal compensatory growth is mediated through beta-1 and beta-2 receptors. In contrast, neither normal nor stress-induced growth seem to be affected by adrenergic innervation and beta receptors, which suggests that beta-adrenergic stimulation is specific for compensatory growth after unilateral adrenalectomy. Ex vivo experiments showed that beta-adrenergic stimulation in adrenal cortices of unilaterally adrenalectomized animals paradoxically, and just in opposite to control tissue, induced a decrease and not increase in tissue cAMP concentration. Time-course experiments suggest that this change in beta-receptor signalling occurs between 2 hours and 2 days after surgery. At the same time, binding properties of [H]- DHA to cortical membrane preparations appear not to differ between control and compensating glands. Taken together, the presented dana suggest that unilateral adrenalectomy induces changes in beta receptors of the remaining gland- a change in physiological function (involvment in regulation of organ growth), a change in relationship to the main second messenger molecule (from stimulation to inhibition of adenylyl cyclase), with apparently no change in receptor number or affinity. Further investigations are needed to elucidate the nature of the receptor change and its link to regulation of adrenal growth.

adrenal gland; compensatory growth; beta receptor; signaling; cAMP

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