The Effects of Hypokalaemia on the Hormone Exocytosis in Adenohypophysis and Prolactinoma Cell Culture Model Systems

Abstract

The extracellular ion milieu determines the exocytosis mechanism that is coupled to spontaneous electrical activity. The K⁺ ion plays crucial role in this mechanism: as the potassium current is associated with membrane hyperpolarization and hormone release through protein cascade activation. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular K⁺ levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.

In our experimental study, female Wistar rats (n=20) were treated with estrone-acetate (150 μg/kg b.w./week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used to assess the apoptotic cells.

Differences between the effects of hypokalaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (p<0.001, n=10) in hormone exocytosis was detected in K⁺ treated adenohypophyseal and prolactinoma cell cultures compared to untreated groups. Immunocyto­chemistry showed that Bcl-2 expression was reduced under hypokalaemic conditions.

The decrease in hormone exocytosis was tightly correlated to the extracellular K⁺ in both cell types, leading to the conclusion that external K⁺ may be the major factor for the inhibition of hormone release. The significant increase in hormone content in supernatant media suggests that hypokalaemia may play important role in apoptosis.

Key words

adenohypophysis cell cultures - extracellular ion milieu - hypokalaemia - prolactinoma

• References

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