Calcium and growth hormone secretion in the domestic fowl (Gallus domesticus)

Extracellular calcium is a ubiquitous molecule required for secretagogue induced growth hormone release from somatotroph cells of the chicken anterior pituitary. Growth hormone release can be induced via different intracellular pathways and these in turn can act to produce a synergistic hormone release. This thesis sought to further characterise the intracellular and membrane dependent pathways involved in growth hormone release with regard to the regulation of calcium ion and other ion fluxes, and to determine the mechanism for GRF and TRH synergy in the domestic fowl. Growth hormone secretion from chicken somatotroph cells was dependent upon the extracellular calcium concentration and its subsequent influx into dispersed chicken somatotroph cells in vitro, which was blocked by voltage dependent calcium channel antagonists. Both parameters also demonstrated a dependence on extracellular sodium. TRH stimulated growth hormone release was similarly dependent on the influx of calcium from the extracellular space in dispersed chicken somatotroph cells in vitro. hpGRF-44/TRH synergy, however, failed to show a corresponding potentiated calcium influx with the synergistic growth hormone release - this response was merely additive with respect to the two secretagogues. The intracellular second messenger dbc-AMP produced similar responses, in the presence of the various modulatory agents, to those observed with hpGRF-44, although the maximal levels reached were lower. hpGRF-44 depolarised chicken somatotroph cells in vitro. The profile of changes in the membrane potential indicated the presence of sodium, calcium and potassium channels. Removal of extracellular sodium abolished hpGRF-44 induced depolarisation. Low and high extracellular calcium concentrations resulted in potentiated and reduced responses respectively. Repolarisation of the somatotroph cells was dependent on calcium and although none of the calcium dependent potassium channel antagonists affected the maximal depolarisation that was reached, apamin removed the ability of the cells to repolarisc and thus depolarisation was prolonged. In the presence of these agents an enhanced release of growth hormone was observed under conditions of a prolonged depolarisation whilst it was diminished when the depolarisation was shortened or abolished. It is therefore concluded that hpGRF-44 induced growth hormone release in chickens is dependent on the influx of extracellular calcium which in turn is dependent on a variety of mechanisms not least the voltage dependent calcium channels. Ion fluxes are also modulated via a hpGRF-44 induced depolarisation characterised by its sodium, calcium and potassium components and which are necessary for eliciting and maintaining the growth hormone release. Synergistic growth hormone release involves a mechanism other than a potentiated calcium influx and in short involves the integration of a complex array of intracellular events and pathways. A model is suggested which summarises the role of extracellular calcium in GH release from somatotroph cells of the domestic fowl integrating the regulatory mechanisms involved both at the membrane level and the intracellular level.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Central Lancashire

Year dc:date.issued

1993

Author dc:creator

• Robson, Helen

• C110 - Applied biology

Language dc:language

en