Heterogeneity of Calcium Responses to Secretagogues in Corticotrophs From Male Rats.
Heterogeneity in homotypic cellular responses is an important feature of many biological systems, and it has been shown to be prominent in most anterior pituitary hormonal cell types. In this study, we analyze heterogeneity in the responses to hypothalamic secretagogues in the corticotroph cell population of adult male rats. Using the genetically encoded calcium indicator GCaMP6s, we determined the intracellular calcium responses of these cells to corticotropin-releasing hormone and arginine-vasopressin. Our experiments revealed marked population heterogeneity in the response to these peptides, in terms of amplitude and dynamics of the responses, as well as the sensitivity to different concentrations and duration of stimuli. However, repeated stimuli to the same cell produced remarkably consistent responses, indicating that these are deterministic on a cell-by-cell level. We also describe similar heterogeneity in the sensitivity of cells to inhibition by corticosterone. In summary, our results highlight a large degree of heterogeneity in the cellular mechanisms that govern corticotroph responses to their physiological stimuli; this could provide a mechanism to extend the dynamic range of the responses at the population level to allow adaptation to different physiological challenges.
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Nicola
N
Romanò
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Heather
H
McClafferty
Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter EX2 5DW, United Kingdom.|Engineering and Physical Sciences Research Council Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QJ, United Kingdom.|College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter EX4 4QF, United Kingdom.|Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom.
Jamie J
JJ
Walker
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Paul
P
Le Tissier
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Michael J
MJ
Shipston
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D052680:Corticotrophs / Q000187:drug effects* / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
D010908:Pituitary Hormones, Anterior; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D002118:Calcium; D003345:Corticosterone