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Title: The components of inheritance of adrenal corticosterone synthesis in mice
Author: Wood, Peter Rory Wells
ISNI:       0000 0001 3572 0057
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1982
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Relatively simple genetic models have been thought to explain differences between populations of man and rodent with respect to some endocrine functions. In the case of resting plasma corticosterone levels, differences between two mouse strains have been accounted for by a two-gene model. Genetic analysis of adrenal corticosteroidogenesis in the mouse, particularly in strains carrying aid (adrenal lipid depletion) genes, has been limited by the use of relatively insensitive techniques. In the present study, the in vitro corticosterone productive capacities of adrenals from 7-17 week old, male, DBA/2J, CBA/FaCam, C57BL/Tb and hybrid mice were measured using a specially modified existing rat isolated adrenal cell technique, permitting greater sensitivity of measurement to be achieved compared with previously used mouse adrenal slice techniques. Inter-experimental repeatability was high, except in cases where inhibition of steroidogenesis occurred due to the use of certain batches of bovine serum albumin (BSA). This protein was used in incubation media and it was found that batches of BSA with the greater amounts of protein impurities inhibited steroidogenesis the most. Although such inhibition was observed to affect ACTH responsiveness, it was absent when steroidogenesis was stimulated with dbcAMP, suggesting inhibition was exerted extra-cellularly. Corrections were made, on the basis of discernible degrees of inhibition by different batches of BSA, to provide estimates of steroidogenesis where experiments had been performed using inhibiting batches of serum albumin. Using cell suspensions prepared from adrenals pooled from genetically uniform animals, dose response studies indicated that a concentration of 2.5 mU ACTH/ml incubation medium was likely to produce maximal steroidogenic responses in all genotypes. A time-course study revealed that under conditions of maximal ACTH stimulation, cells of strain DBA/2J, which carry a gene causing adrenal lipid depletion, produced markedly less corticosterone with time compared with C57BL/Tb cells. It was speculated, from F?1(C57* x DBA) time-course values, that an interaction between time-dependent and time-independent characters might exist in this hybrid, signifying the existence of at least a two-gene difference between parental types. Pooled DBA/2J cells, unlike those of strain C57BL/Tb, possessed significantly reduced responses (about -10%) to ACTH compared to dbcAMP, indicating a relative inefficiency of the ACTH response in this strain. Means for the specified phenotype 'R' (pgms corticosterone produced/viable cell/hour in response to 2.5 mU/ml ACTH) were measured, using a number of pooled adrenal experiments, for parental and F? hybrid lines. Significant differences in mean R values were observed; strains C57BL/Tb and CBA/FaCam possessing mean values that were approximately 2.5X and 2X, respectively, the mean DBA/2J R value. The F1(C57 x DBA) possessed a mean R value that was significantly different from either parental type, whereas the F1(CBA x DBA) value was indistinguishable from that of strain CBA/CamFa* strain of dam given first in hybrid crosses. Investigation of corticosterone production by cells derived from individual adrenal pairs confirmed the strain differences observed for pooled organs and indicated the presence of stimulated and re-pressed classes of adrenal functional state within genetically uniform strains.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Genetics