Thesis (M.S.)--University of Wisconsin--Madison, 1981. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 53-59).

Corticosterone and 20α dihydrocorticosterone have been found in the liver and blood of mice injected intravenously with C-11-dehydrocorticosterone. Within a few minutes after injection the latter is no longer detectable in the blood and liver, (1). The enzyme responsible for the reduction of the C-11 keto group has been isolated in the microsomal fraction of mouse liver homogenate. This fraction was precipitated by ultracentrifugation at 100,000 x G of the supernatant after centrifugation at 6,000 x G. NADPH₂ was established as the coenzyme required although limited activity could be demonstrated with NAD₂. The reaction can be reversed by use of NADP. Certain kinetic properties of the reaction have been investigated. The reaction velocity is proportional to enzyme concentration and linear with time over the period studied. For the reduction reaction with 11-dehydrocorticosterone as substrate Km = 1.8 x 10⁻⁵ and Vmax = 1.6 x 10⁻⁴ μmoles/ml/min. For the dehydrogenation reaction with corticosterone as substrate Km = 1.7 x 10⁻⁴ and Vmax = 2.7 x 10⁻³ μmoles/ml/min. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Thesis (Ph.D.) in Biological Sciences--University of Maine, 2007. / Includes vita. Includes bibliographical references (leaves 114-137).

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Both cortisol and corticosterone circulate in human plasma however corticosterone has been relatively neglected in human research to date. There is evidence of distinct regulation within different tissues with the transmembrane transporter ABCB1, highly expressed in the brain, exporting cortisol but not corticosterone. This may account for the relative accumulation of corticosterone in the CNS. In contrast, ABCC1, highly expressed in adipose tissue and skeletal muscle, exports corticosterone but not cortisol, suggesting cortisol is the principal glucocorticoid acting in these tissues. We tested the hypotheses that: (i) corticosterone physiology in humans is different to that of cortisol; (ii) inhibition of ABCC1 increases binding of corticosterone to corticosteroid receptors in adipose tissue and skeletal muscle but has no central CNS effect; and (iii) corticosterone is superior to cortisol as a basis for glucocorticoid replacement therapy with fewer metabolic side effects. We compared paired salivary and plasma samples from 10 healthy individuals. Plasma corticosterone showed a similar diurnal variation to cortisol but salivary corticosterone was low and did not correlate with plasma concentrations. A placebo-controlled randomised crossover study was carried out in 14 healthy individuals comparing receptor occupancy of glucocorticoids centrally and peripherally with and without ABCC1 inhibition. Receptor occupancy was assessed through displacement with MR and GR antagonists potassium canrenoate and mifepristone. Centrally, ABCC1 inhibition caused increased activation of the HPA axis after MR and GR antagonism. Peripherally, we were unable to show displacement from adipose tissue or skeletal muscle. A further placebo-controlled randomised crossover study is still ongoing in 16 patients with congenital adrenal hyperplasia, comparing metabolic effects of placebo, cortisol and corticosterone infusions over 6 hours. We present interim data for n=8. ACTH and 17-OHP were suppressed with corticosterone. Metabolic parameters were similar between placebo, cortisol and corticosterone phases. These data suggest corticosterone physiology is distinct compared with cortisol in humans. We have shown ABCC1 inhibition alters the HPA axis after receptor antagonism which suggests ABCC1 may play more of a key role centrally than previously thought. Corticosterone suppresses ACTH and 17-OHP in the short term in congenital adrenal hyperplasia, highlighting the possibility of its use as an alternative glucocorticoid replacement therapy in the future.

This study examined the number of conditioning trials necessary to produce associative nicotine tolerance and the changes in corticosterone levels during the procedures. Six independent groups of rats (N = 355) were run through tolerance acquisition procedures for 1, 5, or 10 conditioning sessions. Treatment groups were comprised of animals that received nicotine-environment pairings, animals that received nicotine explicitly unpaired with the drug administration environment, and control groups that received either saline throughout or no treatment. Three of the groups were tested for nicotine-induced analgesia using the tail-flick and hot-plate assays, and three groups were blood sampled after either nicotine or saline injection. Pairing of environment with nicotine produced greater tolerance for rats after 5 conditioning sessions in the tail flick and after 10 conditioning sessions in the hot-plate. Corticosterone levels were elevated in all rats given nicotine. Rats that received the nicotine-environment pairing showed a conditioned release of corticosterone in response the environment after both 5 and 10 conditioning sessions.

Thesis--Ph. D., University of Hong Kong, 1985.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

No description available.

This study examined the number of conditioning trials necessary to produce associative nicotine tolerance and the changes in corticosterone levels during the procedures. Six independent groups of rats (N = 355) were run through tolerance acquisition procedures for 1, 5, or 10 conditioning sessions. Treatment groups were comprised of animals that received nicotine-environment pairings, animals that received nicotine explicitly unpaired with the drug administration environment, and control groups that received either saline throughout or no treatment. Three of the groups were tested for nicotine-induced analgesia using the tail-flick and hot-plate assays, and three groups were blood sampled after either nicotine or saline injection. Pairing of environment with nicotine produced greater tolerance for rats after 5 conditioning sessions in the tail flick and after 10 conditioning sessions in the hot-plate. Corticosterone levels were elevated in all rats given nicotine. Rats that received the nicotine-environment pairing showed a conditioned release of corticosterone in response the environment after both 5 and 10 conditioning sessions.