PubMed · 14936778
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M VOGT. 1952-02-15. [New developments in adrenal cortex physiology].. https://pubmed.ncbi.nlm.nih.gov/14936778/
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Previous studies have indicated that digoxin (DG) inhibits testosterone production by rat testicular interstitial cells through both in vivo and in vitro experiments. DG and digitoxin (DT), but not ouabain, inhibit the progesterone, pregnenolone, and corticosterone secretion by rat granulosa cells, luteal cells, and zona fasciculata-reticularis (ZFR) cells, respectively. However, the effect of DG and DT on the enzyme kinetics of cytochrome P450 side chain cleavage enzyme (P450scc), the protein expression of P450scc and steroidogenic acute regulatory protein (StAR), and mRNA expression of StAR are unclear. ZFR cells were prepared from adrenocortical tissues of ovariectomized rats, and then challenged with adrenocorticotropin (ACTH), 8-Br-cAMP, forskolin, A23187, cyclopiazonic acid (CPA), nicotinic acid adenine dinucleotide phosphate (NAADP), trilostane, 25-OH-Cholesterol, progesterone, or deoxycorticosterone in the presence of DG, DT, or ouabain for 1 h. Enzyme kinetics of P450scc, protein expression of acute regulatory protein (StAR) and P450scc, and mRNA expression of StAR were investigated. DG and DT but not ouabain suppressed basal and other evoked-corticosterone release significantly. DG and DT also inhibited pregnenolone production. The Vmax of the DG and DT group was the same as the control group, but the Km was higher in DG- and DT-treated group than in control group. DT and ouabain significant suppressed mRNA expression of StAR. DG and DT had no effect on the P450scc and StAR protein expression at basal state, but diminished ACTH-induced StAR protein expression to basal level. These results indicated that DG and DT have an inhibitory effect on corticosterone production via a Na+, K+-ATPase-independent mechanism by diminishing actions on cAMP-, Ca2+-pathway, competitive inhibition of P450scc enzyme and reduction of StAR mRNA expression.
The structure of the normal adrenal cortex is changed by stimulating hormones (ACTH) and inhibiting hormonal drugs (especially glucocorticoids). ACTH induces hyperplasia and lipid depletion in the fascicular and reticular zones, whereas glucocorticoids lead to atrophy and lipid accumulation in both zones. In animal experiments, the adrenostatic drug mitotane causes shrinkage of the cells of the fascicular and reticular zones, whereas metyrapone induces a decrease in the steroid producing organelle system and aminoglutethimide leads to an increase in lipids. In the therapy of patients with adrenocortical cancer, mitotane can cause an increase in of necrosis and fibrosis, but also in intracellular lipid. The ultrastructure shows increased liposomes, more pigment-rich lysosomes and laminated bodies.
Commercial sows are typically confined in crates before and during parturition and remain there throughout lactation. In various animal species including non-lactating pigs, confinement over similar periods leads to adaptive changes in the HPA axis, consistent with chronic stress. To investigate evidence for chronic stress in lactating sows, primiparous sows (gilts) were kept in behaviourally confining crates with straw bedding (CS, n = 8) or without bedding (C, n = 8) or in larger strawed pens (PS, n = 16) between 5 days before parturition until 29 days postpartum (piglets were weaned on day 28). Behavioural and physiological recordings (Plasma ACTH and cortisol) were taken at intervals (baseline), and CRH injections were given on five occasions (days 2, 8, 15, 22 and 29 postpartum). The PS gilts spent more time in substrate-directed behaviour and lying ventrally, and less time lying laterally and sitting than the two crated treatments (C and CS) throughout lactation. Baseline plasma ACTH and cortisol levels showed no treatment differences, although we confirmed that a diurnal pattern exists, with morning (1000 h) cortisol being higher than later in the day. CRH challenge tests suggested changes in the HPA axis, consistent with chronic stress, by the end of the lactation period. Cortisol response to CRH tended to be higher in CS than PS across all days, and by day 29 cortisol response to CRH was significantly higher in CS compared to PS and tended to be higher in C than PS. Cortisol/ACTH ratio following CRH challenge also tended to be higher in the crate treatments (C and CS) by day 29. These data suggest that prolonged confinement in farrowing crates may have a negative impact on sow welfare.