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K. R. VAN KAMPEN and L. C. ELLIS

SUMMARY

Prolonged gestation associated with cyclopia in offspring of ewes ingesting Veratrum californicum is described. In single or multiple pregnancies where all foetuses are cyclopic, foetal hypophysial aplasia, foetal thyroidal and adrenal hypoplasia, and foetal gonadal hypertrophy were associated with prolonged gestation. Cyclopic foetuses that were twins to normal foetuses were delivered at term and, with the exception of hypophysial aplasia, other endocrine organs (thyroid, adrenal and gonads) showed no morphologic abnormalities.

In sheep, during prolonged gestation, comparative studies of the ability of maternal and foetal endocrine glands to synthesize steroids indicated that the foetal ovary was capable of transforming more substrates (pregnenolone and progesterone) into steroid metabolites than the maternal ovary, even though the same group of metabolites is formed by foetal and maternal ovaries. Foetal adrenals produced more testosterone than maternal adrenals, but synthesized very little cortisol, corticosterone and cortisone. Foetal adrenals were incapable of forming water-soluble steroids although the ovaries from cyclopic foetuses and maternal adrenals possessed this capability.

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J. L. FREHN, R. L. URRY, and L. C. ELLIS

SUMMARY

Adult, male hamsters exposed to a photoperiod of 1 h light: 23 h darkness for either 2, 3, 4, 6, 8, or 10 weeks exhibited significantly lower testicular weights than did controls after 3 and 4 weeks of exposure to 14 h light: 10 h darkness. Liver Δ4-reductase activity was significantly decreased by 4 weeks of exposure to the short photoperiod. Exogenous melatonin decreased Δ4-reductase activity when incubated with either hamster liver (at 10−7 and 10−5 mol melatonin/l) or hamster hypothalamus (at 10−6 mol melatonin/l). In contrast, exogenous melatonin stimulated Δ4-reductase activity in preparations of rat liver (at 10−7 and 10−6 mol/l) and rat hypothalamus (at 10−9, 10−8, 10−7, and 10−6 mol/l). The possible role of melatonin in influencing the testosterone: dihydrotestosterone ratio is discussed in relation to possible regulation of gonadotrophin release.

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Juliane K Czeczor, Amanda J Genders, Kathryn Aston-Mourney, Timothy Connor, Liam G Hall, Kyoko Hasebe, Megan Ellis, Kirstie A De Jong, Darren C Henstridge, Peter J Meikle, Mark A Febbraio, Ken Walder, and Sean L McGee

The amyloid precursor protein (APP) generates a number of peptides when processed through different cleavage mechanisms, including the amyloid beta peptide that is implicated in the development of Alzheimer’s disease. It is well established that APP via its cleaved peptides regulates aspects of neuronal metabolism. Emerging evidence suggests that amyloidogenic processing of APP can lead to altered systemic metabolism, similar to that observed in metabolic disease states. In the present study, we investigated the effect of APP deficiency on obesity-induced alterations in systemic metabolism. Compared with WT littermates, APP-deficient mice were resistant to diet-induced obesity, which was linked to higher energy expenditure and lipid oxidation throughout the dark phase and was associated with increased spontaneous physical activity. Consistent with this lean phenotype, APP-deficient mice fed a high-fat diet (HFD) had normal insulin tolerance. However, despite normal insulin action, these mice were glucose intolerant, similar to WT mice fed a HFD. This was associated with reduced plasma insulin in the early phase of the glucose tolerance test. Analysis of the pancreas showed that APP was required to maintain normal islet and β-cell mass under high fat feeding conditions. These studies show that, in addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.