Interactive metabolic signatures of testicular testosterone with bilateral adrenalectomy in mice.

The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes have reciprocal relationships with steroidogenesis regulation. However, the relationship between testicular steroids and defective glucocorticoid production under chronic stress remains unclear. Metabolic changes of testicular steroids in bilateral adrenalectomized (bADX) 8-week-old C57BL/6 male mice were measured using gas chromatography-mass spectrometry. Twelve weeks after surgery, testis samples were obtained from the model mice, which were divided into tap-water (n = 12) and 1 % saline (n = 24) supplementation groups, and their testicular steroid levels were compared with those of sham controls (n = 11). An increased survival rate with lower testicular levels of tetrahydro-11-deoxycorticosterone was observed in the 1 % saline group compared to both the tap-water (p = 0.029) and sham (p = 0.062) groups. Testicular corticosterone levels were significantly decreased in both tap-water (4.22 ± 2.73 ng/g, p = 0.015) and 1 % saline (3.70 ± 1.69, p = 0.002) groups compared to those in sham controls (7.41 ± 7.39). Testicular testosterone levels tended to increase in both bADX groups compared to those in the sham controls. In addition, increased metabolic ratios of testosterone to androstenedione in tap-water (2.24 ± 0.44, p < 0.05) and 1 % saline (2.18 ± 0.60, p < 0.05) mice compared to sham controls (1.87 ± 0.55) suggested increased production of testicular testosterone. No significant differences in serum steroid levels were observed. Defective adrenal corticosterone secretion and increased testicular production in bADX models revealed an interactive mechanism underlying chronic stress. The present experimental evidence suggests the crosstalk between the HPA and HPG axes in homeostatic steroidogenesis.

Intronic Enhancer Is Essential for Nr5a1 Expression in the Pituitary Gonadotrope and for Postnatal Development of Male Reproductive Organs in a Mouse Model.

Nuclear receptor subfamily 5 group A member 1 (NR5A1) is expressed in the pituitary gonadotrope and regulates their differentiation. Although several regulatory regions were implicated in Nr5a1 gene expression in the pituitary gland, none of these regions have been verified using mouse models. Furthermore, the molecular functions of NR5A1 in the pituitary gonadotrope have not been fully elucidated. In the present study, we generated mice lacking the pituitary enhancer located in the 6th intron of the Nr5a1 gene. These mice showed pituitary gland-specific disappearance of NR5A1, confirming the functional importance of the enhancer. Enhancer-deleted male mice demonstrated no defects at fetal stages. Meanwhile, androgen production decreased markedly in adult, and postnatal development of reproductive organs, such as the seminal vesicle, prostate, and penis was severely impaired. We further performed transcriptomic analyses of the whole pituitary gland of the enhancer-deleted mice and controls, as well as gonadotropes isolated from Ad4BP-BAC-EGFP mice. These analyses identified several genes showing gonadotrope-specific, NR5A1-dependent expressions, such as Spp1, Tgfbr3l, Grem1, and Nr0b2. These factors are thought to function downstream of NR5A1 and play important roles in reproductive organ development through regulation of pituitary gonadotrope functions.

Unraveling the Origin and Mechanism of Nanofilament Formation in Polycrystalline SrTiO3 Resistive Switching Memories.

Three central themes in the study of the phenomenon of resistive switching are the nature of the conducting phase, why it forms, and how it forms. In this study, the answers to all three questions are provided by performing switching experiments in situ in a transmission electron microscope on thin films of the model system polycrystalline SrTiO3 . On the basis of high-resolution transmission electron microscopy, electron-energy-loss spectroscopy and in situ current-voltage measurements, the conducting phase is identified to be SrTi11 O20 . This phase is only observed at specific grain boundaries, and a Ruddlesden-Popper phase, Sr3 Ti2 O7 , is typically observed adjacent to the conducting phase. These results allow not only the proposal that filament formation in this system has a thermodynamic origin-it is driven by electrochemical polarization and the local oxygen activity in the film decreasing below a critical value-but also the deduction of a phase diagram for strongly reduced SrTiO3 . Furthermore, why many conducting filaments are nucleated at one electrode but only one filament wins the race to the opposite electrode is also explained. The work thus provides detailed insights into the origin and mechanisms of filament generation and rupture.