Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

Behavioural and physiological responses of individually housed dairy calves to change in milk feeding frequency at different ages

peer reviewedThis study aimed to use a range of non-invasive monitoring technologies to investigate the behavioural and physiological responses of individually housed dairy calves to age at change in milk replacer (MR) feeding frequency. Forty-eight Holstein Friesian calves were individually penned and fed MR (625 g/d) as solids in one of three feeding regimes: (i) once-a-day feeding commencing at age 14 d (OAD14), (ii) once-a-day feeding commencing at age 28 d (OAD28) and (iii) twice-a-day feeding (TAD). Several behavioural (automatic activity sensors), physiological (infrared [IR] thermography and heart rate variability [HRV]) and haematological indicators were used to examine calf responses. Reduction in milk feeding frequency at 14 or 28 d of age increased daily concentrate intakes and drinking water consumption throughout the pre-wean period. Calf lying behaviour was unaffected by reduction in milk feeding frequency; however, TAD calves recorded a significant decrease in total daily lying time during the post-wean period compared with OAD28s. There was no effect of treatment on IR eye or rectal temperature throughout the experiment; however, there was an effect of age, with IR temperature decreasing as calf age increased. OAD14 calves tended to have decreased HRV at days 14 and 16, which is suggestive of an increased stress load. The findings suggest that under high levels of animal husbandry and whilst maintaining the same amount of milk powder/d (625 g/d), reduction in milk feeding frequency from twice to once daily at 28 d can occur without significant impact to behavioural, performance and physiological parameters assessed here

miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

The spindle assembly checkpoint (SAC) is a ‘wait-anaphase’ mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome–spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 – which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125

Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint

Hec1 contributes to accurate chromosome segregation by mediating spindle assembly checkpoint (SAC) signals and microtubule binding to ensure proper spindle assembly. We found that serine 165 of Hec1 was phosphorylated preferentially at kinetochores of misaligned chromosomes. This phosphorylation is important for SAC maintenance via Mad1/Mad2 localization to kinetochores