CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging.

The molecular causes of deteriorating oocyte quality during aging are poorly defined. Since oocyte developmental competence relies on post-transcriptional regulations, we tested whether defective mRNA translation contributes to this decline in quality. Disruption in ribosome loading on maternal transcripts is present in old oocytes. Using a candidate approach, we detect altered translation of 3'-UTR-reporters and altered poly(A) length of the endogenous mRNAs. mRNA polyadenylation depends on the cytoplasmic polyadenylation binding protein 1 (CPEB1). Cpeb1 mRNA translation and protein levels are decreased in old oocytes. This decrease causes de-repression of Ccnb1 translation in quiescent oocytes, premature CDK1 activation, and accelerated reentry into meiosis. De-repression of Ccnb1 is corrected by Cpeb1 mRNA injection in old oocytes. Oocyte-specific Cpeb1 haploinsufficiency in young oocytes recapitulates all the translation phenotypes of old oocytes. These findings demonstrate that a dysfunction in the oocyte translation program is associated with the decline in oocyte quality during aging.

Use of bioelectrical impedance analysis to determine body composition changes in HIV-associated wasting.

AIDS wasting syndrome results in loss of lean body mass and body cell mass. This 12-week, open-label study used bioelectrical impedance analysis to measure body composition changes in 24 patients with AIDS wasting syndrome receiving recombinant human growth hormone (r-hGH). The primary endpoint was percentage monthly change in body weight before/after r-hGH. Secondary endpoints included change from baseline in body composition (bioelectrical impedance analysis), isometric strength and CD4+ count. Twenty patients completed the study: r-hGH resulted in mean weight gains (+2.7%, P = 0.146), and significant increases in mean body cell mass (+8.0%, P = 0.0211), lean body mass (+4.8%, P = 0.0373) and water (+5.5%, P < 0.023). Body fat decreased throughout, but not significantly. r-hGH was generally well tolerated; the most frequent adverse events were fever (7.3%) and diarrhoea (6.3%). Thus, bioelectrical impedance analysis can detect improved body cell mass independent of changes in body weight resulting from r-hGH treatment in patients with AIDS wasting syndrome.

Pituitary Corticotroph Adenoma in a Woman with Long-Standing Addison's Disease: A Histologic, immunocytochemical, Electron Microscopic, and In Situ Hybridization Study.

A 64-year-old woman with long-standing Addison's disease owing to destructive immune adrenalitis presented with hyperpigmentation and progressively increasing blood adrenocorticotrophic hormone (ACTH) levels. Magnetic resonance imaging demonstrated a pituitary microadenoma, which was removed by transsphenoidal surgery and investigated by histology, immunocytochemistry, transmission electron microscopy, and in situ hybridization (ISH). The morphologic studies revealed a basophilic, periodic acid-Schift (PAS)-positive pituitary adenoma immunoreactive for ACTH and B-endorphin and in several cells for a-subunit. By transmission electron microscopy, the tumor was a densely granulated corticotroph adenoma, which, by ISH, expressed pro-opiomelanocortin (POMC) mRNA. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis was an intriguing finding. Corticotroph adenomas in patients with long-standing Addison's disease were very rarely examined by morphology. Our report includes a detailed morphologic analysis and is the first demonstration of POMC mRNA in the tumor cells using ISH. The question of whether the adenoma was related to increased secretory activity secondary to protracted hypocorticism or developed independently unrelated to deranged endocrine homeostasis remains unresolved. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis favors the interpretation that hypothalamic stimulation played no major role in adenoma formation in our case.