Bone morphogenetic proteins (BMP)-4,-6, and-7 potently suppress basal and luteinizing hormone-induced androgen production by bovine theca interna cells in primary culture: Could ovarian hyperandrogenic dysfunction be caused by a defect in thecal BMP signaling?

We reported recently that bovine theca interna cells in primary culture express several type-I and type-II receptors for bone morphogenetic proteins (BMPs). The same cells express at least two potential ligands for these receptors (BMP-4 and - 7), whereas bovine granulosa cells and oocytes express BMP-6. Therefore, BMPs of intrafollicular origin may exert autocrine/paracrine actions to modulate theca cell function. Here we report that BMP-4, - 6, and - 7 potently suppress both basal ( P < 0.0001; respective IC50 values, 0.78, 0.30, and 1.50 ng/ml) and LH-induced ( P < 0.0001; respective IC50 values, 5.00, 0.55, and 4.55 ng/ml) androgen production by bovine theca cells while having only a moderate effect on progesterone production and cell number. Semiquantitative RT-PCR showed that all three BMPs markedly reduced steady-state levels of mRNA for P450c17. Levels of mRNA encoding steroidogenic acute regulatory protein, P450scc, and 3 beta-hydroxysteroid dehydrogenase were also reduced but to a much lesser extent. Immunocytochemistry confirmed a marked reduction in cellular content of P450c17 protein after BMP treatment ( P < 0.001). Exposure to BMPs led to cellular accumulation of phosphorylated Smad1, but not Smad2, confirming that the receptors signal via a Smad1 pathway. The specificity of the BMP response was further explored by coincubating cells with BMPs and several potential BMP antagonists, chordin, gremlin, and follistatin. Gremlin and chordin were found to be effective antagonists of BMP-4 and - 7, respectively, and the observation that both antagonists enhanced ( P < 0.01) androgen production in the absence of exogenous BMP suggests an autocrine/paracrine role for theca-derived BMP- 4 and - 7 in modulating androgen production. Collectively, these data indicate that an intrafollicular BMP signaling pathway contributes to the negative regulation of thecal androgen production and that ovarian hyperandrogenic dysfunction could be a result of a defective autoregulatory pathway involving thecal BMP signaling.

Mutamenti politico-istituzionali nella Venezia Giulia e a Trieste tra Tito e gli americani alla luce delle nuove testimonianze documentarie da Washington, 1944-1954

“La questione di Trieste”, ovvero la questione del confine italo-yugoslavo all’indomani della seconda guerra mondiale costituisce da lungo tempo oggetto di attenzione e di esame da parte della storiografia italiana e straniera. Con alcune importanti eccezioni, la ricostruzione complessiva di quelle vicende ha visto il più delle volte il prevalere di un approccio storico-diplomatico che ha reso difficile comprendere con chiarezza i rapporti e le interdipendenze fra contesto locale, contesto nazionale e contesto internazionale. Attraverso la lettura incrociata dell’ampia documentazione proveniente dai fondi dei National Archives Records Administration (NARA) questo studio tenta una rilettura delle varie fasi di sviluppo della questione nel periodo compreso tra il giugno del 1945 e l’ottobre del 1954 secondo una duplice prospettiva: nella prima parte si concentra sulla politica americana a Trieste, guardando nello specifico a due aspetti interni tra loro strettamente correlati, la gestione dell’ordine pubblico e la “strategia” del consenso da realizzarsi mediante il controllo dell’informazione da un lato e la promozione di una politica culturale dall’altro. Sono aspetti entrambi riconducibili al modello del direct rule, che conferiva al governo militare alleato (GMA) piena ed esclusiva autorità di governo sulla zona A della Venezia Giulia, e che ci appaiono centrali anche per cogliere l’interazione fra istituzioni e soggetti sociali. Nella seconda parte, invece, il modificarsi della fonte d’archivio indica un cambiamento di priorità nella politica estera americana relativa a Trieste: a margine dei negoziati internazionali, i documenti del fondo Clare Boothe Luce nelle carte dell’Ambasciata mostrano soprattutto come la questione di Trieste venne proiettata verso l’esterno, verso l’Italia in particolare, e sfruttata – principalmente dall’ambasciatrice – nell’ottica bipolare della guerra fredda per rinforzare il sostegno interno alla politica atlantica. Il saggio, dunque, si sviluppa lungo due linee: dentro e fuori Trieste, dentro 1945-1952, fuori 1953-1954, perché dalle fonti consultate sono queste ad emergere come aree di priorità nei due periodi. Abstract - English The “Trieste question”, or the question regarding the Italian - Yugoslav border after the Second World War, has been the object of careful examination in both Italian and foreign historiography for a long time. With a few important exceptions, the overall reconstruction of these events has been based for the most part on historic and diplomatic approaches, which have sometimes made it rather difficult to understand clearly the relationships and interdependences at play between local, national and international contexts. Through a comparative analysis of a large body of documents from the National Archives and Records Administration (NARA), College Park MD, this essay attempts a second reading of the various phases in which the question developed between June 1945 and October 1954, following a twofold perspective: the first part focuses on American policy for Trieste, specifically looking at two internal and closely linked aspects, on the one hand, the management of ‘law and order’, as well as a ‘strategy’ of consent, to be achieved through the control of all the means of information , and, on the other, the promotion of a cultural policy. Both aspects can be traced back to the ‘direct rule’ model, which gave the Allied Military Government (AMG) full and exclusive governing authority over Venezia Giulia’s Zone A. These issues are also fundamental to a better understanding of the relationships between institutions and social subjects. In the second part of the essay , the change in archival sources clearly indicates a new set of priorities in American foreign policy regarding Trieste: outside any international negotiations for the settlement of the question, the Clare Boothe Luce papers held in the Embassy’s archives, show how the Trieste question was focused on external concerns, Italy in particular, and exploited – above all by the ambassador – within the bi-polar optic of the Cold War, in order to strengthen internal support for Atlantic policies. The essay therefore follows two main lines of inquiry: within and outside Trieste, within in 1945-1952, and outside 1953-1954, since, from the archival sources used, these emerge as priority areas in the two periods.